For attributes that represent a fraction or proportion. The former attribute type PCT for \"percentage\" is superceded by FRC and is no longer permitted. See also QTY.
. lincRNAs defined as following: A molecule of RNA 200-17000 nucleotides in length that is transcribed by non-protein coding areas of DNA. These ribonucleotides may play a role in a variety of biological processes.. human defined as following: Members of the species Homo sapiens.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. neoplasia defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. vertebrates defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes..", "label": "yes"} {"id": "converted_1145", "sentence1": "Could RG7112 be used as cancer therapy?", "sentence2": "RG7112 is a potent and selective member of the nutlin family of MDM2 antagonists currently in phase I clinical studies., Our findings offer a preclinical proof-of-concept that RG7112 is effective in treatment of solid tumors expressing wild-type p53., On the other hand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in early phases of trials in cancer patients., MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models., On the other hand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in early phases of trials in cancer patients., RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis., In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts., Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis., RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies., Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis, On the other hand, JNJ-26854165, a novel tryptamine derivative and RG7112, a cis-imidazoline representative have shown promising results in early phases of trials in cancer patients, RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis, MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models, In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts, RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies, We report a proof-of-mechanism study of RG7112, a small-molecule MDM2 antagonist, in patients with chemotherapy-naive primary or relapsed well-differentiated or dedifferentiated MDM2-amplified liposarcoma who were eligible for resection, BACKGROUND: RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis. RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies. , Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis. , Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study., RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies. , Thus, inhibitors of p53-MDM2 binding that can reactivate p53 in cancer cells may offer an effective approach for cancer therapy., Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis. RG7112 showed potent antitumor activity against a panel of solid tumor cell lines., A crystal structure of the RG7112-MDM2 complex revealed that the small molecule binds in the p53 pocket of MDM2, mimicking the interactions of critical p53 amino acid residues. Treatment of cancer cells expressing wild-type p53 with RG7112 activated the p53 pathway, leading to cell-cycle arrest and apoptosis., RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2. In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts., RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies. RG7112 and its inactive enantiomer RG7112i were evaluated against the 23 cell lines of the PPTP in vitro panel using 96 hours exposure (1 nM to 10 µM)., Thus, inhibitors of p53-MDM2 binding that can reactivate p53 in cancer cells may offer an effective approach for cancer therapy. RG7112 is a potent and selective member of the nutlin family of MDM2 antagonists currently in phase I clinical studies., In cancer cells expressing wild-type p53, RG7112 stabilizes p53 and activates the p53 pathway, leading to cell cycle arrest, apoptosis, and inhibition or regression of human tumor xenografts. ., Restoration of p53 activity by inhibiting the p53-MDM2 interaction may represent a novel approach to cancer treatment. RG7112 (2g) is the first clinical small-molecule MDM2 inhibitor designed to occupy the p53-binding pocket of MDM2., RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies.RG7112 and its inactive enantiomer RG7112i were evaluated against the 23 cell lines of the PPTP in vitro panel using 96 hours exposure (1 nM to 10 µM)., Notably, RG7112 was highly synergistic with androgen deprivation in LNCaP xenograft tumors. Our findings offer a preclinical proof-of-concept that RG7112 is effective in treatment of solid tumors expressing wild-type p53., RG7112 induced tumor regressions in solid tumors from different histotype panels, and exhibited consistent high-level activity against ALL xenografts. This high level of activity supports prioritization of RG7112 for further evaluation., RG7112 is a selective inhibitor of p53-MDM2 binding that frees p53 from negative control, activating the p53 pathway in cancer cells leading to cell cycle arrest and apoptosis. RG7112 was selected for evaluation by the Pediatric Preclinical Testing Program (PPTP) due to the relatively low incidence of p53 mutations in pediatric cancers compared with adult malignancies.[SEP]Relations: Protein S human has relations: drug_drug with Rituximab, drug_drug with Rituximab, drug_drug with Bamet-UD2, drug_drug with Bamet-UD2, drug_drug with Methotrexate, drug_drug with Methotrexate, drug_drug with Bortezomib, drug_drug with Bortezomib, drug_drug with NS-398, drug_drug with NS-398. Definitions: MDM2 defined as following: E3 ubiquitin-protein ligase Mdm2 (491 aa, ~55 kDa) is encoded by the human MDM2 gene. This protein is involved in the mediation of the ubiquitination and degradation of protein substrates, and the inhibition of apoptosis induction that is mediated by cellular tumor antigen p53.. liposarcoma defined as following: A malignant tumor derived from primitive or embryonal lipoblastic cells. It may be composed of well-differentiated fat cells or may be dedifferentiated: myxoid (LIPOSARCOMA, MYXOID), round-celled, or pleomorphic, usually in association with a rich network of capillaries. Recurrences are common and dedifferentiated liposarcomas metastasize to the lungs or serosal surfaces. (From Dorland, 27th ed; Stedman, 25th ed). p53 defined as following: Human TP53 wild-type allele is located in the vicinity of 17p13.1 and is approximately 19 kb in length. This allele, which encodes cellular tumor antigen p53 protein, plays a role in cell cycle regulation during the G0/G1transition. Alterations of the TP53 gene occur as both somatic and germline mutations in human malignancies in select cancer-prone families with Li-Fraumeni syndrome.. cancer cells defined as following: Cells of, or derived from, a malignant tumor.. malignancies defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. cell lines defined as following: Established cell cultures that have the potential to propagate indefinitely.. solid tumors defined as following: A benign or malignant neoplasm arising from tissues that do not include fluid areas. Representative examples include epithelial neoplasms (e.g. lung carcinoma, prostate carcinoma, breast carcinoma, colon carcinoma), and neoplasms arising from the soft tissues and bones (e.g. leiomyosarcoma, liposarcoma, chondrosarcoma, osteosarcoma). Neoplasms originating from the blood or bone marrow (leukemias and myeloproliferative disorders) are not considered solid tumors.. human defined as following: Members of the species Homo sapiens..", "label": "yes"} {"id": "converted_1281", "sentence1": "Is TNNI3K a cardiac-specific protein?", "sentence2": "cardiomyocyte-specific kinase TNNI3K , We report that cardiac troponin I-interacting kinase (TNNI3K), a cardiomyocyte-specific kinase,, TNNI3K, a cardiac-specific kinase, , The cardiac troponin I-interacting kinase (TNNI3K), a novel cardiac specific kinase, is associated with cardiomyocyte hypertrophy, Human cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific functional kinase that can bind to cTnI in a yeast two-hybrid screen. , Overexpression of TNNI3K, a cardiac-specific MAPKKK, promotes cardiac dysfunctio, Cardiac troponin I-interacting kinase (TNNI3K) is a cardiac-specific kinase whose biological function remains largely unknown, Cardiac troponin I-interacting kinase (TNNI3K) is a novel cardiac-specific kinase gene, a novel cardiac-specific kinase gene (TNNI3K),, TNNI3K is a novel cardiac troponin I-interacting kinase gene and its overexpression may promote cardiac myogenesis, , TNNI3K is a new cardiac-specific MAP kinase whose gene is localized to 1p31.1 and that belongs to a tyrosine kinase-like branch in the kinase tree of the human genome., The cardiac ankyrin repeat kinase (CARK) gene, also named TNNI3K for its interaction with cardiac troponin I, is both a unique expression and heart-enriched gene, Molecular cloning of cardiac troponin I-interacting kinase (TNNI3K), a novel cardiac-specific protein kinase containing seven N-terminal ankyrin (ANK) repeats followed by a protein kinase domain and a C-terminal Ser-rich domain, has previously been reported., TNNI3K is highly expressed in heart, but is undetectable in other tissues. Immunohistochemical analysis predominantly localized TNNI3K in the nucleus of cardiac myocytes. [SEP]Relations: TNNI3K has relations: protein_protein with TNNI3, protein_protein with TNNI3, anatomy_protein_present with heart, anatomy_protein_present with heart, protein_protein with NFATC3, protein_protein with NFATC3, protein_protein with ACTC1, protein_protein with ACTC1, protein_protein with HADHB, protein_protein with HADHB. Definitions: gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. cTnI defined as following: Troponin I, cardiac muscle (210 aa, ~24 kDa) is encoded by the human TNNI3 gene. This protein is involved in muscle filament movement in cardiac cells.. cardiac myocytes defined as following: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).. yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. Human defined as following: Members of the species Homo sapiens.. 1p31.1 defined as following: A chromosome band present on 1p.. repeats defined as following: Make or do or perform again..", "label": "yes"} {"id": "converted_3234", "sentence1": "Anaplasma phagocytophilum is an obligate gram-negative, intracellular bacterium, yes or no", "sentence2": "The genus Anaplasma belonging to the Anaplasmataceae family (order Rickettsiales) comprises obligate intracellular Gram-negative bacteria of veterinary and public health importance. Six species and five types of strains genetically related are currently assigned to the genus Anaplasma including Anaplasma marginale, A. centrale, A. bovis, A. phagocytophilum, A. ovis and A. platys as classified species, and \"A. capra\", A. odocolei sp. nov., Human granulocytic anaplasmosis (HGA), an increasingly recognized febrile tick-borne illness, is caused by a gram-negative obligate intracellular bacterium Anaplasma phagocytophilum[SEP]Relations: human anaplasmosis has relations: disease_disease with anaplasmosis, disease_disease with anaplasmosis. Anal margin neoplasm has relations: phenotype_phenotype with Anal margin squamous cell carcinoma, phenotype_phenotype with Anal margin squamous cell carcinoma, phenotype_phenotype with Anal margin melanoma, phenotype_phenotype with Anal margin melanoma, phenotype_phenotype with Anal margin basal cell carcinoma, phenotype_phenotype with Anal margin basal cell carcinoma, phenotype_phenotype with Abnormality of the anus, phenotype_phenotype with Abnormality of the anus. Definitions: Anaplasma marginale defined as following: A species of gram-negative bacteria and causative agent of severe bovine ANAPLASMOSIS. It is the most pathogenic of the ANAPLASMA species.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts..", "label": "yes"} {"id": "converted_4629", "sentence1": "Is covid-19 induced anosmia caused by disruption of nuclear architecture?", "sentence2": "Disruption of nuclear architecture as a cause of COVID-19 induced anosmia., Here, using molecular evaluation of human olfactory epithelium (OE) from subjects succumbing to COVID-19 and a hamster model of SARS-CoV-2 infection, we discovered widespread downregulation of olfactory receptors (ORs) as well as key components of their signaling pathway. OR downregulation likely represents a non-cell autonomous effect, since SARS-CoV-2 detection in OSNs is extremely rare both in human and hamster OEs. A likely explanation for the reduction of OR transcription is the striking reorganization of nuclear architecture observed in the OSN lineage, which disrupts multi-chromosomal compartments regulating OR expression in humans and hamsters. Our experiments uncover a novel molecular mechanism by which a virus with a very selective tropism can elicit persistent transcriptional changes in cells that evade it, contributing to the severity of COVID-19.[SEP]Relations: olfactory receptor activity has relations: molfunc_protein with OR2M7, molfunc_protein with OR2M7, molfunc_protein with OR2L13, molfunc_protein with OR2L13, molfunc_protein with OR2A7, molfunc_protein with OR2A7. colitis (disease) has relations: disease_protein with NOS2, disease_protein with NOS2, disease_protein with IL17A, disease_protein with IL17A. Definitions: anosmia defined as following: Inability to smell.. humans defined as following: Members of the species Homo sapiens.. ORs defined as following: An aqueous solution composed of glucose and electrolytes, including sodium, potassium, chloride, magnesium, and phosphorus, with dehydration preventative and rehydration activities. Upon oral administration of the oral rehydration solution (ORS), water, electrolytes and glucose are absorbed from the gastrointestinal (GI) tract into the systemic circulation. This replenishes the body's supply of water, carbohydrates and electrolytes, and prevents both dehydration and renal dysfunction.. olfactory receptors defined as following: Neurons in the OLFACTORY EPITHELIUM with proteins (RECEPTORS, ODORANT) that bind, and thus detect, odorants. These neurons send their DENDRITES to the surface of the epithelium with the odorant receptors residing in the apical non-motile cilia. Their unmyelinated AXONS synapse in the OLFACTORY BULB of the BRAIN.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. virus defined as following: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells.. SARS-CoV-2 infection defined as following: A viral disorder generally characterized by high FEVER; COUGH; DYSPNEA; CHILLS; PERSISTENT TREMOR; MUSCLE PAIN; HEADACHE; SORE THROAT; a new loss of taste and/or smell (see AGEUSIA and ANOSMIA) and other symptoms of a VIRAL PNEUMONIA. In severe cases, a myriad of coagulopathy associated symptoms often correlating with COVID-19 severity is seen (e.g., BLOOD COAGULATION; THROMBOSIS; ACUTE RESPIRATORY DISTRESS SYNDROME; SEIZURES; HEART ATTACK; STROKE; multiple CEREBRAL INFARCTIONS; KIDNEY FAILURE; catastrophic ANTIPHOSPHOLIPID ANTIBODY SYNDROME and/or DISSEMINATED INTRAVASCULAR COAGULATION). In younger patients, rare inflammatory syndromes are sometimes associated with COVID-19 (e.g., atypical KAWASAKI SYNDROME; TOXIC SHOCK SYNDROME; pediatric multisystem inflammatory disease; and CYTOKINE STORM SYNDROME). A coronavirus, SARS-CoV-2, in the genus BETACORONAVIRUS is the causative agent..", "label": "yes"} {"id": "converted_1563", "sentence1": "Are cyclophilins ubiquitously expressed?", "sentence2": "Cyclophilin from Leishmania donovani (LdCyp) is a ubiquitous peptidyl-prolyl cis-trans isomerase, Cyclophilins (CYPs) and FK506-binding proteins (FKBPs) are ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) family., However, their wide distribution and ubiquitous nature signifies their fundamental importance in plant survival., Cyclophilins (Cyps) are ubiquitous proteins that effect the cis-trans isomerization of Pro amide bonds, and are thus crucial to protein folding., FK506 binding proteins (FKBPs) and cyclophilins (CYPs) are abundant and ubiquitous proteins belonging to the peptidyl-prolyl cis/trans isomerase (PPIase) superfamily, which regulate much of metabolism through a chaperone or an isomerization of proline residues during protein folding., Cyclophilin is a ubiquitous peptidyl prolyl cis/trans isomerase that plays critical roles in many biological processes., The receptor for cyclosporin is the protein cyclophilin, which is a ubiquitous peptidylprolyl isomerase. , Cyps (cyclophilins) are ubiquitous proteins of the immunophilin superfamily with proposed functions in protein folding, protein degradation, stress response and signal transduction. , Cyclophilins are folding helper enzymes belonging to the class of peptidyl-prolyl cis-trans isomerases (PPIases; EC 5.2.1.8) that catalyze the cis-trans isomerization of peptidyl-prolyl bonds in proteins. They are ubiquitous proteins present in almost all living organisms analyzed to date, with extremely rare exceptions., Immunophilins are ubiquitous enzymes responsible for proline isomerisation during protein synthesis and for the chaperoning of several membrane proteins., Cyclophilins (CyPs) are a large class of highly conserved ubiquitous peptidyl-prolyl cis-trans isomerases., Cyclophilins belong to the family of peptidyl-prolyl cis/trans isomerases (PPIases), which are ubiquitous and highly conserved enzymes capable of cis/trans isomerizing Xaa-Pro peptide bonds. , Originally identified as the cellular targets of immunosuppressant drugs, the immunophilins encompass two ubiquitous protein families: the FK-506 binding proteins or FKBPs, and the cyclosporin-binding proteins or cyclophilins.[SEP]Relations: Cyclosporine has relations: drug_drug with Gatifloxacin, drug_drug with Gatifloxacin, drug_drug with Etoposide, drug_drug with Etoposide, drug_drug with Genistein, drug_drug with Genistein, drug_drug with Hypericin, drug_drug with Hypericin, drug_drug with Alogliptin, drug_drug with Alogliptin. Definitions: isomerases defined as following: A class of enzymes that catalyze geometric or structural changes within a molecule to form a single product. The reactions do not involve a net change in the concentrations of compounds other than the substrate and the product.(from Dorland, 28th ed) EC 5.. immunophilins defined as following: Members of a family of highly conserved proteins which are all cis-trans peptidyl-prolyl isomerases (PEPTIDYLPROLYL ISOMERASE). They bind the immunosuppressant drugs CYCLOSPORINE; TACROLIMUS and SIROLIMUS. They possess rotamase activity, which is inhibited by the immunosuppressant drugs that bind to them.. cyclosporin defined as following: A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).. Cyclophilins defined as following: A family of peptidyl-prolyl cis-trans isomerases that bind to CYCLOSPORINS and regulate the IMMUNE SYSTEM. EC 5.2.1.-. membrane proteins defined as following: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. FK506-binding proteins defined as following: A family of immunophilin proteins that bind to the immunosuppressive drugs TACROLIMUS (also known as FK506) and SIROLIMUS.. immunophilin defined as following: An enzyme that catalyzes the isomerization of proline residues within proteins. EC 5.2.1.8.. organisms defined as following: A living entity.. cyclophilins defined as following: A family of peptidyl-prolyl cis-trans isomerases that bind to CYCLOSPORINS and regulate the IMMUNE SYSTEM. EC 5.2.1.-.", "label": "yes"} {"id": "converted_3479", "sentence1": "Is modified vaccinia Ankara effective for smallpox?", "sentence2": "BACKGROUND: Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. , The three MVA lots induced equivalent antibody titers two weeks after the second vaccination, with seroconversion rates of 99·8% (PRNT) and 99·7% (ELISA). , INTRODUCTION: To guide the use of modified vaccinia Ankara (MVA) vaccine in response to a release of smallpox virus, the immunogenicity and safety of shorter vaccination intervals, and administration by jet injector (JI), were compared to the standard schedule of administration on Days 1 and 29 by syringe and needle (S&N)., Erratum: Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial., Modified vaccinia Ankara virus (MVA) is a smallpox vaccine candidate. , A Randomized, Double-Blind, Placebo-Controlled Phase II Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects., BACKGROUND: Modified Vaccinia Ankara MVA-BN® is a live, highly attenuated, viral vaccine under advanced development as a non-replicating smallpox vaccine. , CONCLUSIONS: One or two doses of MVA were safe and immunogenic in a 56-80 years old vaccinia-experienced population. , The results suggest that a single dose of MVA in a 56-80 years old population was well tolerated and sufficient to rapidly boost the long-term B cell memory response induced by a prior vaccination with a traditional smallpox vaccine., Modified Vaccinia Ankara (MVA) poxvirus has been assessed for cardiac safety in a large placebo-controlled clinical trial., BACKGROUND: Modified vaccinia Ankara (MVA) is being developed as a safer smallpox vaccine and is being placed in the US Strategic National Stockpile (SNS) as a liquid formulation for subcutaneous (SC) administration at a dose of 1×10(8) TCID50 in a volume of 0.5mL. , IMVAMUNE, an attenuated modified vaccinia Ankara virus vaccine for smallpox infection., Bavarian Nordic is developing IMVAMUNE, which is based on a live attenuated modified vaccinia Ankara virus, for the potential prevention of smallpox infection, particularly in those patients contraindicated to traditional smallpox vaccines, such as the immunocompromised and those with eczema or dermatitis., IMVAMUNE: modified vaccinia Ankara strain as an attenuated smallpox vaccine., Modified vaccinia Ankara: potential as an alternative smallpox vaccine., Evaluation of modified vaccinia virus Ankara as an alternative vaccine against smallpox in chronically HIV type 1-infected individuals undergoing HAART., Modified vaccinia Ankara: potential as an alternative smallpox vaccine, Modified vaccinia Ankara ( MVA ) is being developed as a safer smallpox vaccine and is being placed in the US Strategic National Stockpile ( SNS ) as a liquid formulation for subcutaneous ( SC ) administration at a dose of 1×10 ( 8 ) TCID50 in a volume of 0.5mL, Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations, Bavarian Nordic is developing IMVAMUNE , which is based on a live attenuated modified vaccinia Ankara virus , for the potential prevention of smallpox infection , particularly in those patients contraindicated to traditional smallpox vaccines , such as the immunocompromised and those with eczema or dermatitis, One of the most advanced and most promising vectors is the attenuated , non-replicating poxvirus MVA ( modified vaccinia virus Ankara) , a safer derivative of the uniquely successful smallpox vaccine, Modified vaccinia virus Ankara ( MVA ) is a highly attenuated vaccinia virus that is under consideration as an alternative to the conventional smallpox vaccine Dryvax, Modified Vaccinia virus Ankara ( MVA ) is an attenuated derivative , also used in the smallpox eradication campaign and now being developed as a recombinant viral vector to produce vaccines against infectious diseases and cancer, While modified vaccinia virus Ankara ( MVA ) is currently in clinical development as a safe vaccine against smallpox and heterologous infectious diseases , its immunogenicity is likely limited due to the inability of the virus to replicate productively in mammalian hosts, Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations., Modified Vaccinia virus Ankara (MVA) is a replication-deficient and attenuated derivative, also used in the smallpox eradication campaign and now being developed as a recombinant viral vector to produce vaccines against infectious diseases and cancer., Modified vaccinia Ankara was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations.[SEP]Relations: vaccinia has relations: disease_disease with infectious disease, disease_disease with infectious disease. Eczema has relations: drug_effect with Darunavir, drug_effect with Darunavir, drug_effect with Insulin detemir, drug_effect with Insulin detemir, drug_effect with Fluticasone, drug_effect with Fluticasone, drug_effect with Maraviroc, drug_effect with Maraviroc. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. dermatitis defined as following: Any inflammation of the skin.. infectious diseases defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. vaccinia virus defined as following: The type species of ORTHOPOXVIRUS, related to COWPOX VIRUS, but whose true origin is unknown. It has been used as a live vaccine against SMALLPOX. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of VACCINIA VIRUS.. viral vector defined as following: A viral gene transduction agent used to transfer genes or genetic materials, such as retroviruses and adenoviruses.. antibody defined as following: A protein complex that in its canonical form is composed of two identical immunoglobulin heavy chains and two identical immunoglobulin light chains, held together by disulfide bonds and sometimes complexed with additional proteins. An immunoglobulin complex may be embedded in the plasma membrane or present in the extracellular space, in mucosal areas or other tissues, or circulating in the blood or lymph. [GOC:add, GOC:jl, ISBN:0781765196]. HAART defined as following: Drug regimens, for patients with HIV INFECTIONS, that aggressively suppress HIV replication. The regimens usually involve administration of three or more different drugs including a protease inhibitor.. virus defined as following: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells.. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. vaccines defined as following: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases.. eczema defined as following: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed).. HIV defined as following: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS)..", "label": "yes"} {"id": "converted_2274", "sentence1": "Is autophagy modulated in a circadian fashion?", "sentence2": "TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in behavior and plasticity of L2 interneurons in the brain of Drosophila melanogaster., Our results indicate that the TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in the behavior and plasticity of neurons in the brain of adult flies., the pathways of autophagy, mTOR, SIRT1, and Wnt that control mammalian circadian rhythm, Metabolic pathways, bile acid synthesis, and autophagic and immune/inflammatory processes are driven by the biological clock. , our findings suggest that the clock geneBmal1is a positive regulator of autophagy through the mTOR signaling pathway and protects cardiomyocytes against high-glucose toxicity., Autophagy is a highly conserved intracellular degradation system, and recently was shown to display circadian rhythms in mice. [SEP]Relations: Protein S human has relations: drug_drug with Protocatechualdehyde, drug_drug with Protocatechualdehyde, drug_drug with Thalidomide, drug_drug with Thalidomide, drug_drug with Pargyline, drug_drug with Pargyline, drug_drug with Cephaloglycin, drug_drug with Cephaloglycin, drug_drug with Procarbazine, drug_drug with Procarbazine. Definitions: mTOR defined as following: Serine/threonine-protein kinase mTOR (2549 aa, ~289 kDa) is encoded by the human MTOR gene. This protein is involved in protein phosphorylation, signaling and cell growth.. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. TOR defined as following: Human RORC wild-type allele is located in the vicinity of 1q21 and is approximately 26 kb in length. This allele, which encodes nuclear receptor ROR-gamma protein, is involved in transcriptional activation.. interneurons defined as following: Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions.. cardiomyocytes defined as following: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. SIRT1 defined as following: A sirtuin family member found primarily in the CELL NUCLEUS. It is an NAD-dependent deacetylase with specificity towards HISTONES and a variety of proteins involved in gene regulation.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. flies defined as following: An order of the class Insecta. Wings, when present, number two and distinguish Diptera from other so-called flies, while the halteres, or reduced hindwings, separate Diptera from other insects with one pair of wings. The order includes the families Calliphoridae, Oestridae, Phoridae, SARCOPHAGIDAE, Scatophagidae, Sciaridae, SIMULIIDAE, Tabanidae, Therevidae, Trypetidae, CERATOPOGONIDAE; CHIRONOMIDAE; CULICIDAE; DROSOPHILIDAE; GLOSSINIDAE; MUSCIDAE; TEPHRITIDAE; and PSYCHODIDAE. The larval form of Diptera species are called maggots (see LARVA)..", "label": "yes"} {"id": "converted_4263", "sentence1": "Is FTY720 FDA approved?", "sentence2": "FTY720 (Fingolimod) is a known sphingosine-1-phosphate (S1P) receptor agonist that exerts strong anti-inflammatory effects and was approved as the first oral drug for the treatment of multiple sclerosis by the US Food and Drug Administration (FDA) in 2010. [SEP]Relations: Fingolimod has relations: drug_drug with WIN 55212-2, drug_drug with WIN 55212-2, drug_drug with G17DT, drug_drug with G17DT, drug_drug with Octreotide, drug_drug with Octreotide, drug_drug with mRNA-1273, drug_drug with mRNA-1273, drug_protein with S1PR5, drug_protein with S1PR5. Definitions: agonist defined as following: An agent that has affinity for a receptor and intrinsic activity at that receptor.. sphingosine-1-phosphate defined as following: A bioactive sphingolipid comprised of a sphingosine with a phosphate group attached to the carbon at position 1. Sphingosine 1-phosphate (S1P) binds to G protein-coupled S1P receptors (S1PRs) and initiates signaling pathways involved in the regulation of angiogenesis, the proliferation of skin cells, vascular stability and permeability, and T- and B-cell trafficking.. multiple sclerosis defined as following: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903). Fingolimod defined as following: An orally available derivate of myriocin and sphingosine-1-phosphate receptor 1 (S1PR1, S1P1) modulator, with potential anti-inflammatory and immunomodulating activities. Upon oral administration, fingolimod, as a structural analogue of sphingosine, selectively targets and binds to S1PR1 on lymphocytes and causes transient receptor activation followed by S1PR1 internalization and degradation. This results in the sequestration of lymphocytes in lymph nodes. By preventing egress of lymphocytes. fingolimod reduces both the amount of circulating peripheral lymphocytes and the infiltration of lymphocytes into target tissues. This prevents a lymphocyte-mediated immune response and may reduce inflammation. S1PR1, a G-protein coupled receptor, plays a key role in lymphocyte migration from lymphoid tissues. Fingolimod also shifts macrophages to an anti-inflammatory M2 phenotype, and modulates their proliferation, morphology, and cytokine release via inhibition of the transient receptor potential cation channel, subfamily M, member 7 (TRPM7)..", "label": "yes"} {"id": "converted_3707", "sentence1": "Has MLE4901 been tested in phase III clinical trials?", "sentence2": "METHODS\n\nThis phase 2, randomised, double-blind, placebo-controlled, single-centre, crossover trial assessed the effectiveness of an oral neurokinin 3 receptor antagonist (MLE4901) on menopausal hot flushes., Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial.[SEP]Definitions: Neurokinin 3 receptor defined as following: A class of cell surface receptors for tachykinins that prefers neurokinin B (neurokinin beta, neuromedin K) over other tachykinins. Neurokinin-3 (NK-3) receptors have been cloned and are members of the G-protein coupled receptor superfamily. They have been found in the central nervous system and in peripheral tissues..", "label": "no"} {"id": "converted_388", "sentence1": "Is there an association between borna virus and brain tumor?", "sentence2": "Borna disease virus (BDV), a nonsegmented, negative-strand RNA virus, infects a wide variety of mammalian species and readily establishes a long-lasting, persistent infection in brain cells. , To investigate the biological characteristics of field isolates of Borna disease virus (BDV), as well as to understand BDV infections outside endemic countries, we isolated the virus from brain samples of a heifer with Borna disease in Japan., Neonatal Borna disease virus (BDV) infection of the rat brain is associated with microglial activation and damage to the certain neuronal populations., In addition, compared to uninfected mixed cultures, activation of microglia in BDV-infected mixed cultures was associated with a significantly greater lipopolysaccharide-induced release of tumor necrosis factor alpha, interleukin 1beta, and interleukin 10. Taken together, the present data are the first in vitro evidence that persistent BDV infection of neurons and astrocytes rather than direct exposure to the virus or dying neurons is critical for activating microglia., Usually, Borna disease virus is not cleared from the brain but rather persists in neural cells., Varied persistent life cycles of Borna disease virus in a human oligodendroglioma cell line., Borna disease virus (BDV) establishes a persistent infection in the central nervous system of vertebrate animal species as well as in tissue cultures. , Thus, our findings show that BDV may have established a persistent infection at low levels of viral expression in OL cells with the possibility of a latent infection., These results suggested that BDV infection may cause direct damage in the developing brain by inhibiting the function of amphoterin due to binding by the p24 phosphoprotein., We describe a model for investigating disorders of central nervous system development based on neonatal rat infection with Borna disease virus, a neurotropic noncytolytic RNA virus. , Borna disease virus (BDV) replicates in brain cells. The neonatally infected rat with BDV exhibits developmental-neuromorphological abnormalities, neuronal cytolysis, and multiple behavioral and physiological alterations. , Borna disease virus (BDV) causes central nervous system (CNS) disease in several vertebrate species, which is frequently accompanied by behavioral abnormalities., Intrinsic responses to Borna disease virus infection of the central nervous system., Immune cells invading the central nervous system (CNS) in response to Borna disease virus (BDV) antigens are central to the pathogenesis of Borna disease (BD). , We report here the partial purification and characterization of cell-free BDV from the tissue culture supernatant of infected human neuroblastoma SKNSH cells., We have used the reverse transcriptase-polymerase chain reaction technique to gain insight into the pathogenesis of encephalitis caused by Borna disease virus (BDV). , In contrast, in the BDV-infected primary mixed cultures, we observed proliferation of microglia cells that acquired the round morphology and expressed major histocompatibility complex molecules of classes I and II.[SEP]Relations: borna disease has relations: disease_disease with viral infection of central nervous system, disease_disease with viral infection of central nervous system, disease_disease with encephalomyelitis, disease_disease with encephalomyelitis, disease_disease with Mononegavirales infectious disease, disease_disease with Mononegavirales infectious disease. encephalitis has relations: disease_disease with viral infection of central nervous system, disease_disease with viral infection of central nervous system, disease_disease with Hendra virus infection, disease_disease with Hendra virus infection. Definitions: neural cells defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. Borna disease defined as following: An encephalomyelitis of horses, sheep and cattle caused by BORNA DISEASE VIRUS.. microglia defined as following: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.. behavioral abnormalities defined as following: Troublesome or disruptive behavioral displays.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. tissue cultures defined as following: Originally the maintenance and growth of pieces of explanted tissue (plant or animal) in culture away from the source organism. Now usually refers to the (much more frequently used) technique of cell culture, using cells dispersed from tissues or distant descendants of such cells.. amphoterin defined as following: A 24-kDa HMGB protein that binds to and distorts the minor grove of DNA.. astrocytes defined as following: A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from \"star\" cells) are irregularly shaped with many long processes, including those with \"end feet\" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and \"reactive astrocytes\" (along with MICROGLIA) respond to injury.. interleukin 1beta defined as following: An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.. tumor necrosis factor alpha defined as following: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.. molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. brain cells defined as following: header term for the cells that make up the brain; includes neurons, glia, and other specialized cells in the brain.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. virus defined as following: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells.. infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. human defined as following: Members of the species Homo sapiens.. encephalitis defined as following: Inflammation of the BRAIN due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see ENCEPHALITIS, VIRAL) are a relatively frequent cause of this condition.. brain tumor defined as following: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain..", "label": "no"} {"id": "converted_3174", "sentence1": "Was stelara developed by Amgen?", "sentence2": "NICE does not specifically recommend switching from one biologic to another, and only ustekinumab (UST; STELARA®, Janssen Pharmaceuticals, Inc., Horsham, PA, USA) is recommended after anti-tumour necrosis factor failure.[SEP]Relations: Ustekinumab has relations: drug_drug with AMG 108, drug_drug with AMG 108, drug_drug with Imlifidase, drug_drug with Imlifidase, drug_drug with Eftrenonacog alfa, drug_drug with Eftrenonacog alfa, drug_drug with Esterified estrogens, drug_drug with Esterified estrogens, drug_drug with Leronlimab, drug_drug with Leronlimab. Definitions: Janssen Pharmaceuticals defined as following: A pharmaceutical company providing medicines for an array of health concerns in several therapeutic areas. The company conducts research and development into oncology, mental illness, neurological disorders, gastrointestinal disorders, fungal infection, and allergies.. NICE defined as following: An antimicrobial lock solution (ALS) containing the nitrate nitroglycerin, sodium citrate and ethanol, with potential antimicrobial and anticoagulant activities. Upon application to the catheter as an ALS, the nitroglycerin is converted into nitric oxide (NO), which exerts antimicrobial activity. The citrate exerts anticoagulant activity, thereby preventing blood clotting and occlusion and maintaining the fluidity of the administered solution. In addition, both citrate and ethanol exert antimicrobial activity. This may prevent bacterial colonization on the surface of the catheter, biofilm formation and prevents catheter-associated infections.. PA defined as following: A SI derived unit of pressure equivalent to one newton per square meter or 10 bars or to 1.45x10E-4 pounds per square inch.. UST defined as following: Any examination of software/hardware functionality that takes place outside of the developer's controlled environment..", "label": "no"} {"id": "converted_2790", "sentence1": "Is the PINES framework being used for the prediction of coding variants?", "sentence2": "PINES: phenotype-informed tissue weighting improves prediction of pathogenic noncoding variants., Here, we introduce the computational framework PINES (Phenotype-Informed Noncoding Element Scoring), which predicts the functional impact of noncoding variants by integrating epigenetic annotations in a phenotype-dependent manner. PINES enables analyses to be customized towards genomic annotations from cell types of the highest relevance given the phenotype of interest. We illustrate that PINES identifies functional noncoding variation more accurately than methods that do not use phenotype-weighted knowledge, while at the same time being flexible and easy to use via a dedicated web portal., Here, we introduce the computational framework PINES (Phenotype-Informed Noncoding Element Scoring), which predicts the functional impact of noncoding variants by integrating epigenetic annotations in a phenotype-dependent manner., We illustrate that PINES identifies functional noncoding variation more accurately than methods that do not use phenotype-weighted knowledge, while at the same time being flexible and easy to use via a dedicated web portal.Respond with exceptions, completions and modifications or revisions done before completion
. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm..", "label": "yes"} {"id": "converted_2327", "sentence1": "Is ACI-35 a passive vaccine?", "sentence2": "Two active vaccines targeting either nonphosphorylated (AAD-vac1) and phosphorylated tau (ACI-35) have entered Phase I testing.[SEP]", "label": "no"} {"id": "converted_3710", "sentence1": "Has ORMD-0801 been tested in patients?", "sentence2": "Glucose-reducing effect of the ORMD-0801 oral insulin preparation in patients with uncontrolled type 1 diabetes: a pilot study., In efforts to provide patients with a more compliable treatment method, Oramed Pharmaceuticals tested the capacity of its oral insulin capsule (ORMD-0801, 8 mg insulin) in addressing this resistant clinical state.[SEP]Definitions: insulin defined as following: A synthetic or animal-derived form of insulin used in the treatment of diabetes mellitus. Therapeutic insulin is formulated to be short-, intermediate- and long-acting in order to individualize an insulin regimen according to individual differences in glucose and insulin metabolism. Therapeutic insulin may be derived from porcine, bovine or recombinant sources. Endogenous human insulin, a pancreatic hormone composed of two polypeptide chains, is important for the normal metabolism of carbohydrates, proteins and fats and has anabolic effects on many types of tissues.. Pharmaceuticals defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances..", "label": "yes"} {"id": "converted_2970", "sentence1": "Does allele phasing improve the phylogenetic utility of ultraconserved elements?", "sentence2": "Allele Phasing Greatly Improves the Phylogenetic Utility of Ultraconserved Elements., Our empirical analyses of Ultraconserved Element (UCE) locus data collected from the South American hummingbird genus Topaza demonstrate that phased allele sequences carry sufficient phylogenetic information to infer the genetic structure, lineage divergence, and biogeographic history of a genus that diversified during the last three million years. The phylogenetic results support the recognition of two species, and suggest a high rate of gene flow across large distances of rainforest habitats but rare admixture across the Amazon River. Our simulations provide evidence that analyzing allele sequences leads to more accurate estimates of tree topology and divergence times than the more common approach of using contig sequences., Allele Phasing Greatly Improves the Phylogenetic Utility of Ultraconserved Elements.Advances in high-throughput sequencing techniques now allow relatively easy and affordable sequencing of large portions of the genome, even for nonmodel organisms. [SEP]Relations: male organism has relations: anatomy_anatomy with multicellular organism, anatomy_anatomy with multicellular organism. anatomical entity has relations: anatomy_anatomy with anatomical cluster, anatomy_anatomy with anatomical cluster, anatomy_anatomy with immaterial anatomical entity, anatomy_anatomy with immaterial anatomical entity, anatomy_anatomy with insect mouthpart, anatomy_anatomy with insect mouthpart, anatomy_anatomy with material anatomical entity, anatomy_anatomy with material anatomical entity. Definitions: locus defined as following: The position of a gene or a chromosomal marker on a chromosome; also, a stretch of DNA at a particular place on a particular chromosome. The use of locus is sometimes restricted to mean regions of DNA that are expressed.. organisms defined as following: A living entity.. genome defined as following: Anatomical set of genes in all the chromosomes.. Allele defined as following: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product..", "label": "yes"} {"id": "converted_2933", "sentence1": "Is there a deep-learning algorithm for protein solubility prediction?", "sentence2": "DeepSol: a deep learning framework for sequence-based protein solubility prediction., Protein solubility plays a vital role in pharmaceutical research and production yield. For a given protein, the extent of its solubility can represent the quality of its function, and is ultimately defined by its sequence. Thus, it is imperative to develop novel, highly accurate in silico sequence-based protein solubility predictors. In this work we propose, DeepSol, a novel Deep Learning-based protein solubility predictor. The backbone of our framework is a convolutional neural network that exploits k-mer structure and additional sequence and structural features extracted from the protein sequence., DeepSol: a deep learning framework for sequence-based protein solubility prediction.Deciduous maxillary right canine tooth; Universal designation C; ISO designation 53
. catalytic region defined as following: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction..", "label": "no"} {"id": "converted_4036", "sentence1": "Is colistin an antibiotic?", "sentence2": "all antibiotics tested, apart from colistin, , Among the selected antibiotics, there were 12 fluoroquinolone antibiotics (tosufloxacin, levofloxacin, sparfloxacin, clinafloxacin, pazufloxacin, gatifloxacin, enrofloxacin, lomefloxacin, norfloxacin, fleroxacin, flumequine, ciprofloxacin), 15 beta-lactam or cephalosporin antibiotics (cefmenoxime, cefotaxime, ceftizoxime, cefotiam, cefdinir, cefoperazone, cefpiramide, cefamandole, cefixime, ceftibuten, cefmetazole, cephalosporin C, aztreonam, piperacillintazobactam, mezlocillin), 3 tetracycline antibiotics (meclocycline, doxycycline, tetracycline), 2 membrane-acting agents (colistin and clofoctol),, Mice received an antibiotic cocktail (kanamycin, gentamicin, colistin, metronidazole, and vancomycin) for 96 h.[SEP]Relations: Colistin has relations: drug_drug with Ampicillin, drug_drug with Ampicillin, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Gentamicin, drug_drug with Gentamicin, drug_drug with Propicillin, drug_drug with Propicillin, drug_drug with Sultamicillin, drug_drug with Sultamicillin. Definitions: cefotaxime defined as following: Semisynthetic broad-spectrum cephalosporin.. ciprofloxacin defined as following: A broad-spectrum antimicrobial carboxyfluoroquinoline.. vancomycin defined as following: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to RISTOCETIN that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear.. beta-lactam defined as following: Four-membered cyclic AMIDES, best known for the PENICILLINS based on a bicyclo-thiazolidine, as well as the CEPHALOSPORINS based on a bicyclo-thiazine, and including monocyclic MONOBACTAMS. The BETA-LACTAMASES hydrolyze the beta lactam ring, accounting for BETA-LACTAM RESISTANCE of infective bacteria.. gentamicin defined as following: A complex of closely related aminoglycoside bases (e.g., Gentamicins C1, C2, and C1(subA)), obtained from MICROMONOSPORA purpurea and related species.. tetracycline antibiotics defined as following: Any of a group of broad spectrum naphthacene antibiotics isolated from various species of Streptomyces or produced semisynthetically. In bacteria, tetracycline antibiotics block binding of aminoacyl-tRNA to the mRNA-ribosome complex, thereby inhibiting protein synthesis. (NCI05). enrofloxacin defined as following: A fluoroquinolone antibacterial and antimycoplasma agent that is used in veterinary practice.. cefmenoxime defined as following: A cephalosporin antibiotic that is administered intravenously or intramuscularly. It is active against most common gram-positive and gram-negative microorganisms, is a potent inhibitor of Enterobacteriaceae, and is highly resistant to hydrolysis by beta-lactamases. The drug has a high rate of efficacy in many types of infection and to date no severe side effects have been noted.. doxycycline defined as following: A synthetic tetracycline derivative with similar antimicrobial activity.. colistin defined as following: Cyclic polypeptide antibiotic from Bacillus colistinus. It is composed of Polymyxins E1 and E2 (or Colistins A, B, and C) which act as detergents on cell membranes. Colistin is less toxic than Polymyxin B, but otherwise similar; the methanesulfonate is used orally.. kanamycin defined as following: The major component of the kanamycin complex, an aminoglycoside antibiotic isolated from Streptomyces kanamyceticus, with antibacterial activity.. lomefloxacin defined as following: A synthetic broad-spectrum fluoroquinolone with antibacterial activity. Lomefloxacin inhibits DNA gyrase, a type II topoisomerase involved in the induction or relaxation of supercoiling during DNA replication. This inhibition leads to a decrease in DNA synthesis during bacterial replication, resulting in cell growth inhibition and eventually cell lysis.. cefotiam defined as following: One of the CEPHALOSPORINS that has a broad spectrum of activity against both gram-positive and gram-negative microorganisms.. fleroxacin defined as following: A broad-spectrum antimicrobial fluoroquinolone. The drug strongly inhibits the DNA-supercoiling activity of DNA GYRASE.. gatifloxacin defined as following: A fluoroquinolone antibacterial agent and DNA TOPOISOMERASE II inhibitor that is used as an ophthalmic solution for the treatment of BACTERIAL CONJUNCTIVITIS.. cefixime defined as following: A third-generation cephalosporin antibiotic that is stable to hydrolysis by beta-lactamases.. sparfloxacin defined as following: A fluoroquinolone antibiotic that inhibits bacterial DNA gyrase, thereby inhibiting DNA replication and transcription. Sparfloxacin was withdrawn from the U.S. market due to a high incidence of phototoxicity.. ceftibuten defined as following: A semisynthetic, beta-lactamase-stable, third-generation cephalosporin with antibacterial activity. Ceftibuten binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.. cefdinir defined as following: A third-generation oral cephalosporin antibacterial agent that is used to treat bacterial infections of the respiratory tract and skin.. norfloxacin defined as following: A synthetic fluoroquinolone (FLUOROQUINOLONES) with broad-spectrum antibacterial activity against most gram-negative and gram-positive bacteria. Norfloxacin inhibits bacterial DNA GYRASE.. metronidazole defined as following: A nitroimidazole used to treat AMEBIASIS; VAGINITIS; TRICHOMONAS INFECTIONS; GIARDIASIS; ANAEROBIC BACTERIA; and TREPONEMAL INFECTIONS.. cefoperazone defined as following: Semisynthetic broad-spectrum cephalosporin with a tetrazolyl moiety that is resistant to beta-lactamase. It may be used to treat Pseudomonas infections.. ceftizoxime defined as following: A semisynthetic cephalosporin antibiotic which can be administered intravenously or by suppository. The drug is highly resistant to a broad spectrum of beta-lactamases and is active against a wide range of both aerobic and anaerobic gram-positive and gram-negative organisms. It has few side effects and is reported to be safe and effective in aged patients and in patients with hematologic disorders.. levofloxacin defined as following: The L-isomer of Ofloxacin.. clofoctol defined as following: A bacteriostatic antibiotic with activity against Gram-positive bacteria. Clofoctol is used in the treatment of upper and lower respiratory tract infections.. cefmetazole defined as following: A semisynthetic cephamycin antibiotic with a broad spectrum of activity against both gram-positive and gram-negative microorganisms. It has a high rate of efficacy in many types of infection and to date no severe side effects have been noted.. cefpiramide defined as following: A third-generation, semi-synthetic, beta-lactam cephalosporin antibiotic with antibacterial activity. Cefpiramide binds to penicillin-binding proteins (PBPs), transpeptidases that are responsible for crosslinking of peptidoglycan. By preventing crosslinking of peptidoglycan, cell wall integrity is lost and cell wall synthesis is halted.. aztreonam defined as following: A monocyclic beta-lactam antibiotic originally isolated from Chromobacterium violaceum. It is resistant to beta-lactamases and is used in gram-negative infections, especially of the meninges, bladder, and kidneys. It may cause a superinfection with gram-positive organisms.. cefamandole defined as following: Semisynthetic wide-spectrum cephalosporin with prolonged action, probably due to beta-lactamase resistance. It is used also as the nafate.. mezlocillin defined as following: Semisynthetic ampicillin-derived acylureido penicillin. It has been proposed for infections with certain anaerobes and may be useful in inner ear, bile, and CNS infections.. antibiotic defined as following: Substances naturally produced by microorganisms or their derivatives that selectively target microorganisms not humans. Antibiotics kill or inhibit the growth of microorganisms by targeting components of the microbial cell absent from human cells, including bacterial cell walls, cell membrane, and 30S or 50S ribosomal subunits. These substances are used in the treatment of bacterial and other microbial infections..", "label": "yes"} {"id": "converted_3070", "sentence1": "Are recessive coding variants responsible for the majority of undiagnosed nonconsanguineous individuals?", "sentence2": "Our results suggest that recessive coding variants account for a small fraction of currently undiagnosed nonconsanguineous individuals, and that the role of noncoding variants, incomplete penetrance, and polygenic mechanisms need further exploration.[SEP]", "label": "no"} {"id": "converted_2067", "sentence1": "Can glyburide reduce cerebral edema?", "sentence2": "Preclinical studies have shown that a continuous infusion of glyburide blocks edema formation and improves outcome. We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction., CONCLUSIONS: GAMES-RP was designed to provide critical information regarding glyburide for injection in patients with large hemispheric stroke and will inform the design of future studies., Glyburide is associated with attenuated vasogenic edema in stroke patients., Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4. , RESULTS: We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level.CONCLUSIONS: Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke. , Pilot study of intravenous glyburide in patients with a large ischemic stroke., BACKGROUND AND PURPOSE: Preclinical and retrospective clinical data indicate that glyburide, a selective inhibitor of sulfonylurea receptor 1-transient receptor potential melastatin 4, is effective in preventing edema and improving outcome after focal ischemia. , Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema., Glyburide in Treating Malignant Cerebral Edema. , Glyburide in Treating Malignant Cerebral Edema. Blocking Sulfonyl Urea One (SUR1) Receptors., The sulfonylurea receptor 1-regulated NC(Ca-ATP) channel is upregulated in rodent models of stroke with block of the channel by the sulfonylurea, glibenclamide (glyburide), significantly reducing mortality, cerebral edema, and infarct volume., Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema., In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema., Potential of glyburide to reduce intracerebral edema in brain metastases., Glyburide Advantage in Malignant Edema and Stroke (GAMES-RP) Trial: Rationale and Design., Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema., Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage., Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema, RESULTS: We report that IV glyburide was associated with T2 fluid-attenuated inversion recovery signal intensity ratio on brain MRI, diminished the lesional water diffusivity between days 1 and 2 (pseudo-normalization), and reduced blood MMP-9 level. , Preclinical data suggest that glyburide, an inhibitor of SUR1-TRPM4, is effective in preventing edema. , Exploratory analysis of glyburide as a novel therapy for preventing brain swelling., Inhibition of sulfonylurea receptor 1 (SUR1) by glyburide has been shown to decrease edema after subarachnoid hemorrhage. , In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema., Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema., Glyburide is reported to prevent brain swelling in preclinical rodent models of ischemic stroke through inhibition of a non-selective channel composed of sulfonylurea receptor 1 and transient receptor potential cation channel subfamily M member 4., Several surrogate markers of vasogenic edema appear to be reduced in the setting of IV glyburide treatment in human stroke., We hypothesize that treatment with RP-1127 (Glyburide for Injection) reduces formation of brain edema in patients after large anterior circulation infarction., Glyburide is a safe, inexpensive, and efficacious alternative to dexamethasone for the treatment of cerebral metastasis-related vasogenic edema.., Glyburide is associated with attenuated vasogenic edema in stroke patients.[SEP]Relations: Glyburide has relations: drug_effect with Edema, drug_effect with Edema, drug_effect with Hypoglycemia, drug_effect with Hypoglycemia. Cerebral edema has relations: drug_effect with Glycine betaine, drug_effect with Glycine betaine, drug_effect with Glatiramer, drug_effect with Glatiramer, drug_effect with Carmustine, drug_effect with Carmustine. Definitions: glyburide defined as following: An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide. malignancy defined as following: A malignant tumor at the original site of growth.. subarachnoid hemorrhage defined as following: Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.. dexamethasone defined as following: An anti-inflammatory 9-fluoro-glucocorticoid.. cerebral edema defined as following: Swelling due to an excessive accumulation of fluid in the brain.. human defined as following: Members of the species Homo sapiens.. ischemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue.. MMP-9 defined as following: An endopeptidase that is structurally similar to MATRIX METALLOPROTEINASE 2. It degrades GELATIN types I and V; COLLAGEN TYPE IV; and COLLAGEN TYPE V.. stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810). sulfonylurea defined as following: A class of compounds in which a sulfone functional group is attached to UREA.. sulfonylurea receptor 1 defined as following: ATP-BINDING CASSETTE PROTEINS that are highly conserved and widely expressed in nature. They form an integral part of the ATP-sensitive potassium channel complex which has two intracellular nucleotide folds that bind to sulfonylureas and their analogs..", "label": "yes"} {"id": "converted_285", "sentence1": "Is ospemifene effective for treatment of dyspareunia?", "sentence2": "Ospemifene, a novel selective estrogen receptor modulator, has been developed for the treatment of vulvovaginal atrophy and dyspareunia in postmenopausal women. , For the comparison of short-term ospemifene with placebo, parabasal cells (the standardized mean difference [SMD] = -37.5, 95% confidence interval [CI] = -41.83 to -33.17, P < 0.00001), superficial cells (SMD = 9.24, 95% CI = 7.70 to 10.79, P < 0.00001), vaginal PH (SMD = -0.89, 95% CI = -0.98 to -0.80, P = 0.00001), and dyspareunia (SMD = -0.37, 95% CI = -0.43 to -0.30, P = 0.00001) indicated that ospemifene was more effective than the placebo. , This meta-analysis indicates that ospemifene to be an effective and safe treatment for dyspareunia associated with postmenopausal vulvar and vaginal atrophy., Ospemifene is a selective estrogen receptor modulator (SERM), or estrogen receptor agonist/antagonist, that was recently approved by the US Food and Drug Administration for the treatment of dyspareunia associated with vulvar and vaginal atrophy, a chronic condition that affects up to 60% of postmenopausal women., In conclusion, ospemifene is a SERM with a unique estrogen agonist/antagonist tissue profile that was recently approved in the US for the treatment of dyspareunia associated with vulvar and vaginal atrophy in postmenopausal women. , To characterize the pharmacokinetics of the oral, non-estrogen agent ospemifene, an estrogen agonist/antagonist with tissue-selective effects (also called a selective estrogen receptor modulator) that was recently approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy in postmenopausal women., Here, we review the estrogen agonist/antagonist profile of ospemifene, a novel triphenylethylene derivative recently approved to treat dyspareunia, a symptom of vulvar and vaginal atrophy (VVA) due to menopause, both preclinically and clinically., Long-term studies on the endometrial safety of local estrogen and ospemifene are lacking. , Ospemifene is a tissue-selective estrogen agonist/antagonist (a selective estrogen receptor modulator) recently approved by the US Food and Drug Administration for treatment of dyspareunia, a symptom of VVA, due to menopause., SERMs with positive vaginal effects (such as improvement in the vaginal maturation index, reduced vaginal pH, and improvement in the signs and symptoms of VVA) on postmenopausal symptomatic women include lasofoxifene (clinical development on hold) and ospemifene, which was recently approved for the treatment of VVA-related dyspareunia, with a class effect warning of potential venous thrombosis risk. , Ospemifene is the first non-estrogen treatment approved for moderate to severe dyspareunia in women with menopause-related vulvar and vaginal atrophy. , This article summarizes the milestones in the development of ospemifene leading to this first approval for moderate to severe dyspareunia, a symptom of postmenopausal vulvar and vaginal atrophy., The aim of this work was to study the role of ospemifene, a novel selective estrogen receptor modulator, in the treatment of vulvar and vaginal atrophy in postmenopausal women with moderate to severe dyspareunia and physiological vaginal changes. , In this study, once-daily oral ospemifene 60 mg was effective for the treatment of vulvar and vaginal atrophy in postmenopausal women with dyspareunia., Clinical trials have confirmed that daily doses are well-tolerated and that it is effective in normalizing vaginal maturation index and pH as well as improving the symptoms associated with VVA including dyspareunia., Ospemifene was shown to be effective and well tolerated for the treatment of the symptoms of vaginal dryness and dyspareunia associated with vulvovaginal atrophy over and above the use of provided lubricants.[SEP]Relations: Ospemifene has relations: drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Orphenadrine, drug_drug with Orphenadrine, drug_drug with Amodiaquine, drug_drug with Amodiaquine. Dyspareunia has relations: drug_effect with Progesterone, drug_effect with Progesterone, drug_effect with Fluoxetine, drug_effect with Fluoxetine. Definitions: vaginal atrophy defined as following: A condition characterized by the absence of squamous maturation in the vaginal epithelium. It is associated with decreased estrogen production.. SERMs defined as following: A structurally diverse group of compounds distinguished from ESTROGENS by their ability to bind and activate ESTROGEN RECEPTORS but act as either an agonist or antagonist depending on the tissue type and hormonal milieu. They are classified as either first generation because they demonstrate estrogen agonist properties in the ENDOMETRIUM or second generation based on their patterns of tissue specificity. (Horm Res 1997;48:155-63). SMD defined as following: A heterogeneous group of disorders associated with walking and growth disturbances that become evident during the second year of life. Characteristics are platyspondyly (flattened vertebrae) and marked hip and knee metaphyseal lesions. The different forms of spondylometaphyseal dysplasia are distinguished by the localization and severity of involvement of the affected metaphyses.. venous thrombosis defined as following: The formation or presence of a blood clot (THROMBUS) within a vein.. lasofoxifene defined as following: A non-steroidal, naphthalene-derived, third-generation selective estrogen receptor modulator (SERM) with potential antineoplastic and anti-osteoporotic activities. Upon oral administration, lasofoxifene selectively binds to both estrogen receptor alpha (ERalpha; ESR1) and estrogen receptor beta (ERbeta; ESR2) with high affinity and mimics the effects of endogenous estradiol with varying agonist and antagonist effects in ER-expressing tissues. Blockade of ERalpha by lasofoxifene may potentially inhibit estrogen-dependent cancer cell proliferation in ER-expressing cancers. Lasofoxifene may also bind to the certain mutant forms of ERalpha, including the Y537S ESR1 mutant, making it potentially useful in the treatment of tumors that have acquired resistance to other ER-targeting agents.. vulvar defined as following: The external genitalia of the female. It includes the CLITORIS, the labia, the vestibule, and its glands.. estrogen receptor modulator defined as following: Substances that possess antiestrogenic actions but can also produce estrogenic effects as well. They act as complete or partial agonist or as antagonist. They can be either steroidal or nonsteroidal in structure.. dyspareunia defined as following: A question about whether an individual has or had painful intercourse.. vaginal dryness defined as following: An uncomfortable feeling of itching and burning in the vaginal opening resulting from inadequate vaginal lubrication. It is commonly seen during and after menopause, childbirth, or stressful conditions. It results in painful intercourse.. vulvovaginal atrophy defined as following: A condition associated with decreased estrogen production, characterized by dryness, inflammation, and itching of the vulva and vaginal tissues. It may also be associated with dysuria and dyspareunia..", "label": "yes"} {"id": "converted_2585", "sentence1": "Can CD55 deficiency cause thrombosis?", "sentence2": " The loss of CD55 and CD59 renders PNH erythrocytes susceptible to intravascular haemolysis, which can lead to thrombosis and to much of the morbidity and mortality of PNH. , CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis., CONCLUSIONS: CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55. , It is caused by the expansion of a hematopoietic progenitor cell that has acquired a mutation in the X-linked phosphatidylinositol glycan class A (PIGA) gene that results in deficiency of the glycosylphosphatidylinositol anchor structure responsible for fixing a wide spectrum of proteins particularly CD55 and CD59. The clinical features of this disease arise as a result of complement-mediated hemolysis in unprotected red cells, leukocytes, and platelets as well as the release of free hemoglobin. Patients may present with a variety of clinical manifestations, such as anemia, thrombosis, kidney disease, smooth muscle dystonias, abdominal pain, dyspnea, and extreme fatigue., The lack of one of the GPI-AP complement regulatory proteins (CD55, CD59) leads to hemolysis. The disease is diagnosed with hemolytic anemia, marrow failure and thrombosis., Paroxysmal nocturnal hemoglobinuria (PNH) is a rare bone marrow failure disorder that manifests with hemolytic anemia, thrombosis, and peripheral blood cytopenias. The absence of two glycosylphosphatidylinositol (GPI)-anchored proteins, CD55 and CD59, leads to uncontrolled complement activation that accounts for hemolysis and other PNH manifestations., RESULTS: CD55 and/or CD59 deficiencies were found in 1.6% (2/127) of patients with primary BCS, 1.0% (1/100) of non-malignant and non-cirrhotic patients with PVT, and 4.7% (4/85) of cirrhotic patients with PVT., Data of this study indicate that the PNH defect as detected with CD55, CD59, and CD16 is not an important cause of intra-abdominal thrombosis in northwestern India., PNH testing of red blood cells revealed a CD55 and CD59 deficiency consistent with PNH in both cases. The systemic complications typically associated with thrombosis were not observed for the following several months with early conservative treatments including eculizumab., Deficiency of the GPI-anchored complement inhibitors CD55 and CD59 on erythrocytes leads to intravascular hemolysis upon complement activation. Apart from hemolysis, another prominent feature is a highly increased risk of thrombosis., Genetic reconstitution of CD55 or treatment with a complement-inhibitory therapeutic antibody reversed abnormal complement activation.Respond with exceptions, completions and modifications or revisions done before completion
. motor neurons defined as following: Neurons which send impulses peripherally to activate muscles or secretory cells..", "label": "yes"} {"id": "converted_4070", "sentence1": "Is there a role for Dickkopf-1 (DKK1) in prostate cancer?", "sentence2": "Dickkopf-1 Can Lead to Immune Evasion in Metastatic Castration-Resistant Prostate Cancer., Metastatic castration-resistant prostate cancer (mCRPC) with low androgen receptor (AR) and without neuroendocrine signaling, termed double-negative prostate cancer (DNPC), is increasingly prevalent in patients treated with AR signaling inhibitors and is in need of new biomarkers and therapeutic targets.METHODS: Candidate genes enriched in DNPC were determined using differential gene expression analysis of discovery and validation cohorts of mCRPC biopsies. Laboratory studies were carried out in human mCRPC organoid cultures, prostate cancer (PCa) cell lines, and mouse xenograft models. Epigenetic studies were carried out in a rapid autopsy cohort.RESULTS: Dickkopf-1 (DKK1) expression is increased in DNPC relative to prostate-specific antigen (PSA)-expressing mCRPC in the Stand Up to Cancer/Prostate Cancer Foundation discovery cohort (11.2 v 0.28 reads per kilobase per million mapped reads; q < 0.05; n = 117) and in the University of Washington/Fred Hutchinson Cancer Research Center cohort (9.2 v 0.99 fragments per kilobase of transcript per million mapped reads; P < .0001). DKK1 expression can be regulated by activated Wnt signaling in vitro and correlates with activating canonical Wnt signaling mutations and low PSA mRNA in mCRPC biopsies (P < .05). DKK1 hypomethylation was associated with increased DKK1 mRNA expression (Pearson r = -0.66; P < .0001) in a rapid autopsy cohort (n = 7). DKK1-high mCRPC biopsies are infiltrated with significantly higher numbers of quiescent natural killer (NK) cells (P < .005) and lower numbers of activated NK cells (P < .0005). Growth inhibition of the human PCa model PC3 by the anti-DKK1 monoclonal antibody DKN-01 depends on the presence of NK cells in a severe combined immunodeficient xenograft mouse model.CONCLUSION: These results support DKK1 as a contributor to the immunosuppressive tumor microenvironment of DNPC. These data have provided the rationale for a clinical trial targeting DKK1 in mCRPC (ClinicalTrials.gov identifier: NCT03837353)., DKK1 has been implicated in causing erosive arthritis, the osteolytic phenotypes of multiple myeloma and metastatic breast cancer, and osteoblastic metastases of prostate cancer., Dickkopf-1 protein secretion was documented in breast, prostate and lung cancer lines, but was negligible in melanoma., LTS: Dickkopf-1 (DKK1) expression is increased in DNPC relative to prostate-specific antigen (PSA)-expressing mCRPC in the Stand Up to Cancer/Prostate Cancer Foundation discovery cohort (11.2 v 0.28 reads per kilobase per million mapped reads; q < 0.05; n = 117) and in the University of Washington/Fred Hutchinson Cancer Research Center cohort (9.2 v 0.99 fragments per kilobase of transcript per million mapped reads; P < .0001). DK, ckkopf-1 (DKK1) expression is increased in DNPC relative to prostate-specific antigen (PSA)-expressing mCRPC in the Stand Up to Cancer/Prostate Cancer Foundation discovery cohort (11.2 v 0.28 reads per kilobase per million mapped reads; q < 0.05; n = 117) and in the University of Washington/Fred Hutchinson Cancer Research Center cohort (9.2 v 0.99 fragments per kilobase of transcript per million mapped reads; P, The Wnt inhibitor Dickkopf-1 (DKK-1) has been associated with the occurrence of bone metastases in osteotropic prostate cancer by inhibiting osteoblastogenesis., These results reveal that p38 MAPK regulates DKK-1 in prostate cancer and may present a potential target in osteolytic prostate cancers., xenograft models. Epigenetic studies were carried out in a rapid autopsy cohort.RESULTS: Dickkopf-1 (DKK1) expression is increased in DNPC relative to prostate-specific antigen (PSA)-expressing mCRPC in the Stand Up to Cancer/Prostate Cancer Foundation discovery cohort (11.2 v 0.28 reads per kilobase per million mapped reads; q < 0.05; n = 117) and in the University of Washington/Fred Hutchinson Cancer Research Center cohort (9.2 v 0.99 fragments per kilobase of transcript per millio[SEP]Relations: mitogen-activated protein kinase binding has relations: molfunc_protein with DUSP1, molfunc_protein with DUSP1, molfunc_protein with DUSP9, molfunc_protein with DUSP9, molfunc_protein with PPM1D, molfunc_protein with PPM1D, molfunc_protein with PTPRJ, molfunc_protein with PTPRJ. benign neoplasm of prostate has relations: disease_disease with fibroma of prostate, disease_disease with fibroma of prostate. Definitions: prostate cancer defined as following: A primary or metastatic malignant tumor involving the prostate gland. The vast majority are carcinomas.. Dickkopf-1 defined as following: Dickkopf-related protein 1 (266 aa, ~29 kDa) is encoded by the human DKK1 gene. This protein is involved in both receptor binding and cell communication.. prostate-specific antigen defined as following: Prostate-specific antigen (261 aa, ~29 kDa) is encoded by the human KLK3 gene. This protein plays a role in both proteolysis and seminal fluid liquefaction.. p38 MAPK defined as following: A 38-kDa mitogen-activated protein kinase that is abundantly expressed in a broad variety of cell types. It is involved in the regulation of cellular stress responses as well as the control of proliferation and survival of many cell types. The kinase activity of the enzyme is inhibited by the pyridinyl-imidazole compound SB 203580.. breast defined as following: In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.. NK cells defined as following: Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.. AR defined as following: Aldose reductase (316 aa, ~36 kDa) is encoded by the human AKR1B1 gene. This protein plays a role in glucose metabolism.. DKK1 defined as following: This gene is involved in intercellular communication.. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.. xenograft defined as following: Tissues, cells or organs transplanted between animals of different species.. multiple myeloma defined as following: A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.. melanoma defined as following: A benign or malignant, primary or metastatic neoplasm affecting the melanocytes.. fragments defined as following: A physical quality in which the entity or structure is broken into pieces.. human defined as following: Members of the species Homo sapiens..", "label": "yes"} {"id": "converted_905", "sentence1": "Are viruses involved in the etiology of human subacute thyroiditis?", "sentence2": "he etiology of subacute (de Quervain's) thyroiditis (SAT) is uncertain, although it probably represents a nonspecific inflammatory response by the thyroid to a variety of viruses., Subacute thyroiditis is an inflammatory disorder of the thyroid caused probably by viruses. I, We believe that the etiologic agent was the Epstein-Barr virus because heterophile and Epstein-Barr virus-specific antibodies were positive., ltogether, these results indicate that the mechanism of inhibition of Spumavirinae infection by interferon differs from that described for the other Retroviridae, and particularly for types B, C and D viruses. Our data is of therapeutic interest since Spumavirinae have been linked to pathological processes such as de Quervain thyroiditis.[SEP]Relations: subacute thyroiditis has relations: disease_disease with thyroiditis (disease), disease_disease with thyroiditis (disease). regulation of excitatory postsynaptic membrane potential involved in skeletal muscle contraction has relations: bioprocess_bioprocess with modulation of excitatory postsynaptic potential, bioprocess_bioprocess with modulation of excitatory postsynaptic potential. Definitions: Quervain thyroiditis defined as following: Spontaneously remitting inflammatory condition of the THYROID GLAND, characterized by FEVER; MUSCLE WEAKNESS; SORE THROAT; severe thyroid PAIN; and an enlarged damaged gland containing GIANT CELLS. The disease frequently follows a viral infection.. viruses defined as following: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells.. human defined as following: Members of the species Homo sapiens..", "label": "yes"} {"id": "converted_1964", "sentence1": "Is there any involvement of the long non-coding RNA Gomafu in schizophrenia?", "sentence2": "The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing., Here, we profile these transcriptomic responses and show that long non-coding RNAs (lncRNAs) are dynamically regulated by neuronal activation, including acute downregulation of the lncRNA Gomafu, previously implicated in brain and retinal development. Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. These results functionally link activity-regulated lncRNAs and alternative splicing in neuronal function and suggest that their dysregulation may contribute to neurological disorders., Gomafu/MIAT/Rncr2 is a long noncoding RNA that has been proposed to control retinal cell specification, stem cell differentiation and alternative splicing of schizophrenia-related genes., The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing, Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. , Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. , The long non-coding RNA Gomafu is acutely regulated in response to neuronal activation and involved in schizophrenia-associated alternative splicing.[SEP]Relations: regulation of neural retina development has relations: bioprocess_protein with PTF1A, bioprocess_protein with PTF1A, bioprocess_protein with SIX3, bioprocess_protein with SIX3, bioprocess_protein with DLL4, bioprocess_protein with DLL4, bioprocess_bioprocess with negative regulation of neural retina development, bioprocess_bioprocess with negative regulation of neural retina development, bioprocess_bioprocess with positive regulation of neural retina development, bioprocess_bioprocess with positive regulation of neural retina development. Definitions: ERBB4 defined as following: Receptor tyrosine-protein kinase erbB-4 (1308 aa, ~147 kDa) is encoded by the human ERBB4 gene. This protein is involved in multicellular organismal development, cell proliferation and signal transduction.. SRSF1 defined as following: This gene is involved in both RNA processing and transport.. QKI defined as following: This gene is involved in both the biosynthesis and maintenance of mRNA.. serine/arginine-rich splicing factor 1 defined as following: Serine/arginine-rich splicing factor 2 (221 aa, ~25 kDa) is encoded by the human SRSF2 gene. This protein plays a role in the modulation of mRNA processing.. neurological disorders defined as following: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.. long noncoding RNA defined as following: A class of untranslated RNA molecules that are typically greater than 200 nucleotides in length and do not code for proteins. Members of this class have been found to play roles in transcriptional regulation, post-transcriptional processing, CHROMATIN REMODELING, and in the epigenetic control of chromatin.. schizophrenia defined as following: A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior..", "label": "yes"} {"id": "converted_4368", "sentence1": "Does TIMELESS-TIPIN participate in replisome disassembly?", "sentence2": "TIMELESS-TIPIN and UBXN-3 promote replisome disassembly during DNA replication termination in Caenorhabditis elegans., We show that UBXN-3 is important in vivo for replisome disassembly in the absence of TIMELESS-TIPIN. Correspondingly, co-depletion of UBXN-3 and TIMELESS causes profound synthetic lethality. Since the human orthologue of UBXN-3, FAF1, is a candidate tumour suppressor, these findings suggest that manipulation of CMG disassembly might be applicable to future strategies for treating human cancer.[SEP]Relations: TIMELESS has relations: protein_protein with TIPIN, protein_protein with TIPIN, bioprocess_protein with DNA repair, bioprocess_protein with DNA repair, bioprocess_protein with DNA replication, bioprocess_protein with DNA replication, bioprocess_protein with positive regulation of double-strand break repair via homologous recombination, bioprocess_protein with positive regulation of double-strand break repair via homologous recombination, bioprocess_protein with DNA replication checkpoint signaling, bioprocess_protein with DNA replication checkpoint signaling. Definitions: Caenorhabditis elegans defined as following: A species of nematode that is widely used in biological, biochemical, and genetic studies.. human defined as following: Members of the species Homo sapiens..", "label": "yes"} {"id": "converted_3930", "sentence1": "Has the olive tree pollen proteome been studied?", "sentence2": "Olive pollen is a major allergenic source worldwide due to its extensive cultivation. We have combined available genomics data with a comprehensive proteomics approach to get the annotated olive tree (Olea europaea L.) pollen proteome and define its complex allergenome. [SEP]", "label": "yes"} {"id": "converted_4489", "sentence1": "Is Mical an oxidoreductase?", "sentence2": "the MICALs, which are flavoprotein monooxygenase/hydroxylase enzymes that associate with flavin adenine dinucleotide (FAD) and use the co-enzyme nicotinamide adenine dinucleotide phosphate (NADPH) in Redox reactions, MICAL is an oxidoreductase, We have recently identified a new family of multidomain oxidoreductase (redox) enzymes, the MICALs,, the oxidoreductase MICAL[SEP]Relations: oxidoreductase complex has relations: cellcomp_protein with CBR4, cellcomp_protein with CBR4, cellcomp_protein with HSD17B8, cellcomp_protein with HSD17B8. Flavin adenine dinucleotide has relations: drug_protein with MAOB, drug_protein with MAOB, drug_protein with MAOA, drug_protein with MAOA, drug_protein with ACADM, drug_protein with ACADM. Definitions: oxidoreductase defined as following: This gene is involved in androgen catabolism.. FAD defined as following: A condensation product of riboflavin and adenosine diphosphate. The coenzyme of various aerobic dehydrogenases, e.g., D-amino acid oxidase and L-amino acid oxidase. (Lehninger, Principles of Biochemistry, 1982, p972).", "label": "yes"} {"id": "converted_3749", "sentence1": "Is the TFR1 gene dispensable for erythropoiesis?", "sentence2": "These studies describe how point mutations of the transferrin receptor can cause a microcytic anemia that does not respond to iron therapy and would not be detected by routine iron studies, such as serum ferritin., Ret-He was the only red cell marker affected prior to the onset of brain ID. The clinical practice of using anemia as the preferred biomarker for diagnosis of iron deficiency may need reconsidering., The restoration of EPO production and EPOR mRNA expression with ASP treatment activated EPOR downstream JAK2/STAT5 and PI3K/Akt signaling, induced their target genes, such as Bcl-xL, Fam132b and Tfrc, and increased Bcl-2/Bax ratio in bone marrow-derived mononuclear cells of CKD rats., Transferrin-bound iron binding to transferrin receptor 1 (TfR1) is essential for cellular iron delivery during erythropoiesis. , aken together, decreasing TfR1 expression during β-thalassemic erythropoiesis, either directly via induced haploinsufficiency or via exogenous apotransferrin, decreases ineffective erythropoiesis and provides an endogenous mechanism to upregulate hepcidin, leading to sustained iron-restricted erythropoiesis and preventing systemic iron overload in β-thalassemic mice., The type 1 transferrin receptor (TfR1) is well known as a key player in erythroid differentiation through its role in iron uptake. , The signaling functions of both TfR1 and TfR2 in erythroid cells were unexpected and these recent findings open a new field of research regarding the last steps of erythroid differentiation and their regulation., Erythropoiesis requires large amounts of iron for hemoglobin synthesis, which is mainly provided by macrophages and the intestines in a transferrin (Tf)-bound form., In humans, hematopoietic erythroid precursor cells express high levels of TFR1 and specifically take up the FTH homopolymer (H-ferritin)., We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the beta-thalassemia mouse models, compared with the control mice., Soluble transferrin receptor-1 (sTfR1) concentrations are increased in the plasma under two conditions that are associated with increased iron absorption, i.e. iron deficiency and increased erythropoiesis., Hemochromatosis is caused by mutations in HFE, a protein that competes with transferrin (TF) for binding to transferrin receptor 1 (TFR1)., Here we report that sorting nexin 3 (Snx3) facilitates the recycling of transferrin receptor (Tfrc) and thus is required for the proper delivery of iron to erythroid progenitors., These findings provide direct evidence that Tfr1 is essential for hematopoiesis through binding diferric transferrin to supply iron to cells.[SEP]Relations: hemochromatosis has relations: disease_protein with TFR2, disease_protein with TFR2. hemopoiesis has relations: bioprocess_protein with TWSG1, bioprocess_protein with TWSG1, bioprocess_protein with L3MBTL1, bioprocess_protein with L3MBTL1, bioprocess_protein with GFI1, bioprocess_protein with GFI1. Erythropoietin has relations: drug_protein with EPOR, drug_protein with EPOR. Definitions: iron defined as following: homeopathic drug. Tfr1 defined as following: Human TFRC wild-type allele is located in the vicinity of 3q29 and is approximately 33 kb in length. This allele, which encodes transferrin receptor protein 1, is involved in the regulation of cellular uptake of iron via receptor-mediated endocytosis.. transferrin receptor 1 defined as following: Homodimeric human Transferrin Receptors (M28B Peptidase Family) are type II membrane proteins involved in the cellular import of transferrin-bound iron and appear necessary for iron metabolism, cell function, and erythrocyte differentiation. (NCI). erythroid cells defined as following: The series of cells in the red blood cell lineage at various stages of differentiation.. erythroid defined as following: 1) Reddish in color. 2) relating to erythrocytes or their precursors.. EPOR defined as following: Erythropoietin receptor (508 aa, ~55 kDa) is encoded by the human EPOR gene. This protein is involved in signal transduction and erythroblast proliferation and differentiation.. EPO defined as following: Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.. transferrin defined as following: Serotransferrin (698 aa, ~77 kDa) is encoded by the human TF gene. This protein is involved in iron sequestration and transport.. transferrin receptor defined as following: This gene plays a role in iron metabolism.. TfR2 defined as following: Transferrin receptor protein 2 (801 aa, ~89 kDa) is encoded by the human TFR2 gene. This protein is involved in the mediation of cellular uptake of transferrin-iron complexes.. beta-thalassemia defined as following: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent.. hepcidin defined as following: Forms of hepcidin, a cationic amphipathic peptide synthesized in the liver as a prepropeptide which is first processed into prohepcidin and then into the biologically active hepcidin forms, including in human the 20-, 22-, and 25-amino acid residue peptide forms. Hepcidin acts as a homeostatic regulators of iron metabolism and also possesses antimicrobial activity.. microcytic anemia defined as following: Anemia in which the red blood cell volume is decreased.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. TF defined as following: A person who was assigned to the male gender at birth based on physical characteristics but who self-identifies psychologically and emotionally as female.. ASP defined as following: Fluid withdrawn from a body cavity, organ, cyst, or tumor.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. point mutations defined as following: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.. rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. intestines defined as following: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.. CKD defined as following: Impairment of the renal function secondary to chronic kidney damage persisting for three or more months.. Bcl-xL defined as following: This gene is an apoptotic regulator that can have anti or pro apoptotic effects.. hematopoiesis defined as following: The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY).. NGAL defined as following: Human LCN2 wild-type allele is located in the vicinity of 9q34 and is approximately 5 kb in length. This allele, which encodes neutrophil gelatinase-associated lipocalin protein, may be involved in both the modulation of inflammation and the regulation of the transport of hydrophobic substances (ie. retinol, lipopolysaccharide). The expression of this gene may be elevated in many cancers and inflammatory diseases.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. bone marrow-derived mononuclear cells defined as following: A biological sample containing mononuclear cells isolated from the bone marrow of an experimental subject.. humans defined as following: Members of the species Homo sapiens.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary..", "label": "no"} {"id": "converted_1962", "sentence1": "Do normal cells express the protein TERT?", "sentence2": "Since telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells, it has become a very promising target for anti-cancer therapy, Telomerase plays a pivotal role in cellular immortality and tumorigenesis. Its activity is normally not detectable in most somatic cells while it is reactivated in the vast majority of cancer cells. Therefore, inhibition of telomerase has been viewed as a promising anticancer approach due to its specificity for cancer cells., Telomerase activity is found in 85%-90% of all human cancers but not in their adjacent normal cells. Human telomerase reverse transcriptase (hTERT) is an essential component in the telomerase complex that plays an important role in telomerase activity., elomerase activation is considered to be a critical step in carcinogenesis and its activity correlates closely with human telomerase reverse transcriptase (hTERT) expression. Since only tumor cells that express telomerase activity would activate this promoter, the hTERT proximal promoter allows for preferential expression of viral genes in tumor cells, leading to selective viral replication[SEP]Relations: Protein S human has relations: drug_drug with Platelet Activating Factor, drug_drug with Platelet Activating Factor, drug_protein with PROC, drug_protein with PROC, drug_drug with Iloprost, drug_drug with Iloprost, drug_drug with Dienogest, drug_drug with Dienogest, drug_drug with Sarpogrelate, drug_drug with Sarpogrelate. Definitions: human telomerase reverse transcriptase defined as following: Telomerase reverse transcriptase (1132 aa, ~127 kDa) is encoded by the human TERT gene. This protein plays a role in both the replication and maintenance of telomeres.. telomerase defined as following: An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.. cancer cells defined as following: Cells of, or derived from, a malignant tumor.. human defined as following: Members of the species Homo sapiens.. hTERT defined as following: Human TERT wild-type allele is located in the vicinity of 5p15.33 and is approximately 42 kb in length. This allele, which encodes telomerase reverse transcriptase protein, is involved in the replication of telomeres. Aberrant expression of the allele at elevated levels may contribute to oncogenesis.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. somatic cells defined as following: Nucleated cell which has one or more diploid sets (46 pairs) of chromosomes.. tumor cells defined as following: Cells of, or derived from, a tumor.. promoter defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. viral genes defined as following: The functional hereditary units of VIRUSES..", "label": "no"} {"id": "converted_649", "sentence1": "Is low T3 syndrome related with high BNP in cardiac patients?", "sentence2": "BNP and fT3 are independently associated with exercise capacity in severely compromised HF patients., fter adjustment for known confounders, NT-pro-BNP was significantly associated with fT3 and low-T3 syndrome. fT3 (HR 0.58, 95%CI 0.34-0.98) and low-T3 syndrome (HR 3.0, 95%CI 1.4-6.3) were predictive for mortality after adjustment for NT-pro-BNP levels and other cardiovascular prognostic variables., fT3 and low-T3 syndrome are significantly related to NT-pro-BNP in patients with cardiovascular disease, but are predictors of mortality independently of NT-pro-BNP and other known cardiovascular risk parameters., Higher NT-pro BNP concentrations were related to lower total T3 concentrations (r = -0.294, p = 0.011) and to higher reverse T3 concentrations (r = 0.353, p = 0.002)[SEP]Relations: cardiovascular disease has relations: contraindication with Dipotassium phosphate, contraindication with Dipotassium phosphate, contraindication with Polyethylene glycol 300, contraindication with Polyethylene glycol 300, contraindication with Zinc sulfate, contraindication with Zinc sulfate, contraindication with Succinylcholine, contraindication with Succinylcholine. hydrops fetalis has relations: disease_protein with FOXP3, disease_protein with FOXP3. Definitions: cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. fT3 defined as following: A traditional unit of volume equal to 1728 cubic inches, or 1/27 cubic yard, or 0.028 316 85 cubic meter (28.316 85 liters). The cubic foot holds about 7.4805 US gallons.. NT-pro-BNP defined as following: N-terminal fragment brain natriuretic protein (76 aa, ~9 kDa) is encoded by the human NPPB gene. This protein is a marker for cardiac failure.. cardiovascular defined as following: The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body.. HF defined as following: Abnormal accumulation of serous fluid in two or more fetal compartments, such as SKIN; PLEURA; PERICARDIUM; PLACENTA; PERITONEUM; AMNIOTIC FLUID. General fetal EDEMA may be of non-immunologic origin, or of immunologic origin as in the case of ERYTHROBLASTOSIS FETALIS.. BNP defined as following: A recombinant version of the cardiac neurohormone, human B-type natriuretic peptide (hBNP) produced by the ventricular myocardium. Nesiritide binds to natriuretic peptide receptors on vascular smooth muscle and endothelial cells, through which it triggers guanylate cyclase dependent signal transduction resulting in increase of intracellular concentrations of cGMP. This leads to smooth muscle cell relaxation causing arterial and venous dilatation..", "label": "yes"} {"id": "converted_2666", "sentence1": "Is sternotomy closure done using either a sternal ZipFix™ implant or conventional steel wire following cardiac surgery?", "sentence2": "o determine the difference in sternal infection and other infectious events between conventional wire and cable-tie-based closure techniques post-sternotomy in a collective of patients after cardiac surgery., Our study underlines a neutral effect of the sternal ZipFix™ system in patients regarding sternal infection. Postoperative complications are similar in both sternal closure methods. The cable-tie-based system is fast, easy to use, reliable and safe., Wire closure still remains the preferred technique despite reasonable disadvantages. Associated complications, such as infection and sternal instability, cause time- and cost-consuming therapies. We present a new tool for sternal closure with its first clinical experience and results.METHODS: The sternal ZipFix(TM) System is based on the cable-tie principle. , In our initial evaluation, the short-term results have shown that the sternal ZipFix(TM) can be used safely and effectively. It is fast, easy to use and serves as a potential alternative for traditional wire closure., To determine the difference in sternal infection and other infectious events between conventional wire and cable-tie-based closure techniques post-sternotomy in a collective of patients after cardiac surgery.[SEP]Relations: sternum has relations: anatomy_anatomy with endochondral element, anatomy_anatomy with endochondral element. Definitions: infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. sternal defined as following: A long, narrow, and flat bone commonly known as BREASTBONE occurring in the midsection of the anterior thoracic segment or chest region, which stabilizes the rib cage and serves as the point of origin for several muscles that move the arms, head, and neck..", "label": "yes"} {"id": "converted_3183", "sentence1": "Are protamines ubiquitously expressed?", "sentence2": "Protamines are nuclear proteins which are specifically expressed in haploid male germ cells.[SEP]Relations: Protamine has relations: drug_effect with Inflammatory abnormality of the skin, drug_effect with Inflammatory abnormality of the skin, drug_effect with Fever, drug_effect with Fever, drug_effect with Agitation, drug_effect with Agitation, drug_effect with Pain, drug_effect with Pain, drug_effect with Increased hemoglobin, drug_effect with Increased hemoglobin. Definitions: Protamines defined as following: A group of simple proteins that yield basic amino acids on hydrolysis and that occur combined with nucleic acid in the sperm of fish. Protamines contain very few kinds of amino acids. Protamine sulfate combines with heparin to form a stable inactive complex; it is used to neutralize the anticoagulant action of heparin in the treatment of heparin overdose. (From Merck Index, 11th ed; Martindale, The Extra Pharmacopoeia, 30th ed, p692). nuclear proteins defined as following: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.. germ cells defined as following: The reproductive cells in multicellular organisms at various stages during GAMETOGENESIS.. protamines defined as following: A group of simple proteins that yield basic amino acids on hydrolysis and that occur combined with nucleic acid in the sperm of fish. Protamines contain very few kinds of amino acids. Protamine sulfate combines with heparin to form a stable inactive complex; it is used to neutralize the anticoagulant action of heparin in the treatment of heparin overdose. (From Merck Index, 11th ed; Martindale, The Extra Pharmacopoeia, 30th ed, p692).", "label": "no"} {"id": "converted_1751", "sentence1": "Is Thalidomide currently a marketed drug?", "sentence2": "In this retrospective study, pharmacy claims were analyzed for those patients with a diagnosis of MM who received thalidomide,, The Japanese POEMS syndrome with Thalidomide (J-POST) Trial is a phase II/III multicentre, double-blinded, randomised, controlled trial that aims to evaluate the efficacy and safety of a 24-week treatment with thalidomide in POEMS syndrome,, Thalidomide could relieve clinical symptoms and intestinal mucosal lesions effectively in children with refractory inflammatory bowel disease (IBD) from the pre-clinical study., Thalidomide is now available as an investigational drug in the USA., The STEPStrade mark (System for Thalidomide Education and Prescribing Safety) Program has been developed by Celgene, the commercial manufacturer of thalidomide, to ensure compliance with prescription and usage protocols., New uses of thalidomide., Thalidomide is an anti-angiogenesis agent that currently is being evaluated in the treatment of various types of cancer., The comeback of thalidomide to the legitimate status of a marketed drug came in 1998 when it received FDA approval for the treatment of erythema nodosum leprosum (ENL), Thalidomide is considered the drug of choice for the treatment of ENL, but for other conditions, it is recommended only when resistance to the currently available form of therapy is encountered, Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy, Thalidomide, once banned, has returned to the center of controversy with the Food and Drug Administration's (FDA's) announcement that thalidomide will be placed on the market for the treatment of erythema nodosum leprosum, a severe dermatological complication of Hansen's disease. , In 1998, FDA approved the marketing of thalidomide (Thalomid, Celgene). , In 1998 the US Food and Drug Administration approved thalidomide exclusively for the treatment of ENL, and strict conditions were stipulated for its use in order to prevent teratogenic adverse effects., BACKGROUND: The use of thalidomide during the 1950s resulted in teratogenic effects in thousands of infants. Although thalidomide is currently approved for the treatment of a complication of leprosy, it is commercially available to treat other diseases through a controlled distribution system., The comeback of thalidomide to the legitimate status of a marketed drug came in 1998 when it received FDA approval for the treatment of erythema nodosum leprosum (ENL).[SEP]Relations: Thalidomide has relations: drug_drug with Cocaine, drug_drug with Cocaine, drug_drug with Etomidate, drug_drug with Etomidate, drug_drug with Diamorphine, drug_drug with Diamorphine, drug_drug with Harmaline, drug_drug with Harmaline, drug_drug with Propanidid, drug_drug with Propanidid. Definitions: drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. cancer defined as following: A malignant tumor at the original site of growth.. thalidomide defined as following: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.. leprosy defined as following:leprosy vaccine
. MM defined as following: A unit of concentration (molarity unit) equal to one thousandth of a mole (10E-3 mole) of solute per one liter of solution.. anti-angiogenic drug defined as following: Agents and endogenous substances that antagonize or inhibit the development of new blood vessels.. ENL defined as following: Human MLLT1 wild-type allele is located in the vicinity of 19p13.3 and is approximately 70 kb in length. This allele, which encodes protein ENL, plays a role in the activation of transcription by RNA polymerase II. Mixed-lineage leukemias are associated with the translocation t(11;19)(q23;p13.3) of the gene with the MLL gene.. lepromatous leprosy defined as following: A chronic communicable infection which is a principal or polar form of LEPROSY. This disorder is caused by MYCOBACTERIUM LEPRAE and produces diffuse granulomatous skin lesions in the form of nodules, macules, or papules. The peripheral nerves are involved symmetrically and neural sequelae occur in the advanced stage.. IBD defined as following: Gastrointestinal symptoms characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause.. POEMS syndrome defined as following: A multisystemic disorder characterized by a sensorimotor polyneuropathy (POLYNEUROPATHIES), organomegaly, endocrinopathy, monoclonal gammopathy, and pigmentary skin changes. Other clinical features which may be present include EDEMA; CACHEXIA; microangiopathic glomerulopathy; pulmonary hypertension (HYPERTENSION, PULMONARY); cutaneous necrosis; THROMBOCYTOSIS; and POLYCYTHEMIA. This disorder is frequently associated with osteosclerotic myeloma. (From Adams et al., Principles of Neurology, 6th ed, p1335; Rev Med Interne 1997;18(7):553-62). Thalidomide defined as following: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action..", "label": "yes"} {"id": "converted_1238", "sentence1": "Is the Snord116 cluster associated with the Prader-Willi syndrome?", "sentence2": "All three deletions included SNORD116, but only two encompassed parts of SNURF-SNRPN, implicating SNORD116 as the major contributor to the Prader-Willi phenotype. Our case adds further information about genotype-phenotype correlation and supports the hypothesis that SNORD116 plays a major role in the pathogenesis of Prader-Willi syndrome, These results demonstrate that the AS candidate drug topotecan acts predominantly through stabilizing R loops and chromatin decondensation at the paternally expressed PWS Snord116 locus. Our study holds promise for targeted therapies to the Snord116 locus for both AS and PWS., Prader-Willi syndrome (PWS) is caused by the loss of RNA expression from an imprinted region on chromosome 15 that includes SNRPN, SNORD115, and SNORD116. , Recently published data strongly suggest a role for the paternally expressed small nucleolar RNA (snoRNA) cluster, SNORD116, in PWS etiology., Whereas loss of function of the SNORD116 genes appears to be responsible for the major features of PWS, the role of the other genes is less clear. , Recent data suggest that snoRNA Snord116 is important for the pathogenesis of Prader-Willi syndrome (PWS) characterized by hyperphagia and obesity. The current study was conducted to assess a potential cellular link between Snord116 and phenotypes of PWS. , The imprinted Snurf-Snrpn chromosomal domain contains two large arrays of tandemly repeated, paternally expressed box C/D small-nucleolar RNA (snoRNA) genes: the SNORD115 (H/MBII-52) and SNORD116 (H/MBII-85) gene clusters believed to play key roles in the fine-tuning of serotonin receptor (5-HT2C) pre-mRNA processing and in the etiology of the Prader-Willi Syndrome (PWS), respectively, There are multiple imprinted genes in this region, the loss of which contribute to the complete phenotype of Prader-Willi syndrome. However, absence of a small nucleolar organizing RNA gene, SNORD116, seems to reproduce many of the clinical features., Both kits should be made available for accurate characterization of PWS/AS deletion subtypes as well as evaluating for IC and SNORD116 microdeletions., There are multiple imprinted genes in this region, the loss of which contribute to the complete phenotype of Prader-Willi syndrome. However, absence of a small nucleolar organizing RNA gene, SNORD116, seems to reproduce many of the clinical features. , Although the SNORD116 gene cluster has become a prime candidate for PWS, it cannot be excluded that other paternally expressed genes in the chromosomal region 15q11q13 contribute to the full phenotype., In addition, recently published data provide strong evidence in support of a role for the snoRNA SNORD116 cluster (HBII-85) in PWS etiology., Identification and characterization of this case provide unequivocal evidence for a critical role for the SNORD116 snoRNA molecules in PWS pathogenesis. [SEP]Relations: Prader-Willi syndrome has relations: disease_protein with SNORD116-1, disease_protein with SNORD116-1, disease_protein with SNORD115-1, disease_protein with SNORD115-1, disease_protein with SNRPN, disease_protein with SNRPN, disease_protein with LZTR1, disease_protein with LZTR1, disease_protein with NF1, disease_protein with NF1. Definitions: locus defined as following: The position of a gene or a chromosomal marker on a chromosome; also, a stretch of DNA at a particular place on a particular chromosome. The use of locus is sometimes restricted to mean regions of DNA that are expressed.. SNURF-SNRPN defined as following: This gene plays a role in splicing of mRNA.. cellular defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. PWS defined as following: A technique that uses focused waves of broadband, low-spatially-coherent light to illuminate a sample, and forms an image by acquiring far field back-scattered photons. A partial spectrum of the back-scattered light intensity is recorded and analyzed.. hyperphagia defined as following: Ingestion of a greater than optimal quantity of food.. chromosomal region defined as following: Any subdivision of a chromosome along its length. [GOC:dos]. Prader-Willi Syndrome defined as following: An autosomal dominant disorder caused by deletion of the proximal long arm of the paternal chromosome 15 (15q11-q13) or by inheritance of both of the pair of chromosomes 15 from the mother (UNIPARENTAL DISOMY) which are imprinted (GENETIC IMPRINTING) and hence silenced. Clinical manifestations include MENTAL RETARDATION; MUSCULAR HYPOTONIA; HYPERPHAGIA; OBESITY; short stature; HYPOGONADISM; STRABISMUS; and HYPERSOMNOLENCE. (Menkes, Textbook of Child Neurology, 5th ed, p229). deletions defined as following: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. Prader-Willi syndrome defined as following: An autosomal dominant disorder caused by deletion of the proximal long arm of the paternal chromosome 15 (15q11-q13) or by inheritance of both of the pair of chromosomes 15 from the mother (UNIPARENTAL DISOMY) which are imprinted (GENETIC IMPRINTING) and hence silenced. Clinical manifestations include MENTAL RETARDATION; MUSCULAR HYPOTONIA; HYPERPHAGIA; OBESITY; short stature; HYPOGONADISM; STRABISMUS; and HYPERSOMNOLENCE. (Menkes, Textbook of Child Neurology, 5th ed, p229).", "label": "yes"} {"id": "converted_3193", "sentence1": "Is the Philadelphia chromosome a fusion between parts of chromosomes 1 and 9?", "sentence2": " The Philadelphia chromosome, t(9;22)(q34;q11), is present in 95% of CML patients, resulting in constitutive tyrosine kinase activity; however, ~5% of CML patients possess a Philadelphia variant. , Chronic Myeloid Leukemia (CML) is myeloproliferative neoplasm characterized by Philadelphia chromosome which is a balanced translocation between chromosome 9 and 22 in 90% of cases., Chronic myeloid leukemia is a stem cell disease with the presence of Philadelphia chromosome generated through reciprocal translocation of chromosome 9 and 22. [SEP]Relations: Philadelphia-positive myelogenous leukemia has relations: disease_disease with myeloid leukemia, disease_disease with myeloid leukemia. atypical chronic myeloid leukemia has relations: disease_protein with SETBP1, disease_protein with SETBP1, disease_protein with ETNK1, disease_protein with ETNK1, disease_protein with CSF3R, disease_protein with CSF3R. Myeloproliferative disorder has relations: disease_phenotype_positive with chronic myelogenous leukemia, BCR-ABL1 positive, disease_phenotype_positive with chronic myelogenous leukemia, BCR-ABL1 positive. Definitions: Chronic myeloid leukemia defined as following: Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.. CML defined as following: chronic leukemia in which myeloid progenitor cells predominate; the hallmark of CML, the Philadelphia chromosome, is a reciprocal translocation between chromosomes 9 and 22 which activates the proto- oncogene c-abl.. chromosome 9 defined as following: A specific pair of GROUP C CHROMSOMES of the human chromosome classification.. myeloproliferative neoplasm defined as following: A clonal hematopoietic stem cell disorder, characterized by proliferation in the bone marrow of one or more of the myeloid (i.e., granulocytic, erythroid, megakaryocytic, and mast cell) lineages. It is primarily a neoplasm of adults. (WHO 2008). Philadelphia chromosome defined as following: An aberrant form of human CHROMOSOME 22 characterized by translocation of the distal end of chromosome 9 from 9q34, to the long arm of chromosome 22 at 22q11. It is present in the bone marrow cells of 80 to 90 per cent of patients with chronic myelocytic leukemia (LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE).. chromosomes 1 defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.. Philadelphia defined as following: City located in Pennsylvania..", "label": "no"} {"id": "converted_4400", "sentence1": "Does the royal jelly contain proteins?", "sentence2": " We observed differences in the metabolome, proteome, and phytosterol compositions of royal jelly synthesized by nurse bees from multi-pesticide exposed colonies, including significant reductions of key nutrients such as 24-methylenecholesterol, major royal jelly proteins, and 10-hydroxy-2-decenoic acid. , Two-dimensional electrophoresis was used for the fractionation of royal jelly proteins, the main bioactive compounds of RJ, such as proteins, peptides, fatty acids, and phenolic, the expression of four of the major royal jelly proteins (MRJP1, MRJP2, MRJP4, and MRJP5) and also several proteins associated with carbohydrate metabolism and energy synthesis, the antioxidant system, detoxification, biosynthesis, amino acid metabolism, transcription and translation, protein folding and binding, olfaction, and learning and memory.[SEP]Relations: 12-Hydroxydodecanoic Acid has relations: drug_protein with ADH5, drug_protein with ADH5. Definitions: fatty acids defined as following: Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed). proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. phytosterol defined as following: A class of organic compounds known as sterols or STEROIDS derived from plants.. nutrients defined as following: Various components of food that are required for nourishment..", "label": "yes"} {"id": "converted_428", "sentence1": "Have gnotobiotic animal models been used for the study of bowel disease?", "sentence2": "Host gene expression in the colon of gnotobiotic interleukin-2-deficient mice colonized with commensal colitogenic or noncolitogenic bacterial strains: common patterns and bacteria strain specific signatures., Specific pathogen-free (SPF), but not germfree (GF), interleukin (IL)-2-deficient (IL-2-/-) mice develop inflammatory bowel disease (IBD) at 10 to 15 weeks of age. Gnotobiotic IL-2-/- mice monocolonized with E. coli mpk develop IBD at 25 to 33 weeks of age but not B. vulgatus mpk, E. coli Nissle 1917, or mice cocolonized with both E. coli mpk and B. vulgatus, Lactobacillus reuteri promotes Helicobacter hepaticus-associated typhlocolitis in gnotobiotic B6.129P2-IL-10(tm1Cgn) (IL-10(-/-) ) mice., To model inflammatory bowel disease, we assessed infection with Helicobacter hepaticus 3B1 (ATCC 51449) and a potential probiotic Lactobacillus reuteri (ATCC PTA-6475) in gnotobiotic B6.129P2-IL-10(tm1Cgn) (IL-10(-/-) ) mice. No typhlocolitis developed in germ-free controls (n=21) or in L. reuteri (n=8) or H. hepaticus (n=18) mono-associated mice for 20 weeks post-infection. As positive controls, three specific pathogen-free IL-10(-/-) mice dosed with H. hepaticus developed severe typhlocolitis within 11 weeks. , These data support that the development of typhlocolitis in H. hepaticus-infected IL-10(-/-) mice required co-colonization with other microbiota and in this study, required only L. reuteri. , When transferred to gnotobiotic mice, gut microbiomes from mice with active disease versus treatment-induced remission elicited varying degrees of colitis. , The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases., The immunomodulatory effects of microbiota and probiotics for inflammatory bowel diseases and the role of bacteria in their etiologies are being studied in gnotobiotic systems., To model inflammatory bowel disease, we assessed infection with Helicobacter hepaticus 3B1 (ATCC 51449) and a potential probiotic Lactobacillus reuteri (ATCC PTA-6475) in gnotobiotic B6.129P2-IL-10(tm1Cgn) (IL-10(-/-) ) mice., Gnotobiotic piglets may be used as a suitable animal model to study colitis induced by C. jejuni, The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases, We investigated the changes in renal expression of Kl as a consequence of colitis. METHODS: We studied 3 mouse models of IBD: colitis induced by trinitrobenzene sulfonic acid, colitis induced by microflora (in gnotobiotic interleukin-10(-/-)), and colitis induced by adoptive transfer of CD4(+)CD45RB(high) T cells. , METHODS: We studied 3 mouse models of IBD: colitis induced by trinitrobenzene sulfonic acid, colitis induced by microflora (in gnotobiotic interleukin-10(-/-)), and colitis induced by adoptive transfer of CD4(+)CD45RB(high) T cells. [SEP]Relations: inflammatory bowel disease has relations: disease_phenotype_positive with Abnormal intestine morphology, disease_phenotype_positive with Abnormal intestine morphology, disease_phenotype_positive with Abnormal intestine morphology, disease_phenotype_positive with Abnormal intestine morphology, contraindication with Phenobarbital, contraindication with Phenobarbital, contraindication with Phenobarbital, contraindication with Phenobarbital, disease_protein with GHRL, disease_protein with GHRL. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. Kl defined as following: Human KITLG wild-type allele is located in the vicinity of 12q22 and is approximately 88 kb in length. This allele, which encodes Kit ligand protein, plays a role in germ cell and neural cell development and in hematopoiesis.. infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. inflammatory bowel diseases defined as following: Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS.. Lactobacillus reuteri defined as following: A species of gram-positive, rod-shaped LACTIC ACID bacteria found naturally in the human intestinal flora and BREAST MILK.. human defined as following: Members of the species Homo sapiens.. autoimmune diseases defined as following: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.. IBD defined as following: Gastrointestinal symptoms characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause.. bacteria defined as following: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.. colitis defined as following: Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER.. bowel disease defined as following: Pathological processes in any segment of the INTESTINE from DUODENUM to RECTUM..", "label": "yes"} {"id": "converted_1182", "sentence1": "Is macroautophagy a selective degradation process?", "sentence2": "Selective autophagy, Macroautophagy (autophagy) is a bulk degradation system for cytoplasmic components and is ubiquitously found in eukaryotic cells, Here we show that selective autophagy downregulates Ty1 transposition, We propose that selective autophagy safeguards genome integrity against excessive insertional mutagenesis caused during nutrient starvation by transposable elements in eukaryotic cells., Moreover, it is becoming apparent that proteins, organelles, and pathogens can be targeted for autophagic clearance by selective mechanisms, Cell spreading required ref(2)P, the Drosophila p62 multiadaptor, implicating selective autophagy as a novel mechanism for modulating cortical dynamics, The selective macroautophagic degradation, There is growing evidence that macroautophagic cargo is not limited to bulk cytosol in response to starvation and can occur selectively for substrates, including aggregated proteins., It remains unclear, however, whether starvation-induced and selective macroautophagy share identical adaptor molecules to capture their cargo. Here, we report that Alfy, a phosphatidylinositol 3-phosphate-binding protein, is central to the selective elimination of aggregated proteins., We propose that Alfy plays a key role in selective macroautophagy by bridging cargo to the molecular machinery that builds autophagosomes., Thus, cytoplasmic NBR1 might be important to maintain basal levels of selective macroautophagy in these neurons., we could show that Smatg8 and Smatg4 are not only required for nonselective macroautophagy, but for selective macropexophagy as well., The latter is performed by proteasome-mediated degradation, chaperone-mediated autophagy (CMA), and selective macroautophagy,, Here we demonstrate a role for PtdIns 4-kinases and PtdIns4P 5-kinases in selective and nonselective types of autophagy in yeast., Macroautophagy (hereafter autophagy) is a degradative cellular pathway that protects eukaryotic cells from stress, starvation, and microbial infection., Previously, we showed that macroautophagy is necessary for conidiation in the rice-blast fungus Magnaporthe oryzae. Here, we analyzed the physiological function(s) of selective autophagy in Magnaporthe, Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins., Selective macroautophagy (autophagy) of ubiquitinated protein is implicated as a compensatory mechanism of the ubiquitin-proteasome system. p62/SQSTM1 is a key molecule managing autophagic clearance of polyubiquitinated proteins., Whole organelle turnover is mediated through macroautophagy, a process by which autophagosomes deliver mitochondria to the lysosome for hydrolytic degradation. While mitochondrial autophagy can occur as part of a nonselective upregulation of autophagy, selective degradation of damaged or unneeded mitochondria (mitophagy) is a rapidly growing area in development, cancer, and neurodegeneration, particularly with regard to Parkinson's disease, BAG3 was recently described as a mediator of a novel macroautophagy pathway that uses the specificity of heat shock protein 70 (HSP70) to misfolded proteins and also involves other protein partners, such as HSPB8., two Parkinson disease (PD) associated genes, PINK1 and Parkin, were shown to mediate the degradation of damaged mitochondria via selective autophagy (mitophagy), Here we show that whole mitochondria are turned over via macroautophagy., Does Huntingtin play a role in selective macroautophagy?, In the discussion here I suggest that Htt may have a normal function in the lysosomal mechanism of selective macroautophagy involved in its own degradation, Macroautophagy induced by ethanol seemed to be selective for damaged mitochondria and accumulated lipid droplets, but not long-lived proteins, which could account for its protective effects, Although macroautophagy can be nonspecific, there are many examples of selective sequestration including pexophagy, mitophagy and the cytoplasm to vacuole targeting (Cvt) pathway., Mitochondria autophagy (mitophagy) is the process of selective degradation of mitochondria that has an important role in mitochondrial quality control., One of the genes identified, YLR356W, is required for mitophagy, but not for macroautophagy or other types of selective autophagy., A genomic screen for yeast mutants defective in selective mitochondria autophagy., Mitophagy is the process of selective mitochondrial degradation via autophagy, which has an important role in mitochondrial quality control., Analysis of this set of targeted deletion mutants demonstrated that loss of any of the 16 genes necessary for nonselective macroautophagy renders the fungus unable to cause rice blast disease, due to impairment of both conidial programmed cell death and appressorium maturation. In contrast, genes necessary only for selective forms of autophagy, such as pexophagy and mitophagy, are dispensable for appressorium-mediated plant infection., This gene is not required for other types of selective autophagy or for nonspecific macroautophagy., However, in contrast to the core autophagy genes such as atg5 and atg7, expression of ulk1 is not essential for induction of macroautophagy in response to nutrient deprivation or for survival of newborn mice. Together, these data suggest that the ATG1 homologue, Ulk1, is a component of the selective autophagy machinery that leads to the elimination of organelles in erythroid cells rather that an essential mechanistic component of autophagy., Growing evidence supports an active role for dysregulated macroautophagy (autophagic stress) in neuronal cell death and neurodegeneration. Alterations in mitochondrial function and dynamics are also strongly implicated in neurodegenerative diseases. Interestingly, whereas the core autophagy machinery is evolutionarily conserved and shared among constitutive and induced or selective autophagy, recent studies implicate distinct mechanisms regulating mitochondrial autophagy (mitophagy) in response to general autophagic stimuli., We discovered that activation of the UPR in yeast also induces a new branch of macroautophagy that selectively targets the ER. We term this process \"ER-phagy\", in analogy to pexophagy and mitophagy, the two other known forms of organelle-specific marcoautophagy. ER-phagy involves the generation of autophagosomes that selectively include ER membranes and whose delimiting double membranes also derive, at least in part, from the ER., This suggests that in fungi an organism-specific form of selective autophagy may occur, for which specialized Atg proteins have evolved., ransfer of Y. lipolytica cells from oleate/ethylamine to glucose/ammonium chloride medium leads to selective macroautophagy of peroxisomes., Insulin-dependent signaling regulates azurophil granule-selective macroautophagy in human myeloblastic cells., We show that insulin-dependent signals regulate azurophil granule-selective macroautophagy in human myeloid cells., By contrast, other organelles, including the mitochondria, endoplasmic reticulum, and Golgi apparatus remained intact, indicating that the macroautophagy selectively targeted azurophil granules., Thus, insulin-dependent signals are responsible for the control of azurophil granule-selective macroautophagy via Akt-dependent pathways, Eukaryotic cells have the ability to degrade proteins and organelles by selective and nonselective modes of micro- and macroautophagy., For example, pexophagy is a selective process for the regulated degradation of peroxisomes by autophagy., We have characterized biochemically, morphologically, and genetically two distinct pathways for the selective degradation of peroxisomes in Pichia pastoris. These pathways are independently regulated and analogous to microautophagy and macroautophagy that have been defined in mammalian cells., If we are willing to slightly modify our definition of autophagy, with a focus on \"degradation of a cell's own components through the lysosomal/vacuolar machinery,\" we can include a newly documented process, programmed nuclear destruction (PND)., Autophagy is a lysosomal degradation pathway that can sequester cytosolic material, including organelles, nonspecifically in a process called nonselective macroautophagy, or target specific protein aggregates designated for destruction in a process called selective autophagy., Selective macroautophagy uses double-membrane vesicles, termed autophagosomes, to transport cytoplasmic pathogens, organelles and protein complexes to the vacuole for degradation., Autophagy (macroautophagy), a highly conserved eukaryotic mechanism, is a non-selective degradation process, helping to maintain a balance between the synthesis, degradation and subsequent recycling of macromolecules to overcome various stress conditions., Whole organelle turnover is mediated through macroautophagy, a process by which autophagosomes deliver mitochondria to the lysosome for hydrolytic degradation., Macroautophagy is a catabolic process by which the cell degrades cytoplasmic components through the lysosomal machinery., Macroautophagy maintains cellular homeostasis through targeting cytoplasmic contents and organelles into autophagosomes for degradation., Macroautophagy is a catabolic process by which cytosolic components are sequestered by double membrane vesicles called autophagosomes and sorted to the lysosomes/vacuoles to be degraded., Macroautophagy (hereafter autophagy) is a cellular degradation process, which in yeast is induced in response to nutrient deprivation., Macroautophagy was thought to be an unspecific bulk degradation process., Autophagy is a highly regulated intracellular degradation process by which cells remove cytosolic long-lived proteins and damaged organelles, and can be monitored by imaging the incorporation of microtubule-associated light chain 3 (LC3) fused to a fluorescent protein (GFP or mCherry) into nascent autophagosomes., Beside macroautophagy, there are several forms of selective autophagy, including chaperone-mediated autophagy (CMA), cytoplasm to vacuole targeting (Cvt), pexophagy and mitophagy., Macroautophagy (commonly referred to as autophagy) is the process by which intact organelles and/or large portions of the cytoplasm are engulfed within double-membraned autophagic vacuoles for degradation., This analysis demonstrated that Atg proteins required for non-selective macroautophagy are conserved from yeast to man, stressing the importance of this process in cell survival and viability., Part of the degradation of intracellular proteins occurs in the lysosomes and is mediated by macroautophagy.[SEP]Relations: macroautophagy has relations: bioprocess_bioprocess with selective autophagy, bioprocess_bioprocess with selective autophagy, bioprocess_bioprocess with selective autophagy, bioprocess_bioprocess with selective autophagy, bioprocess_bioprocess with autophagy, bioprocess_bioprocess with autophagy, bioprocess_bioprocess with autophagy, bioprocess_bioprocess with autophagy, bioprocess_protein with STAM, bioprocess_protein with STAM. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. genome defined as following: Anatomical set of genes in all the chromosomes.. ulk1 defined as following: Serine/threonine-protein kinase ULK1 (1050 aa, ~113 kDa) is encoded by the human ULK1 gene. This protein is involved in protein phosphorylation that mediates the autophagocytotic process.. organelle defined as following: Cell part which consists of macromolecules aggregated into discrete structures in the protoplasm. (Digital Anatomist Foundational Model). yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. GFP defined as following: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.. mitochondria defined as following: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed). peroxisomes defined as following: Microbodies which occur in animal and plant cells and in certain fungi and protozoa. They contain peroxidase, catalase, and allied enzymes. (From Singleton and Sainsbury, Dictionary of Microbiology and Molecular Biology, 2nd ed). transposable elements defined as following: Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.. erythroid cells defined as following: The series of cells in the red blood cell lineage at various stages of differentiation.. atg7 defined as following: This gene plays a role in both autophagy and the transport of cytoplasmic molecules to vacuoles.. ER defined as following: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed). ethanol defined as following: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.. macroautophagy defined as following: The major inducible pathway for the general turnover of cytoplasmic constituents in eukaryotic cells, it is also responsible for the degradation of active cytoplasmic enzymes and organelles during nutrient starvation. Macroautophagy involves the formation of double-membrane-bounded autophagosomes which enclose the cytoplasmic constituent targeted for degradation in a membrane-bounded structure. Autophagosomes then fuse with a lysosome (or vacuole) releasing single-membrane-bounded autophagic bodies that are then degraded within the lysosome (or vacuole). Some types of macroautophagy, e.g. pexophagy, mitophagy, involve selective targeting of the targets to be degraded. [PMID:11099404, PMID:12914914, PMID:15798367, PMID:16973210, PMID:20159618, PMID:9412464]. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. insertional mutagenesis defined as following: Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation.. lysosome defined as following: A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed).. cytosolic defined as following: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.. CMA defined as following: The autophagy process which begins when chaperones and co-chaperones recognize a target motif and unfold the substrate protein. The proteins are then transported to the lysosome where they are degraded. [GOC:pad, GOC:PARL, PMID:22743996, PMID:23434281]. Cvt defined as following: Congenital severe form of flatfoot involving dislocation of the NAVICULAR BONE OF FOOT on the TALUS.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. Huntingtin defined as following: Huntingtin (3144 aa, ~348 kDa) is encoded by the human HTT gene. This protein may be involved in the regulation of vesicular transport.. atg5 defined as following: This gene plays a role in autophagy and may play a role in apoptosis.. Parkin defined as following: E3 ubiquitin-protein ligase parkin (465 aa, ~52 kDa) is encoded by the human PRKN gene. This protein may play a role in the ubiquitination of proteins targeted for proteasomal degradation.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. LC3 defined as following: A protein family whose members bind to microtubule-associated protein 1A and 1B and are involved in the formation of autophagosomes.. ATG1 defined as following: Human ULK1 wild-type allele is located in the vicinity of 12q24.3 and is approximately 29 kb in length. This allele, which encodes serine/threonine-protein kinase ULK1 protein, plays a role in both serine/threonine protein phosphorylation and the modulation of autophagy.. eukaryotic cells defined as following: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane.. HSP70 defined as following: A family of structurally related proteins that are involved in both protein folding and cellular stress responses. The members of this family are approximately 70 kDa.. macropexophagy defined as following: The selective autophagy process in which a peroxisome is degraded by macroautophagy. [GOC:autophagy, PMID:12914914, PMID:16973210]. PtdIns 4-kinases defined as following: An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.. Serine defined as following: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.. cytoplasm defined as following: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990). Htt defined as following: Human SLC6A4 wild-type allele is located in the vicinity of 17q11.2 and is approximately 42 kb in length. This allele, which encodes sodium-dependent serotonin transporter protein, plays a role in serotonin uptake. Polymorphism in the promoter region affects gene expression and lower gene expression is associated with depression. Coding region variations are associated with genetic susceptibility to both obsessive-compulsive disorder and alcoholism.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. Parkinson's disease defined as following: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75). heat shock protein 70 defined as following: A recombinant peptide that is chemically identical to or similar to the endogenous 70-kD heat shock protein (HSP70). HSP70 is a molecular chaperone that prevents physiologic stress-induced cell death by inhibiting both caspase-dependent and caspase-independent apoptosis. Because this peptide is often overexpressed in tumor cells, autologous vaccination with HSP70 derived from tumor cells may stimulate the host immune system to mount a tumoricidal cytotoxic T lymphocyte (CTL) response. (NCI04). vacuole defined as following: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. ubiquitinated proteins defined as following: Proteins covalently modified with UBIQUITINS or UBIQUITIN-LIKE PROTEINS.. PD defined as following: A score of 4 or 5 on a 5-point PET scale with an increase in intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment.. BAG3 defined as following: BAG family molecular chaperone regulator 3 (575 aa, ~62 kDa) is encoded by the human BAG3 gene. This protein is involved in both protein chaperone activity modulation and the negative regulation of apoptosis.. autophagosomes defined as following: A double-membrane-bounded compartment that engulfs endogenous cellular material as well as invading microorganisms to target them to the lytic vacuole/lysosome for degradation as part of macroautophagy. [GOC:autophagy, ISBN:0198547684, PMID:11099404]. mitochondrial defined as following: The distribution of mitochondria, including the mitochondrial genome, into daughter cells after mitosis or meiosis, mediated by interactions between mitochondria and the cytoskeleton. [GOC:mcc, PMID:10873824, PMID:11389764]. HSPB8 defined as following: Heat shock protein beta-8 (196 aa, ~22 kDa) is encoded by the human HSPB8 gene. This protein plays a role in the regulation of autophagy and as a protein chaperone.. cargo defined as following: The activity of a gene product that interacts with a cargo receptor and initiates endocytosis. [PMID:15797858]. neuronal cell death defined as following: The process of cell death in a neuron. [GOC:BHF, GOC:mah]. organelles defined as following: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the MITOCHONDRIA; the GOLGI APPARATUS; ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.. human defined as following: Members of the species Homo sapiens.. neurodegeneration defined as following: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.. fungus defined as following: Confirmatory presence of fungal microorganisms.. molecule defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. microautophagy defined as following: A type of autophagy in which the cytoplasmic entities, such as parts of CELL NUCLEI; damaged MITOCHONDRIA; and lipid droplets, are taken up by small vesicles such as VACUOLES or MULTIVESICULAR BODIES, and degraded by lysosomal digestion.. ER-phagy defined as following: The selective autohagy process in which parts of the endoplasmic reticulum are loaded into autophagosomes, delivered to the vacuole, and degraded in response to changing cellular conditions. [GOC:autophagy, GOC:dph, PMID:22481944, PMID:24060720, PMID:26040717].", "label": "yes"} {"id": "converted_47", "sentence1": "Is Weaver syndrome similar to Sotos?", "sentence2": "Overgrowth conditions are a heterogeneous group of disorders characterised by increased growth and variable features, including macrocephaly, distinctive facial appearance and various degrees of learning difficulties and intellectual disability. Among them, Sotos and Weaver syndromes are clinically well defined and due to heterozygous mutations in NSD1 and EZH2, respectively. NSD1 and EZH2 are both histone-modifying enzymes, NSD1 and EZH2 are SET domain-containing histone methyltransferases that play key roles in the regulation of transcription through histone modification and chromatin modeling: NSD1 preferentially methylates lysine residue 36 of histone 3 (H3K36) and is primarily associated with active transcription, while EZH2 shows specificity for lysine residue 27 (H3K27) and is associated with transcriptional repression, Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap, Clinically, Weaver syndrome is closely related to Sotos syndrome, which is frequently caused by mutations in NSD1, Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia., Thus, it is not surprising that prenatal overgrowth occurs in several syndromes, including the Sotos and Weaver syndromes., NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes., We conclude therefore that NSD1 mutations account for most cases of Sotos syndrome and a significant number of Weaver syndrome cases in our series., We conclude that intragenic mutations of NSD1 are the major cause of Sotos syndrome and account for some Weaver syndrome cases but rarely occur in other childhood overgrowth phenotypes., Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia, NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes, We conclude that intragenic mutations of NSD1 are the major cause of Sotos syndrome and account for some Weaver syndrome cases but rarely occur in other childhood overgrowth phenotypes, Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. , Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes., Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia. Two previous cases of neuroblastoma have been reported in children with Weaver syndrome., Weaver syndrome is closely related to Sotos syndrome,, Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia., Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident., Clinically, Weaver syndrome is closely related to Sotos syndrome, which is frequently caused by mutations in NSD1.[SEP]Relations: Sotos syndrome has relations: disease_protein with SETD2, disease_protein with SETD2, disease_disease with Malan overgrowth syndrome, disease_disease with Malan overgrowth syndrome, disease_disease with chromosomal disease with overgrowth, disease_disease with chromosomal disease with overgrowth, disease_protein with NRK, disease_protein with NRK. Weaver syndrome has relations: disease_disease with overgrowth syndrome, disease_disease with overgrowth syndrome. Definitions: EZH2 defined as following: Histone-lysine N-methyltransferase EZH2 (746 aa, ~85 kDa) is encoded by the human EZH2 gene. This protein is involved in the regulation of chromatin modification.. H3K27 defined as following: The lysine residue found at amino acid position 28 in the histone H3 protein. Methylation of this residue may be a marker for transcriptionally repressed genes.. NSD1 defined as following: Histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific (2696 aa, ~297 kDa) is encoded by the human NSD1 gene. This protein is involved in histone methylation.. neuroblastoma defined as following: A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51). histone modification defined as following: The covalent alteration of one or more amino acid residues within a histone protein. [GOC:krc]. SET defined as following: Terminology associated with the environmental setting codelist of the Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model (SDTM).. neoplasia defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. Beckwith-Wiedemann syndrome defined as following: A syndrome of multiple defects characterized primarily by umbilical hernia (HERNIA, UMBILICAL); MACROGLOSSIA; and GIGANTISM; and secondarily by visceromegaly; HYPOGLYCEMIA; and ear abnormalities.. lysine defined as following: An essential amino acid. It is often added to animal feed.. Weaver syndrome defined as following: A rare syndrome caused by mutations in the EZH2 gene, and rarely mutations in the NSD1 gene. It is characterized by advanced bone age, foot deformities, permanently bent joints, macrocephaly, flattened back of the head, a broad forehead, hypertelorism, large, low-set ears, micrognathia, delayed development of motor skills, and mild intellectual disability.. macrocephaly defined as following: A congenital abnormality in which the occipitofrontal circumference is greater than two standard deviations above the mean for a given age. It is associated with HYDROCEPHALUS; SUBDURAL EFFUSION; ARACHNOID CYSTS; or is part of a genetic condition (e.g., ALEXANDER DISEASE; SOTOS SYNDROME).. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. intellectual disability defined as following: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28).", "label": "yes"} {"id": "converted_1502", "sentence1": "Can Alzheimer's disease related miRNAs be detected in patients' blood?", "sentence2": "miRNAs are aberrantly expressed in AD, and these have been implicated in the regulation of amyloid-β (Aβ) peptide, tau, inflammation, cell death, and other aspects which are the main pathomechanisms of AD. In addition, regulation of miRNAs varies in blood, and cerebral spinal fluid may indicate alterations in AD., miRNA microarray analysis was carried out on blood of rats at 1 week and 2 months after injection. RESULTS: Many up- and downregulated miRNAs were detected., Blood miRNAs could be useful as biomarkers for exposure to nanoparticles. miR-298 regulates β-amyloid (Aβ) precursor protein-converting enzyme-1 (BACE1) in Alzheimer's disease., We previously studied microRNAs (miRNAs) in AD autopsy brain samples and reported a connection between miR-137, -181c, -9, -29a/b and AD, through the regulation of ceramides. In this study, the potential role of these miRNAs as diagnostic markers for AD was investigated. We identified that these miRNAs were down-regulated in the blood serum of probable AD patients. , 287 with Alzheimer disease (AD) as compared with 344 age- and gender-matched controls. In addition, we evaluated expression levels of hnRNP-A1 and its regulatory microRNA (miR)-590-3p in blood cells from patients and controls., Decreased relative expression levels of hsa-miR-590-3p was observed in patients with AD versus controls (0.685 ± 0.080 versus 0.931 ± 0.111, p = 0.079), and correlated negatively with hnRNP-A1 mRNA levels (r = -0.615, p = 0.0237)., expression analysis of Sp1 and its regulatory microRNAs (hsa-miR-29b and hsa-miR-375) has been performed in peripheral blood mononuclear cells (PBMCs), together with Sp1 protein analysis., Significantly decreased relative expression levels of hsa-miR-29b, but not of hsa-miR-375, were observed in AD patients, Sp1 and its regulatory hsa-miR-29b are deregulated in AD patients, possibly leading to aberrant production of downstream target genes involved in the pathogenesis. , We previously observed that miR-137, -181c, -9, and 29a/b post-transcriptionally regulate SPT levels, and the corresponding miRNA levels in the blood sera are potential diagnostic biomarkers for AD. Here, we observe a negative correlation between cortical Aβ42 and sera Aβ42, and a positive correlation between cortical miRNA levels and sera miRNA levels suggesting their potential as noninvasive diagnostic biomarkers.[SEP]Relations: Alzheimer disease has relations: disease_protein with MIR100, disease_protein with MIR100, disease_protein with MIR708, disease_protein with MIR708, disease_protein with MIR766, disease_protein with MIR766, disease_protein with MIR296, disease_protein with MIR296, disease_protein with MIR505, disease_protein with MIR505. Definitions: tau defined as following: A synthetic uridine pro-drug that is converted to uridine in vivo. Uridine, a pyrimidine nucleotide, has been used in a variety of diseases including depressive disorders and inherited myopathies. (NCI04). peripheral blood mononuclear cells defined as following: A peripheral blood cell with a single nucleus. This category includes lymphocytes and monocytes.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. BACE1 defined as following: Beta-secretase 1 (501 aa, ~56 kDa) is encoded by the human BACE1 gene. This protein plays a role in the proteolysis of ectodomains of membrane proteins.. blood cells defined as following: The cells found in the body fluid circulating throughout the CARDIOVASCULAR SYSTEM.. rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. miRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. hsa-miR-375 defined as following: This gene plays a role in gene silencing.. cortical defined as following: The outer layer of the adrenal gland. It is derived from MESODERM and comprised of three zones (outer ZONA GLOMERULOSA, middle ZONA FASCICULATA, and inner ZONA RETICULARIS) with each producing various steroids preferentially, such as ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and ANDROSTENEDIONE. Adrenal cortex function is regulated by pituitary ADRENOCORTICOTROPIN..", "label": "yes"} {"id": "converted_3830", "sentence1": "Should tirilazad be used for treatment of ischemic stroke?", "sentence2": "CONCLUSION: Tirilazad had no effect on clinical outcome but did decrease symptomatic vasospasm in five trials of aneurysmal SAH. , Tirilazad did not significantly decrease unfavorable clinical outcome on the GOS (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.89-1.20) or cerebral infarction (OR 1.04, 95% CI 0.89-1.22). , The authors investigated whether the lack of effect of tirilazad on clinical outcome in patients with acute ischemic stroke is explained by failure of tirilazad to reduce infarct volume. , Tirilazad did not alter early case fatality (odds ratio [OR] 1.11, 95% confidence interval [CI] 0.79 to 1.56) or end-of-trial case fatality (OR 1.12, 95% CI 0.88 to 1.44). A just-significant increase in death and disability, assessed as either the expanded Barthel Index (OR 1.23, 95% CI 1.01 to 1.51) or Glasgow Outcome Scale (OR 1. 23, 95% CI 1.01 to 1.50) was observed., CONCLUSIONS: Tirilazad mesylate increases death and disability by about one fifth when given to patients with acute ischemic stroke. Although further trials of tirilazad are now unwarranted, analysis of individual patient data from the trials may help elucidate why tirilazad appears to worsen outcome in acute ischemic stroke.[SEP]Relations: Ischemic stroke has relations: drug_effect with Aripiprazole, drug_effect with Aripiprazole, drug_effect with Sitaxentan, drug_effect with Sitaxentan, drug_effect with Ramipril, drug_effect with Ramipril, drug_effect with Tramadol, drug_effect with Tramadol, drug_effect with Pazopanib, drug_effect with Pazopanib. Definitions: death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. cerebral infarction defined as following: The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).. GOS defined as following: A 6-item patient-reported outcome used to evaluate patient empowerment after they have received genetic counseling and testing services.. vasospasm defined as following: spasm of the blood vessels resulting in decrease in their caliber.. ischemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue..", "label": "no"} {"id": "converted_1392", "sentence1": "Do RNA:DNA hybrids preferentially form in high or low GC regions?", "sentence2": "Intrinsic termination signals for multisubunit bacterial RNA polymerases (RNAPs) encode a GC-rich stem-loop structure followed by a polyuridine [poly(U)] tract, and it has been proposed that steric clash of the stem-loop with the exit pore of the RNAP imposes a shearing force on the RNA in the downstream RNA:DNA hybrid, resulting in misalignment of the active site, We have observed that transcription through the GC-rich FMR1 5'UTR region favors R-loop formation, with the nascent (G-rich) RNA forming a stable RNA:DNA hybrid with the template DNA strand, thereby displacing the non-template DNA strand., Transcription termination by bacterial RNA polymerase (RNAP) occurs at sequences coding for a GC-rich RNA hairpin followed by a U-rich tract. We used single-molecule techniques to investigate the mechanism by which three representative terminators (his, t500, and tR2) destabilize the elongation complex (EC)., In the 5' flanking region, nucleotides -234 to -213 encompass a GC-rich region which exhibits high homology (greater than 70%) to the 5' flanking regions of the genes of all the apolipoproteins published to date, namely, apo-A-II (-497 to -471), apo-A-I (approximately -196 to -179), apo-E (-409 to -391), and apo-C-III (approximately -116 to -103)., Recently, we demonstrated that cotranscriptional RNA•DNA hybrids are preferentially formed at GC-rich trinucleotide and tetranucleotide repeat sequences in vitro as well as in human genomic DNA., Considering the extent of transcription through the human genome as well as the abundance of GC-rich and/or non-canonical DNA structure forming tandem repeats, RNA•DNA hybrids may represent a common mutagenic conformation., Recently, we demonstrated that cotranscriptional RNA•DNA hybrids are preferentially formed at GC-rich trinucleotide and tetranucleotide repeat sequences in vitro as well as in human genomic DNA. [SEP]Relations: apolipoprotein binding has relations: molfunc_protein with VLDLR, molfunc_protein with VLDLR, molfunc_protein with MTTP, molfunc_protein with MTTP, molfunc_protein with LPA, molfunc_protein with LPA, molfunc_protein with LPL, molfunc_protein with LPL, molfunc_protein with MAPT, molfunc_protein with MAPT. Definitions: apo-E defined as following: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.. RNA defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). nucleotides defined as following: The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed). apolipoproteins defined as following: Major structural proteins of triacylglycerol-rich LIPOPROTEINS. There are two forms, apolipoprotein B-100 and apolipoprotein B-48, both derived from a single gene. ApoB-100 expressed in the liver is found in low-density lipoproteins (LIPOPROTEINS, LDL; LIPOPROTEINS, VLDL). ApoB-48 expressed in the intestine is found in CHYLOMICRONS. They are important in the biosynthesis, transport, and metabolism of triacylglycerol-rich lipoproteins. Plasma Apo-B levels are high in atherosclerotic patients but non-detectable in ABETALIPOPROTEINEMIA.. FMR1 defined as following: This gene may be involved in the regulation of mRNA trafficking.. homology defined as following: A gene from one species which corresponds to a gene in another species and that is related via a common ancestral species. These genes retain a similar sequence and function.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"} {"id": "converted_2661", "sentence1": "Has rituximab been considered as a treatment for chronic fatigues syndrome? (November 2017)", "sentence2": " The use of rintatolimod and rituximab as well as counselling, behavioural and rehabilitation therapy programs may be of benefit for CFS/ME, but the evidence of their effectiveness is still limited. [SEP]Relations: Rituximab has relations: drug_drug with Rilotumumab, drug_drug with Rilotumumab, drug_drug with Fremanezumab, drug_drug with Fremanezumab, drug_drug with Seribantumab, drug_drug with Seribantumab, drug_drug with Parsatuzumab, drug_drug with Parsatuzumab, drug_drug with Alemtuzumab, drug_drug with Alemtuzumab. Definitions: rintatolimod defined as following: A synthetic derivative of inosinic acid with antiretroviral and immunomodulatory properties. Atvogen acts through a number of pathways to stimulate intracellular antiviral activity of the immune system: it stimulates interferon production; activates the oligoadenylate synthase-RNase L pathway; stimulates natural killer cell activity; and acts as a non-mitogenic stimulator of the immune system. This agent also inhibits replication of human immunodeficiency virus (HIV) in vitro. (NCI04). rituximab defined as following: A murine-derived monoclonal antibody and ANTINEOPLASTIC AGENT that binds specifically to the CD20 ANTIGEN and is used in the treatment of LEUKEMIA; LYMPHOMA and RHEUMATOID ARTHRITIS..", "label": "yes"} {"id": "converted_821", "sentence1": "Is K-63 linked protein ubiquitination related to proteasomal degradation?", "sentence2": "In contrast to K48-linked polyubiquitin chains, K63-linked polyubiquitin chains function in nonproteasomal biological processes., Modification of proteins by the addition of lysine (K)-63-linked polyubiquitin (polyUb) chains is suggested to play important roles in a variety of cellular events, including DNA repair, signal transduction, and receptor endocytosis. , Ubiquitination is best known for its role in targeting proteins for degradation by the proteasome, but evidence of the nonproteolytic functions of ubiquitin is also rapidly accumulating. One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism. Some TRAF proteins, such as TRAF2 and TRAF3, have recently been shown to have a positive role in the canonical pathway that activates nuclear factor kappaB (NF-kappaB) through IkappaB kinase beta (IKKbeta), but a negative role in the noncanonical pathway that activates NF-kappaB through IKKalpha. These opposing roles of TRAF proteins may be linked to their ability to synthesize distinct forms of polyubiquitin chains. Indeed, the TRAF2-interacting protein RIP can mediate IKK activation when it is modified by K(63) polyubiquitin chains, but is targeted to degradation by the proteasome when it is K(48)-polyubiquitinted by the NF-kappaB inhibitor A20. Thus, ubiquitin chains are dynamic switches that can influence signaling outputs in dramatically different ways., Importantly, although Lys-48-linked ubiquitin chains appear to trigger proteasomal degradation, the presence of Lys-63-linked ubiquitin chains suggests that ubiquitination of IP(3)Rs may have physiological consequences beyond signaling for degradation., Chains of ubiquitin linked via lysine 48 (K48) are associated with protein degradation while chains linked via lysine 63 (K63) are associated with intracellular signaling., Lys(48)-linked chains target proteins for proteasomal degradation, and Lys(63)-linked chains function in signal transduction, endocytosis and DNA repair, Remarkably, the attached Lys-48- and Lys-63-linked ubiquitin chains are homogeneous and are segregated to separate IP(3)R subunits, and Lys-48-linked ubiquitin chains, but not Lys-63-linked chains, are required for IP(3)R degradation, Activated inositol 1,4,5-trisphosphate receptors are modified by homogeneous Lys-48- and Lys-63-linked ubiquitin chains, but only Lys-48-linked chains are required for degradation.[SEP]Relations: ubiquitin-ubiquitin ligase activity has relations: molfunc_protein with UBR5, molfunc_protein with UBR5, molfunc_protein with UBOX5, molfunc_protein with UBOX5, molfunc_protein with STUB1, molfunc_protein with STUB1, molfunc_protein with PRPF19, molfunc_protein with PRPF19, molfunc_protein with PPIL2, molfunc_protein with PPIL2. Definitions: proteasome defined as following: A large multisubunit complex which catalyzes protein degradation, found in eukaryotes, archaea and some bacteria. In eukaryotes, this complex consists of the barrel shaped proteasome core complex and one or two associated proteins or complexes that act in regulating entry into or exit from the core. [GOC:rb, Wikipedia:Proteasome]. IKK defined as following: Catalysis of the reaction: ATP + IkappaB protein = ADP + IkappaB phosphoprotein. [EC:2.7.11.10]. lysine defined as following: An essential amino acid. It is often added to animal feed.. nuclear factor kappaB defined as following: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. TRAF2 defined as following: TNF receptor-associated factor 2 (501 aa, ~56 kDa) is encoded by the human TRAF2 gene. This protein is involved in antibody isotype switching, protein ubiquitination, tumor necrosis factor receptor-dependent signaling, and the regulation of apoptosis.. TRAF3 defined as following: A signal transducing tumor necrosis factor receptor associated factor that is involved in regulation of NF-KAPPA B signaling and activation of MITOGEN-ACTIVATED PROTEIN KINASES.. RIP defined as following: Receptor-interacting serine/threonine-protein kinase 1 (671 aa, ~76 kDa) is encoded by the human RIPK1 gene. This protein plays a role in signaling that mediates inflammation, serine/threonine phosphorylation and cell death.. modified defined as following: The act of alteration or modification; changed or altered in form or character.. protein kinase defined as following: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.. Modification defined as following:Respond with exceptions, completions and modifications or revisions done before completion
. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species..", "label": "no"} {"id": "converted_296", "sentence1": "is intense physical activity associated with longevity ?", "sentence2": "We found a very significant increase in average longevity (17%) of the cyclists when compared with the general population. The age at which 50% of the general population died was 73.5 vs. 81.5 years in Tour de France participants. Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners., Competitive exercise does not induce cardiac damage in individuals with healthy hearts, but does induce physiological functional and structural cardiac adaptations which have positive effects on life expectancy., Medallists lived an average of 2.8 years longer than controls. Medallists in eight of the nine country groups had a significant survival advantage compared with controls. Gold, silver, and bronze medallists each enjoyed similar sized survival advantages. Medallists in endurance sports and mixed sports had a larger survival advantage over controls at 30 years (1.13, 1.09 to 1.17; 1.11, 1.09 to 1.13) than that of medallists in power sports (1.05, 1.01 to 1.08). CONCLUSIONS: Olympic medallists live longer than the general population, irrespective of country, medal, or sport. This study was not designed to explain this effect, but possible explanations include genetic factors, physical activity, healthy lifestyle, and the wealth and status that come with international sporting glory., Long-term endurance training induces in elderly subjects an increased HRV and a higher exercise working capacity, which are well-established predictors of cardiovascular and overall mortality., Sports activity in adolescents and young adults was associated with an increased risk of SD, both in males and females. Sports, per se, was not a cause of the enhanced mortality, but it triggered SD in those athletes who were affected by cardiovascular conditions predisposing to life-threatening ventricular arrhythmias during physical exercise.[SEP]Relations: SLC17A5 has relations: molfunc_protein with transmembrane transporter activity, molfunc_protein with transmembrane transporter activity, molfunc_protein with carbohydrate:proton symporter activity, molfunc_protein with carbohydrate:proton symporter activity. Ventricular arrhythmia has relations: drug_effect with Ganciclovir, drug_effect with Ganciclovir, drug_effect with Sildenafil, drug_effect with Sildenafil. Silver has relations: drug_effect with Inflammatory abnormality of the skin, drug_effect with Inflammatory abnormality of the skin. Definitions: ventricular arrhythmias defined as following: A disorder characterized by an electrocardiographic finding of an atypical cardiac rhythm resulting from a pathologic process in the cardiac ventricles.. Sports defined as following: Activities or games, usually involving physical effort or skill. Reasons for engagement in sports include pleasure, competition, and/or financial reward..", "label": "yes"} {"id": "converted_1486", "sentence1": "Does ventriculoperitoneal shunt improve normal pressure hydrocephalus?", "sentence2": "Clinical improvement depends not only on the capability to restore the cerebrospinal fluid dynamic, but also on the ability of cerebral parenchyma to recover the metabolic function., After shunting, the global CMRglu significantly increased (2.95 ± 0.44 vs 4.38 ± 0.68, p = 10(-7)) in all INPH patients with a mean percentage value of 48.7%. , Our preliminary data show that changes in the CMRglu are promptly reversible after surgery and that there is a relationship between the early metabolic changes and clinical symptoms, independently from the simultaneous changes in the ventricular size. The remarkable and prompt improvement in the global CMRglu and in symptoms may also have important implications for the current concept of \"neuronal plasticity\" and for the cells' reactivity in order to recover their metabolic function., Outcome of shunting in INPH is most often successful when patients are accurately diagnosed, suitably evaluated for surgical candidacy, and managed carefully throughout the preoperative, surgical, and postoperative periods., The decision to perform the only efficient procedure, i.e., a ventricular shunt operation, depends upon a number of established arguments in favor of that procedure. Clinical improvement, which is often spectacular, can then confirm the diagnosis. , During the 1st postoperative year, there was improvement in the condition of 22 patients (96%) who had received a ventricular shunt; 21 of these patients (91%) remained improved until death or for at least 5 years., Shunt treatment showed an effect on cognitive functions of distractibility of attention and motor speed, but not on intelligence of memory. Three patients deteriorated, eleven remained stable and sixteen showed significant improvement on psychological tests, mainly those for attention, motor speed and memory, but rarely did any improvement of intelligence occur.[SEP]Relations: Cessation of head growth has relations: phenotype_phenotype with Secondary microcephaly, phenotype_phenotype with Secondary microcephaly, disease_phenotype_positive with Angelman syndrome due to a point mutation, disease_phenotype_positive with Angelman syndrome due to a point mutation, disease_phenotype_positive with leukoencephalopathy with vanishing white matter, disease_phenotype_positive with leukoencephalopathy with vanishing white matter, disease_phenotype_positive with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, disease_phenotype_positive with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies. cerebrospinal fluid has relations: anatomy_anatomy with transudate, anatomy_anatomy with transudate. Definitions: death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. cerebrospinal fluid defined as following: A watery fluid that is continuously produced in the CHOROID PLEXUS and circulates around the surface of the BRAIN; SPINAL CORD; and in the CEREBRAL VENTRICLES..", "label": "yes"} {"id": "converted_1225", "sentence1": "Is the regulation of Vsr endonuclease independent of the growth phase of bacteria?", "sentence2": "Growth phase-dependent regulation of Vsr endonuclease, Vsr endonuclease levels are growth phase dependent., Growth phase-dependent regulation of Vsr endonuclease may contribute to 5-methylcytosine mutational hot spots in Escherichia coli., Using rabbit polyclonal antibodies, we have shown that the Dcm cytosine methylase of Escherichia coli is maintained at a constant level during cell growth, while Vsr endonuclease levels are growth phase dependent., Vsr endonuclease, which initiates very short patch repair, has been hypothesized to regulate mutation in stationary-phase cells., The efficiency of the two pathways changes during the bacterial life cycle; MMR is more efficient during exponential growth and VSP repair is more efficient during the stationary phase., Overexpression of Vsr does dramatically increase the stationary-phase reversion of a Lac- frameshift allele, but the absence of Vsr has no effect., Using rabbit polyclonal antibodies, we have shown that the Dcm cytosine methylase of Escherichia coli is maintained at a constant level during cell growth, while Vsr endonuclease levels are growth phase dependent, The efficiency of the two pathways changes during the bacterial life cycle; MMR is more efficient during exponential growth and VSP repair is more efficient during the stationary phase, Vsr endonuclease, which initiates very short patch repair, has been hypothesized to regulate mutation in stationary-phase cells[SEP]Relations: escherichia coli infection has relations: disease_phenotype_positive with Recurrent gram-negative bacterial infections, disease_phenotype_positive with Recurrent gram-negative bacterial infections. mismatch repair has relations: bioprocess_protein with RNASEH2A, bioprocess_protein with RNASEH2A, bioprocess_protein with MLH1, bioprocess_protein with MLH1, bioprocess_protein with POLD2, bioprocess_protein with POLD2, bioprocess_protein with EXO1, bioprocess_protein with EXO1. Definitions: 5-methylcytosine defined as following: A methylated form of the nucleobase cytosine occurring predominantly in cytosine-phosphate-guanine (CpG) islands that are produced by DNA methyltransferases and may regulate gene expression. Like cytosine, the DNA sequence containing 5-methylcytosine (5-mC) is able to be replicated without error and 5-mC can pair with guanine in double stranded DNA. However, DNA sequences containing a high local concentration of 5-mC may be less transcriptionally active than areas with higher ratios of unmodified cytosine.. MMR defined as following: A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the BASE PAIR MISMATCH and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001). Escherichia coli defined as following: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc..", "label": "no"} {"id": "converted_182", "sentence1": "Does thyroid hormone regulate calcium transient in the myocardium? ", "sentence2": "3-iodothyronamine (T(1)AM) is a novel endogenous relative of thyroid hormone, able to interact with trace amine-associated receptors, a class of plasma membrane G protein-coupled receptors, and to produce a negative inotropic and chronotropic effect, In adult rat cardiomyocytes acute exposure to 20 microM T(1)AM decreased the amplitude and duration of the calcium transient., In normal porcine myocardium T3 had no effect on the extent of isometric force generation but accelerated the time course of force development (p < 0.05) and increased the calcium transient (p < 0.001). After induction of myocardial depression by epinephrine exposure T3 accelerated the intracellular calcium transients and reduced diastolic calcium, The experimental data showing increased force amplitudes at unaltered amplitudes of the intracellular calcium transient and an even-reduced calcium time integral provide strong evidence for a sensitization of the contractile apparatus for calcium by triiodothyronine, hese results indicate that the thyroid state influences the time course of the calcium transient and are consistent with the abbreviation in the duration of contraction that is observed in the hyperthyroid state.[SEP]Relations: myocardial infarction has relations: contraindication with Calcium chloride, contraindication with Calcium chloride. response to thyroid hormone has relations: bioprocess_protein with GBA, bioprocess_protein with GBA, bioprocess_bioprocess with cellular response to thyroid hormone stimulus, bioprocess_bioprocess with cellular response to thyroid hormone stimulus, bioprocess_protein with SLC26A5, bioprocess_protein with SLC26A5. Liothyronine has relations: contraindication with thyroid crisis (disease), contraindication with thyroid crisis (disease). Definitions: calcium defined as following: A dietary supplement containing the mineral calcium.. epinephrine defined as following: The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.. thyroid hormone defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs.. plasma membrane defined as following: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.. triiodothyronine defined as following: A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.. myocardium defined as following: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow..", "label": "yes"} {"id": "converted_3007", "sentence1": "Can mitochondria be inherited by both parents in humans?", "sentence2": "Biparental Inheritance of Mitochondrial DNA in Humans., Although there has been considerable debate about whether paternal mitochondrial DNA (mtDNA) transmission may coexist with maternal transmission of mtDNA, it is generally believed that mitochondria and mtDNA are exclusively maternally inherited in humans. Here, we identified three unrelated multigeneration families with a high level of mtDNA heteroplasmy (ranging from 24 to 76%) in a total of 17 individuals. Heteroplasmy of mtDNA was independently examined by high-depth whole mtDNA sequencing analysis in our research laboratory and in two Clinical Laboratory Improvement Amendments and College of American Pathologists-accredited laboratories using multiple approaches. A comprehensive exploration of mtDNA segregation in these families shows biparental mtDNA transmission with an autosomal dominantlike inheritance mode. Our results suggest that, although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring. [SEP]Relations: mitochondrion has relations: cellcomp_protein with YRDC, cellcomp_protein with YRDC, cellcomp_protein with SNCA, cellcomp_protein with SNCA, cellcomp_protein with GHR, cellcomp_protein with GHR, cellcomp_protein with YWHAH, cellcomp_protein with YWHAH, cellcomp_protein with DNA2, cellcomp_protein with DNA2. Definitions: mitochondria defined as following: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed). mtDNA defined as following: Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.. heteroplasmy defined as following: The occurrence of more than one organellar GENOME in the organelle population of a cell, tissue, or individual organism. It is due to the accumulation of different mutations that occur within the population of individual organelles of a cell.. Humans defined as following: Members of the species Homo sapiens.. humans defined as following: Members of the species Homo sapiens..", "label": "yes"} {"id": "converted_3145", "sentence1": "Can TAD disruption lead to disease?", "sentence2": "its perturbation will lead to human disease, highlighting the accumulating evidence that links the diverse 3D genome architecture components to a multitude of human diseases and the emerging mechanisms by which 3D genome derangement causes disease phenotypes., TAD boundaries are insulators of genomic neighborhoods. In this issue, Sun et al. show that disease-associated tandem repeats are located to TAD boundaries and affect their insulation. , Recent studies of TAD boundaries disrupted in engineered mouse models show that boundary mutations can recapitulate human developmental disorders as a result of aberrant promoter-enhancer interactions in the affected TADs, Similar boundary disruptions in certain cancers can result in oncogene overexpression, and CTCF binding sites at boundaries appear to be hyper-mutated across cancers., the disruption of these structures by genomic rearrangements can result in gene misexpression and disease., TAD disruption as oncogenic driver., Recent studies have shown that TAD disruption is often found in cancer cells and contributes to oncogenesis through two mechanisms., Disruption of TAD boundaries results in aberrant gene expression by exposing genes to inappropriate regulatory elements., However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary rearrangements can alter gene expression., Disruption of this organization by structural variations can lead to ectopic interactions between enhancers and promoters, and to alteration of genes expression patterns., Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers., Deletion in 2q35 excluding the IHH gene leads to fetal severe limb anomalies and suggests a disruption of chromatin architecture., We demonstrate that disruption of TADs can rewire long-range regulatory architecture and result in pathogenic phenotypes. , Disruption of TAD boundaries results in aberrant gene expression by exposing genes to inappropriate regulatory elements. , Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers. , Disruption of a TAD boundary causes ectopic chromosomal contacts and long-range transcriptional misregulation. , Recent studies of TAD boundaries disrupted in engineered mouse models show that boundary mutations can recapitulate human developmental disorders as a result of aberrant promoter-enhancer interactions in the affected TADs. , Recent studies have shown that TAD disruption is often found in cancer cells and contributes to oncogenesis through two mechanisms. , Disruption of this organization by structural variations can lead to ectopic interactions between enhancers and promoters, and to alteration of genes expression patterns. , Similar boundary disruptions in certain cancers can result in oncogene overexpression, and CTCF binding sites at boundaries appear to be hyper-mutated across cancers. , However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary rearrangements can alter gene expression. [SEP]Relations: Abnormality of the dentition has relations: disease_phenotype_positive with intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome, disease_phenotype_positive with intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome, disease_phenotype_positive with Marshall syndrome, disease_phenotype_positive with Marshall syndrome, disease_phenotype_positive with severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome, disease_phenotype_positive with severe intellectual disability-short stature-behavioral abnormalities-facial dysmorphism syndrome, disease_phenotype_positive with SIN3A-related intellectual disability syndrome due to a point mutation, disease_phenotype_positive with SIN3A-related intellectual disability syndrome due to a point mutation, disease_phenotype_positive with late-onset localized junctional epidermolysis bullosa-intellectual disability syndrome, disease_phenotype_positive with late-onset localized junctional epidermolysis bullosa-intellectual disability syndrome. Definitions: TADs defined as following: Tietz syndrome is a genetic hypopigmentation and deafness syndrome characterized by congenital profound bilateral sensorineural hearing loss and generalized albino-like hypopigmentation of skin, eyes and hair.. cancer cells defined as following: Cells of, or derived from, a malignant tumor.. pathogenic defined as following: A genetic variant that is known to directly contribute to the development of disease.. genome defined as following: Anatomical set of genes in all the chromosomes.. human defined as following: Members of the species Homo sapiens.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. promoters defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. oncogene defined as following: Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of \"v-\" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix \"c-\" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.. IHH gene defined as following: This gene is involved in growth, patterning and morphogenesis..", "label": "yes"} {"id": "converted_3529", "sentence1": "Are CD8+ (cytotoxic) T cells and CD4+ Helper T cells generated in the thyroid and express the T-cell receptor?", "sentence2": "A fundamental question in developmental immunology is how bipotential thymocyte precursors generate both CD4+ helper and CD8+ cytotoxic T cell lineages., CD4+CD8+ progenitor thymocytes undergo selection following interaction with MHC class I and class II molecules bearing peptide self-antigens, giving rise to CD8+ cytotoxic and CD4+ helper or regulatory T cell lineages, respectively., Through positive selection, double-positive cells in the thymus differentiate into CD4(+) or CD8(+) T single-positive cells that subsequently develop into different types of effective T cells, such as T-helper and cytotoxic T lymphocyte cells,, Development, differentiation, and function of thymocytes and CD4(+) and CD8(+) T cells are controlled by a multitude of secreted and intracellular factors, . The CD4(+) helper versus CD8(+) cytotoxic T-cell fate decision serves as an excellent model to study binary fate decision processes. These two cell types are derived from common precursors in the thymus., Signals elicited by binding of the T-cell antigen receptor and the CD4/CD8 co-receptor to major histocompatibility complex (MHC) molecules control the generation of CD4+ (helper) or CD8+ (cytotoxic) T cells from thymic precursors that initially express both co-receptor proteins., In the thymus, mature CD4+CD8- and CD4-CD8+ T cells expressing alpha beta T-cell antigen receptors (TCR) develop from immature thymocytes through CD4+CD8+ alpha beta TCR+ intermediates., In the thymus, immature CD8(-4)-TCR- cells differentiate, possibly via a short stage of CD8+4- thymocytes, into CD8+4+ TCR+ T cells and mature further into the main T cell populations, the CD8+4- TCR+ cytotoxic T lymphocytes and the CD4+8- TCR+ T helper cells., In the mammalian thymus, CD4 helper T cells and CD8 cytotoxic T cells arise from a common precursor that expresses both CD4 and CD8.[SEP]Relations: T cell receptor complex has relations: cellcomp_protein with CD4, cellcomp_protein with CD4, cellcomp_protein with CD8B, cellcomp_protein with CD8B, cellcomp_protein with CD8A, cellcomp_protein with CD8A, cellcomp_protein with CD3E, cellcomp_protein with CD3E, cellcomp_protein with CD3D, cellcomp_protein with CD3D. Definitions: T cells defined as following: A subset of therapeutic autologous T-lymphocytes that express a T-cell receptor (TCR) composed of one gamma chain and one delta chain, with potential immunomodulating and antineoplastic activities. Upon administration of the therapeutic gamma delta T-lymphocytes, these cells secrete interferon-gamma (IFN-g), and exert direct killing of tumor cells. In addition, these cells activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response against tumor cells. Gamma delta T-lymphocytes play a key role in the activation of the immune system and do not require major histocompatibility complex (MHC)-mediated antigen presentation to exert their cytotoxic effect.. thymocytes defined as following: HEMATOPOIETIC PROGENITOR CELLS that have migrated to the THYMUS where they differentiate into T-LYMPHOCYTES. Thymocytes are classified into maturational stages based on the expression of CELL SURFACE ANTIGENS.. CD8 defined as following: Human CD8A wild-type allele is located in the vicinity of 2p11.2 and is approximately 24 kb in length. This allele, which encodes T-cell surface glycoprotein CD8 alpha chain protein, plays a role in antigen recognition by T-cells.. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. MHC defined as following: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. T cell defined as following: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.. TCR defined as following: The nucleotide-excision repair process that carries out preferential repair of DNA lesions on the actively transcribed strand of the DNA duplex. In addition, the transcription-coupled nucleotide-excision repair pathway is required for the recognition and repair of a small subset of lesions that are not recognized by the global genome nucleotide excision repair pathway. [PMID:10197977, PMID:11900249]. CD4 defined as following: T-cell surface glycoprotein CD4 (458 aa, ~51 kDa) is encoded by the human CD4 gene. This protein plays a role in antigen recognition and HIV entry.. T-cell antigen receptor defined as following: Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (CD3 COMPLEX). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.. molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. thymus defined as following: A plant genus of the family LAMIACEAE best known for the thyme spice added to foods.. T-cell receptor defined as following: Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (CD3 COMPLEX). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains..", "label": "no"} {"id": "converted_4214", "sentence1": "Are there antimicrobial proteins in royal jelly?", "sentence2": "Jellein, a peptide derived from royal jelly of honeybee has been shown to have promising effect against several bacterial and fungal species. , It is also the most studied bee product, aimed at unravelling its bioactivities, such as antimicrobial, antioxidant, anti-aging, immunomodulatory, and general tonic action against laboratory animals, microbial organisms, farm animals, and clinical trials, Jelleines, isolated as novel antibacterial peptides from the Royal Jelly (RJ) of bees, exhibit broad-spectrum protection against microbial infections., The study showed significant antimicrobial activity from several proteins present in the honey of M. beecheii.[SEP]Relations: bacterial arthritis has relations: disease_protein with IFNG, disease_protein with IFNG, disease_protein with TNF, disease_protein with TNF, disease_disease with gonococcal infection of joint, disease_disease with gonococcal infection of joint, disease_disease with infectious disease, disease_disease with infectious disease, disease_disease with infective arthritis, disease_disease with infective arthritis. Definitions: peptide defined as following: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein..", "label": "yes"} {"id": "converted_3231", "sentence1": "Is CD63 an exosomal marker?", "sentence2": "f exosome marker proteins (e.g., CD63, Alix) , CD63 levels and acetylcholinesterase (AChE) activity were used as markers of exosome,, The results demonstrated these exosomes all expressed CD9, CD63, CD81, Alix[SEP]Relations: PDCD6IP has relations: protein_protein with CD2AP, protein_protein with CD2AP, protein_protein with SH3GL3, protein_protein with SH3GL3, bioprocess_protein with positive regulation of exosomal secretion, bioprocess_protein with positive regulation of exosomal secretion, protein_protein with LGALS3, protein_protein with LGALS3, protein_protein with ARRDC3, protein_protein with ARRDC3. Definitions: exosome defined as following: A type of extracellular vesicle, containing RNA and proteins, that is secreted into the extracellular space by EXOCYTOSIS when MULTIVESICULAR BODIES fuse with the PLASMA MEMBRANE.. CD63 defined as following: Ubiquitously-expressed tetraspanin protein that is found in late ENDOSOMES and LYSOSOMES. It functions in intracellular protein transport and signaling.. CD81 defined as following: A tetraspanin protein that is involved in a variety of cellular functions including BASEMENT MEMBRANE assembly, and in the formation of a molecular complexes on the surface of LYMPHOCYTES.. CD9 defined as following: A subtype of tetraspanin protein that plays a role in cell adhesion, cell motility, and tumor metastasis. It functions in platelet activation and aggregation, the formation of paranodal junctions in neuronal tissue, and the fusion of sperm with egg..", "label": "yes"} {"id": "converted_2492", "sentence1": "Are patients with Sjogren syndrome at increased risk for lymphoma?", "sentence2": "The heightened risk of non-Hodgkin lymphoma (NHL) development in primary Sjogren syndrome (SS) is well established., Primary Diffuse Large B-Cell Lymphoma of the Liver in a Patient with Sjogren Syndrome., Immunohistochemical and molecular features of the tumors allowed diagnosis of diffuse large B-cell lymphoma (DLBCL). , To our knowledge, the patient described here represents the first reported case of DLBCL with primary liver involvement in SS., Rituximab is also effective in the treatment of SS-associated (extrasalivary) lymphomas, although the therapeutic response in salivary lymphoma is poorer., Rituximab treatment for Sjogren syndrome-associated non-Hodgkin's lymphoma: case series., Five per cent of patients with primary Sjogren's syndrome (pSS) develop malignant non-Hodgkin's lymphoma (NHL), usually of the mucosa-associated lymphoid tissue (MALT) and most frequently located in the major salivary glands. , [A case of Sjogren syndrome coexistent with MALT lymphoma occurring along the parotid gland and trachea]., Both histological examinations revealed MALT-type marginal zone B-cell lymphoma. , In the majority of patients, it is a late event and frequently associated with systemic disease or risk factors for lymphoma development., The incidence of lymphoma is higher in patients with Sjögren's syndrome than in the general population., Among the clinical and serological parameters that have been associated with lymphoma development in SS patients, the presence of palpable purpura, low C4, and mixed monoclonal cryoglobulinemia constitute the main predictive markers, and patients displaying these risk factors should be monitored closely., A case of pulmonary pseudolymphoma and Sjogren syndrome is presented., Furthermore, RA, Sjögren's syndrome, systemic lupus erythematosus, and possibly celiac disease may share an association with risk of diffuse large B-cell lymphoma, in addition to well-established links of Sjögren's syndrome with risk of mucosa-associated lymphoid tissue lymphoma and of celiac disease with risk of small intestinal lymphoma., Predicting the risk for lymphoma development in Sjogren syndrome: An easy tool for clinical use., Lymphoma is a very severe complication of primary Sjögren's syndrome: 5 to 10% of patients followed for more than 10 years will develop a lymphoma., Hematologic manifestations and predictors of lymphoma development in primary Sjögren syndrome: clinical and pathophysiologic aspects., Recent results clearly indicate an association between severity of chronic inflammation and lymphoma risk in RA and Sjögren's syndrome., Several autoimmune diseases, including primary Sjögren's syndrome (pSS), are associated with an increased risk for lymphoma., Primary Sjogren's syndrome (pSS) confers increased risk for non-Hodgkin lymphoma (NHL) development., Furthermore, we review the emerging role of ELS and lymphoid chemokines in driving extranodal B cell lymphomagenesis in SS and we focus on recent evidence suggesting that ELS identify subsets of SS patients at increased risk of developing systemic manifestations and lymphoma., Sjogren's syndrome (SS) is a chronic autoimmune disorder with the highest risk for lymphoma development among all autoimmune diseases., In contrast to secondary SS, the risk for developing non-Hodgkin's lymphoma is highly increased in patients with primary SS., Predicting the risk for lymphoma development in Sjogren syndrome: An easy tool for clinical use., Primary Sjogren's syndrome (pSS) is complicated by B-cell lymphoma in 5-10% of patients., Patients with Sjögren syndrome are at increased risk of lymphoma development., Sjogren's syndrome is an autoimmune disease with a known predisposition for lymphoma development., Certain autoimmune and chronic inflammatory conditions, such as Sjögren's syndrome and rheumatoid arthritis (RA), have consistently been associated with an increased risk of malignant lymphomas, but it is unclear whether elevated lymphoma risk is a phenomenon that accompanies inflammatory conditions in general.[SEP]Relations: Sjogren syndrome has relations: disease_phenotype_positive with Lymphoma, disease_phenotype_positive with Lymphoma, disease_phenotype_positive with Lymphadenopathy, disease_phenotype_positive with Lymphadenopathy, disease_phenotype_positive with Increased circulating antibody level, disease_phenotype_positive with Increased circulating antibody level, disease_phenotype_positive with Behavioral abnormality, disease_phenotype_positive with Behavioral abnormality. Lymphoma has relations: disease_phenotype_positive with Sjogren syndrome, disease_phenotype_positive with Sjogren syndrome. Definitions: DLBCL defined as following: Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation.. NHL defined as following: Malignant lymphoma in which the majority of neoplastic cells within the follicles are large cleaved or noncleaved cells. The degree to which the follicular center cells retain their ability to form follicles varies with the state of B-cell transformation.. MALT lymphoma defined as following: Extranodal lymphoma of lymphoid tissue associated with mucosa that is in contact with exogenous antigens. Many of the sites of these lymphomas, such as the stomach, salivary gland, and thyroid, are normally devoid of lymphoid tissue. They acquire mucosa-associated lymphoid tissue (MALT) type as a result of an immunologically mediated disorder.. RA defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. B-cell lymphoma defined as following: A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.. primary Sjogren's syndrome defined as following: Sjogren syndrome without a concomitant systemic autoimmune disorder.. lymphoma defined as following: A general term for various neoplastic diseases of the lymphoid tissue.. SS defined as following:Supernumerary mandibular right first primary molar
. autoimmune disease defined as following: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.. mucosa-associated lymphoid tissue defined as following: Lymphoid tissue located beneath the mucosal epithelia of those mucosal surfaces that have contact with the external environment, such as the respiratory, digestive, and urinary systems. MALT consists of a collection of predominantly small lymphocytes, fewer larger, transformed lymphocytes, and plasma cells. It protects the body from pathogens that enter via the mucosa. MALT gives rise to a distinctive type of B-cell lymphoma that usually follows an indolent clinical course.. malignant non-Hodgkin's lymphoma defined as following: Any of a group of malignant tumors of lymphoid tissue that differ from HODGKIN DISEASE, being more heterogeneous with respect to malignant cell lineage, clinical course, prognosis, and therapy. The only common feature among these tumors is the absence of giant REED-STERNBERG CELLS, a characteristic of Hodgkin's disease.. systemic disease defined as following: A clinical course finding indicating that a disease presents with systemic manifestations.. Sjögren syndrome defined as following: Chronic inflammatory and autoimmune disease in which the salivary and lacrimal glands undergo progressive destruction by lymphocytes and plasma cells resulting in decreased production of saliva and tears. The primary form, often called sicca syndrome, involves both KERATOCONJUNCTIVITIS SICCA and XEROSTOMIA. The secondary form includes, in addition, the presence of a connective tissue disease, usually rheumatoid arthritis.. systemic lupus erythematosus defined as following: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.. parotid gland defined as following: The largest of the three pairs of SALIVARY GLANDS. They lie on the sides of the FACE immediately below and in front of the EAR.. pulmonary pseudolymphoma defined as following: A rare, reactive lesion in the lung parenchyma. It is characterized by the formation of a single or several nodules that are composed of lymphocytic infiltrates with reactive germinal centers.. diffuse large B-cell lymphoma defined as following: Diffuse large B-cell lymphoma that affects the kidney.. Rituximab defined as following: A murine-derived monoclonal antibody and ANTINEOPLASTIC AGENT that binds specifically to the CD20 ANTIGEN and is used in the treatment of LEUKEMIA; LYMPHOMA and RHEUMATOID ARTHRITIS.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. salivary glands defined as following: Glands that secrete SALIVA in the MOUTH. There are three pairs of salivary glands (PAROTID GLAND; SUBLINGUAL GLAND; SUBMANDIBULAR GLAND).. celiac disease defined as following: A malabsorption syndrome that is precipitated by the ingestion of foods containing GLUTEN, such as wheat, rye, and barley. It is characterized by INFLAMMATION of the SMALL INTESTINE, loss of MICROVILLI structure, failed INTESTINAL ABSORPTION, and MALNUTRITION.. pSS defined as following: A very rare genetic syndrome caused by deletions on the proximal short arm of chromosome 11. It is characterized by the presence of multiple exostoses and enlarged parietal foramina.. Sjogren syndrome defined as following: Chronic inflammatory and autoimmune disease in which the salivary and lacrimal glands undergo progressive destruction by lymphocytes and plasma cells resulting in decreased production of saliva and tears. The primary form, often called sicca syndrome, involves both KERATOCONJUNCTIVITIS SICCA and XEROSTOMIA. The secondary form includes, in addition, the presence of a connective tissue disease, usually rheumatoid arthritis..", "label": "yes"} {"id": "converted_3003", "sentence1": "Is verubecestat effective for Alzheimer’s Disease?", "sentence2": " The lack of efficacy of verubecestat in mild-to-moderate AD raises important questions about the timing of intervention with BACE-1 inhibitors, and anti-amyloid therapies in general, in AD treatment., This reaction was applied to the preparation of verubecestat, which is currently undergoing clinical evaluation for the treatment of Alzheimer's disease., Verubecestat is an inhibitor of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) being evaluated in clinical trials for the treatment of Alzheimer's disease. , CONCLUSIONS: Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events. , Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease.Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events. , CONCLUSIONS\nVerubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events., Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events.[SEP]Relations: familial Alzheimer disease has relations: disease_disease with Alzheimer disease, disease_disease with Alzheimer disease, disease_disease with inherited prion disease, disease_disease with inherited prion disease, disease_protein with PRNP, disease_protein with PRNP, disease_phenotype_positive with Sleep disturbance, disease_phenotype_positive with Sleep disturbance, disease_phenotype_positive with Perseveration, disease_phenotype_positive with Perseveration. Definitions: BACE1 defined as following: Beta-secretase 1 (501 aa, ~56 kDa) is encoded by the human BACE1 gene. This protein plays a role in the proteolysis of ectodomains of membrane proteins.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65..", "label": "no"} {"id": "converted_1334", "sentence1": "Is protein Fbw7 a SCF type of E3 ubiquitin ligase?", "sentence2": "FBW7 (F-box and WD repeat domain-containing 7) is the substrate recognition component of an evolutionary conserved SCF (complex of SKP1, CUL1 and F-box protein)-type ubiquitin ligase., However, very few E3 ubiquitin ligases are known to target G-CSFR for ubiquitin-proteasome pathway. Here we identified F-box and WD repeat domain-containing 7 (Fbw7), a substrate recognizing component of Skp-Cullin-F box (SCF) E3 ubiquitin Ligase physically associates with G-CSFR and promotes its ubiquitin-mediated proteasomal degradation., FBW7 is a crucial component of an SCF-type E3 ubiquitin ligase, which mediates degradation of an array of different target proteins., F-box and WD repeat domain-containing 7 (FBW7), the substrate-binding subunit of E3 ubiquitin ligase SCF(FBW7) (a complex of SKP1, cullin-1 and FBW7), plays important roles in various physiological and pathological processes., The tumor suppressor Fbxw7 (also known as Sel-10, hCdc4, hAgo, or Fbw7) is an F-box protein that functions as the substrate-recognition subunit of an SCF ubiquitin ligase complex and targets a group of oncoproteins for degradation. , Fbw7 is the substrate recognition component of the Skp1-Cullin-F-box (SCF)-type E3 ligase complex and a well-characterized tumor suppressor that targets numerous oncoproteins for destruction., Fbw7 is a member of F-box family proteins, which constitute one subunit of Skp1, Cul1, and F-box protein (SCF) ubiquitin ligase complex., The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase. SCF(Fbw7) facilitates polyubiquitination and subsequent degradation of various proteins such as Notch, cyclin E, c-Myc and c-Jun., Fbxw7 (also known as Fbw7, SEL-10, hCdc4, or hAgo) is the F-box protein subunit of an Skp1-Cul1-F-box protein (SCF)-type ubiquitin ligase complex that plays a central role in the degradation of Notch family members., The Fbxw7 (F-box/WD repeat-containing protein 7; also called CDC4, Sel10, Ago, and Fbw7) component of the SCF (Skp1/Cullin/F-box protein) E3 ubiquitin ligase complex acts as a tumor suppressor in several tissues and targets multiple transcriptional activators and protooncogenes for ubiquitin-mediated degradation., The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase., We demonstrate here that Fbw7 (F-box and WD repeat domain containing-7), the substrate recognition component of an SCF (complex of SKP1, CUL1 and F-box protein)-type E3 ubiquitin ligase, is a key regulator of NSC/NPC viability and differentiation., The SCF(Fbw7) ubiquitin ligase complex plays important roles in cell growth, survival, and differentiation via the ubiquitin-proteasome-mediated regulation of protein stability., F-box and WD-40 domain protein 7 (Fbw7) provides substrate specificity for the Skp1-Cullin1-F-box protein (SCF) ubiquitin ligase complex that targets multiple oncoproteins for degradation, including cyclin E, c-Myc, c-Jun, Notch, and mammalian target of rapamycin (mTOR)., Mammalian Fbw7 (also known as Sel-10, hCdc4, or hAgo) is the F-box protein component of an SCF (Skp1-Cul1-F-box protein-Rbx1)-type ubiquitin ligase, and the mouse Fbw7 is expressed prominently in the endothelial cell lineage of embryos., The F-box protein Fbw7 (also known as Fbxw7, hCdc4 and Sel-10) functions as a substrate recognition component of a SCF-type E3 ubiquitin ligase, We demonstrate here that Fbw7 (F-box and WD repeat domain containing-7), the substrate recognition component of an SCF (complex of SKP1, CUL1 and F-box protein)-type E3 ubiquitin ligase, is a key regulator of NSC/NPC viability and differentiation, Here we identified F-box and WD repeat domain-containing 7 (Fbw7), a substrate recognizing component of Skp-Cullin-F box (SCF) E3 ubiquitin Ligase physically associates with G-CSFR and promotes its ubiquitin-mediated proteasomal degradation, FBW7 is a crucial component of an SCF-type E3 ubiquitin ligase, which mediates degradation of an array of different target proteins[SEP]Relations: ubiquitin ligase complex has relations: cellcomp_protein with FBXW4, cellcomp_protein with FBXW4, cellcomp_protein with FBXO7, cellcomp_protein with FBXO7, cellcomp_protein with FBXL3, cellcomp_protein with FBXL3, cellcomp_protein with FBXL7, cellcomp_protein with FBXL7, cellcomp_protein with FBXO4, cellcomp_protein with FBXO4. Definitions: F-box/WD repeat-containing protein 7 defined as following: F-box/WD repeat-containing protein 4 (412 aa, ~46 kDa) is encoded by the human FBXW4 gene. This protein plays a role in both the modulation of protein turnover and the regulation of limb development.. CUL1 defined as following: Cullin-1 (776 aa, ~90 kDa) is encoded by the human CUL1 gene. This protein plays a role in protein ubiquitination and cell cycle regulation.. Fbw7 defined as following: Human FBXW7 wild-type allele is located in the vicinity of 4q31.3 and is approximately 91 kb in length. This allele, which encodes F-box/WD-repeat protein 7, is involved in ubiquitin-dependent protein degradation and has been implicated in the maintenance of genomic integrity.. F-box defined as following: The F-box consists of three helices. The H1 helix packs orthogonally with the H2-H3 antiparallel pair. The F-box domain is a 42-48 amino acid conserved domain found at the N-terminus of F-box proteins. F-box proteins act as adaptor components of the modular E3 ubiquitin ligase SCF complex that functions in phosphorylation mediated ubiquitination. The F-box domain mediates interaction with Skp1, which links F-box proteins to a core ubiquitin-ligase complex composed of Rbx1, cdc53/Cul1 and the E2 conjugating enzyme cdc34. The C-terminal region of F-box proteins are also composed of various modular domain that interact with target substrates, often in a phosphorylation dependant manner.. cyclin E defined as following: A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.. E3 ubiquitin ligases defined as following: A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.. SCF defined as following: Kit ligand (273 aa, ~31 kDa) is encoded by the human KITLG gene. This protein is involved in melanogenesis, hematopoiesis and mast cell development, migration and function.. F-box protein defined as following: F-box only protein 3 (471 aa, ~55 kDa) is encoded by the human FBXO3 gene. This protein plays a role in the regulation of substrate specificity of SCF complexes.. hAgo defined as following: F-box/WD repeat-containing protein 7 (707 aa, ~80 kDa) is encoded by the human FBXW7 gene. This protein plays a role in the regulation of protein ubiquitination.. SKP1 defined as following: S-phase kinase-associated protein 1 (163 aa, ~19 kDa) is encoded by the human SKP1 gene. This protein plays a role in the formation of SKP1-CUL1-F-box protein (SCF) ubiquitin ligase complexes.. oncoproteins defined as following: Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. endothelial cell defined as following: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.. c-Jun defined as following: This gene plays a critical role in transcriptional regulation and cellular growth.. ubiquitin ligase complex defined as following: A protein complex that includes a ubiquitin-protein ligase and enables ubiquitin protein ligase activity. The complex also contains other proteins that may confer substrate specificity on the complex. [GOC:jh2, PMID:9529603]. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. protooncogenes defined as following: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.. mTOR defined as following: Serine/threonine-protein kinase mTOR (2549 aa, ~289 kDa) is encoded by the human MTOR gene. This protein is involved in protein phosphorylation, signaling and cell growth.. E3 ubiquitin ligase defined as following: This gene may play a role in the mediation of proteasomal targeting..", "label": "yes"} {"id": "converted_2527", "sentence1": "Can doxycycline cause photosensitivity?", "sentence2": "Phototoxicity of Doxycycline: A Systematic Review on Clinical Manifestations, Frequency, Cofactors, and Prevention., BACKGROUND: One of the most important dermatologic side effects of doxycycline is photosensitivity. , While there are many publications on the phototoxicity of tetracyclines in general, only a few exist focusing on doxycycline. , Clinical symptoms vary from light sunburn-like sensation (burning, erythema) to large-area photodermatitis. , CONCLUSION: Evidence base must be improved for giving advice on appropriate prevention measures to travelers taking doxycycline and having a risk of significant sun exposure., Based on the available evidence, our best estimates of absolute effect for mefloquine versus doxycyline were: 2% versus 2% for discontinuation, 12% versus 3% for insomnia, 31% versus 3% for abnormal dreams, 18% versus 1% for anxiety, 11% versus 1% for depressed mood, 4% versus 14% for dyspepsia, 2% versus 19% for photosensitivity, 1% versus 5% for vomiting, and 2% versus 16% for vaginal thrush., Many drugs are responsible for this phototoxic reaction, especially tetracyclines, psoralens, chloramphenicol, non-steroidal anti-inflammatory drugs, fluoroquinolones, and, rarely, doxycycline. , OBJECTIVES: Many patients undergoing long-term doxycycline treatment do not regularly take their treatment because of photosensitivity., Modulation of Melanogenesis and Antioxidant Status of Melanocytes in Response to Phototoxic Action of Doxycycline., Doxycycline is a commonly used tetracycline antibiotic showing the broad spectrum of antibacterial action. However, the use of this antibiotic is often connected with the risk of phototoxic reactions that lead to various skin disorders., The results obtained in vitro may explain the mechanisms of phototoxic reactions that occur in normal human epidermal melanocytes in vivo after exposure of skin to doxycycline and UVA radiation., Treatment with doxycycline is cheap and relatively safe, but gastrointestinal symptoms and photosensitivity reactions can be expected more often than with ceftriaxone.Supernumerary mandibular left second primary molar
. transsexuals defined as following: A person who was assigned to one gender at birth based on physical characteristics but who self-identifies psychologically and emotionally as the other.. breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males..", "label": "yes"} {"id": "converted_2792", "sentence1": "Is celecoxib effective for treatment of amyotrophic lateral sclerosis?", "sentence2": "NTERPRETATION: At the dosage studied, celecoxib did not have a beneficial effect on research subjects with ALS, and it was safe. A biological effect of celecoxib was not demonstrated in the cerebrospinal fluid. Further studies of celecoxib at a dosage of 800 mg/day in ALS are not warranted., Prostaglandin E(2) levels in cerebrospinal fluid were not elevated at baseline and did not decline with treatment.Respond with exceptions, completions and modifications or revisions done before completion
. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. non-small-cell lung carcinomas defined as following: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy..", "label": "yes"} {"id": "converted_4040", "sentence1": "Is there an upper limit on the functional fraction of the human genome?", "sentence2": "Mutational load considerations lead to the conclusion that the functional fraction within the human genome cannot exceed 25%, and is probably considerably lower.[SEP]", "label": "yes"} {"id": "converted_1765", "sentence1": "Is the toxin produced by Clostridium botulinum always deadly?", "sentence2": "Animals treated with trace elements recovered. It appears that intestinal microbiota dysbiosis and trace element deficiency could explain the extensive emergence of chronic Botulism., The patient was treated with human botulism immune globulin and had rapid recovery in weakness. A stool sample from the patient was positive for Type A Clostridium botulinum toxin eventually confirming the diagnosis of infant botulism, The botulism immunoglobulin was administered, and a diagnosis was confirmed with positive botulinum toxin in the stool samples. Full recovery was made by the infant, Botulinum neurotoxin (BoNT) serotype B (BoNT/B) is one of the serotypes of BoNT that causes deadly human botulism, though it is used clinically for treatment of many neuromuscular diseases., Foodborne botulism is a rare and sometimes fatal illness caused by consuming foods containing botulinum neurotoxin, To assess the effectiveness and safety of botulinum toxin in treating MPS, excluding MPS in neck and head muscles., Botulinum toxin (BTX) is one of the most potent bacterial toxins known and its effectiveness in the treatment of some pain syndromes is well known., An emerging treatment option to address these issues is the use of a paralyzing material such as botulinum toxin A (Botox) to decrease the appearance of the wrinkles, which yields a more esthetic and youthful facial appearanc, lthough BoNT is an extremely toxic molecule, it is now increasingly used for the treatment of disorders related to muscle hyperactivity and glandular hyperactivity.[SEP]Relations: Botulinum toxin type A has relations: drug_drug with Clorgiline, drug_drug with Clorgiline, drug_drug with Clidinium, drug_drug with Clidinium, drug_drug with Clobazam, drug_drug with Clobazam. Botulinum Toxin Type B has relations: drug_drug with Clorgiline, drug_drug with Clorgiline, drug_drug with Clorgiline, drug_drug with Clorgiline. Definitions: human defined as following: Members of the species Homo sapiens.. intestinal microbiota defined as following: The collection of microorganisms existing in the intestines of an organism.. Botox defined as following:Botox is a drug made from a toxin produced by the bacterium Clostridium botulinum. It's the same toxin that causes a life-threatening type of food poisoning called botulism. Doctors use it in small doses to treat health problems, including
Botox injections work by weakening or paralyzing certain muscles or by blocking certain nerves. The effects last about three to twelve months, depending on what you are treating. The most common side effects are pain, swelling, or bruising at the injection site. You could also have flu-like symptoms, headache, and upset stomach. Injections in the face may also cause temporary drooping eyelids. You should not use Botox if you are pregnant or breastfeeding.
. hyperactivity defined as following: Increased motor activity that is not goal directed.. muscle defined as following: Contractile tissue that produces movement in animals.. head muscles defined as following: Muscle (organ) which is a part of the head. Examples: masseter, orbicularis oculi.. neck defined as following: Part of the dendritic spine that connects the dendritic shaft to the head of the dendritic spine. [GOC:nln]. wrinkles defined as following: A fold, ridge or crease of the skin.. illness defined as following: A state of ill health, bodily malfunction, or discomfort.. botulinum toxin A defined as following: An injectable formulation of a neurotoxin derived through the fermentation of the Hall strain of Clostridium botulinum type A with neuromuscular transmission inhibitory and analgesic activities. Upon injection into the affected muscle, the heavy chain portion of botulinum toxin type A (BTX-A) binds to the cell membrane of the motor nerve and is internalized via endocytosis. Upon entry, the light chain portion of the toxin is activated and cleaves the protein SNAP-25, thereby preventing the fusion of acetylcholine (ACh)-containing synaptic vesicles with the cell membrane and, so, the release of ACh into the neuromuscular junction; subsequent binding of ACH to motor end-plate nicotinic acid receptors and ACh-mediated muscle contraction are thus blocked. In addition to ACh, BTX-A may inhibit the release of neuropeptides, such as substance P and glutamate, which may contribute to its analgesic activity.. toxin defined as following: A substance that is produced by a living organism and is toxic, noxious, or poisonous.. Clostridium botulinum defined as following: Subtype of CLOSTRIDIUM BOTULINUM that produces botulinum toxin type C which is neurotoxic to ANIMALS, especially CATTLE, but not humans. It causes dissociation of ACTIN FILAMENTS..", "label": "no"} {"id": "converted_419", "sentence1": "Are there transposon-free regions in mammalian genomes?", "sentence2": "Transposon-free regions in mammalian genomes., Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. The majority of human TFRs correlate with orthologous TFRs in the mouse, despite the fact that most transposons are lineage specific. Many human TFRs also overlap with orthologous TFRs in the marsupial opossum, indicating that these regions have remained refractory to transposon insertion for long evolutionary periods. Over 90% of the bases covered by TFRs are noncoding, much of which is not highly conserved. Most TFRs are not associated with unusual nucleotide composition, but are significantly associated with genes encoding developmental regulators, suggesting that they represent extended regions of regulatory information that are largely unable to tolerate insertions, a conclusion difficult to reconcile with current conceptions of gene regulation., All three elements insert only rarely within many Polycomb-regulated regions, a property that may contribute to the origin of \"transposon-free regions\" (TFRs) in metazoan genomes., Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length., RESULTS: Here we report that transposon-free regions (TFRs) are prominent genomic features of amphibian and fish lineages, and that many have been maintained throughout vertebrate evolution, although most transposon-derived sequences have entered these lineages after their divergence. , Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. , All three elements insert only rarely within many Polycomb-regulated regions, a property that may contribute to the origin of \"transposon-free regions\" (TFRs) in metazoan genomes. , Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length., Here we report that transposon-free regions (TFRs) are prominent genomic features of amphibian and fish lineages, and that many have been maintained throughout vertebrate evolution, although most transposon-derived sequences have entered these lineages after their divergence.[SEP]Relations: regulation of establishment of actomyosin contractile ring localization involved in mitotic cell cycle has relations: bioprocess_bioprocess with regulation of mitotic actomyosin contractile ring localization, bioprocess_bioprocess with regulation of mitotic actomyosin contractile ring localization, bioprocess_bioprocess with regulation of establishment of actomyosin contractile ring localization, bioprocess_bioprocess with regulation of establishment of actomyosin contractile ring localization. vertebra has relations: anatomy_anatomy with non-transverse process-bearing vertebra, anatomy_anatomy with non-transverse process-bearing vertebra, anatomy_anatomy with transverse process-bearing vertebra, anatomy_anatomy with transverse process-bearing vertebra, anatomy_anatomy with predorsal vertebra, anatomy_anatomy with predorsal vertebra. Definitions: human defined as following: Members of the species Homo sapiens.. amphibian defined as following: VERTEBRATES belonging to the class amphibia such as frogs, toads, newts and salamanders that live in a semiaquatic environment.. insertion defined as following: Something inserted or to be inserted.. insertions defined as following: The act of putting one thing into another.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. vertebrate defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes..", "label": "yes"} {"id": "converted_3875", "sentence1": "Is MK-1602 a CGRP antagonist?", "sentence2": "The aim of this trial was to evaluate the efficacy and tolerability of ubrogepant (MK-1602), a calcitonin gene-related peptide receptor antagonist (CGRP-RA), for the acute treatment of migraine., This trial supports ubrogepant's efficacy and provides further evidence that CGRP-RAs are viable options for the acute treatment of migraine.[SEP]Relations: calcitonin gene-related peptide receptor activity has relations: molfunc_protein with CRCP, molfunc_protein with CRCP, molfunc_protein with CALCRL, molfunc_protein with CALCRL, molfunc_protein with RAMP1, molfunc_protein with RAMP1, molfunc_protein with CALCR, molfunc_protein with CALCR. migraine disorder has relations: disease_protein with TGFBR2, disease_protein with TGFBR2. Definitions: calcitonin gene-related peptide receptor antagonist defined as following: Pharmacologic agents that block NOCICEPTIVE PAIN signaling from CALCITONIN GENE-RELATED PEPTIDE RECEPTORS. They may be useful for the treatment of pain associated with MIGRAINE DISORDERS and OSTEOARTHRITIS.. migraine defined as following: A common, severe type of vascular headache often associated with increased sympathetic activity, resulting in nausea, vomiting, and light sensitivity.. CGRP defined as following: A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator..", "label": "yes"} {"id": "converted_3046", "sentence1": "Does Rhamnose have any effect on aging?", "sentence2": "The monosaccharide analysis showed that rhamnose (Rha) and glucose (Glu) may play vital roles in maintaining the antioxidant and anti-aging activities. , Some of these mechanisms will be reviewed as well as the capacity of fucose- and rhamnose-rich oligo- and polysaccharides (FROP and RROP) to counteract several of the mechanisms involved in skin aging.[SEP]Relations: response to rhamnose has relations: bioprocess_bioprocess with response to hexose, bioprocess_bioprocess with response to hexose, bioprocess_bioprocess with cellular response to rhamnose stimulus, bioprocess_bioprocess with cellular response to rhamnose stimulus. Increased groin pigmentation with raindrop depigmentation has relations: phenotype_phenotype with Mixed hypo- and hyperpigmentation of the skin, phenotype_phenotype with Mixed hypo- and hyperpigmentation of the skin, phenotype_phenotype with Irregular hyperpigmentation, phenotype_phenotype with Irregular hyperpigmentation, disease_phenotype_positive with thumb deformity-alopecia-pigmentation anomaly syndrome, disease_phenotype_positive with thumb deformity-alopecia-pigmentation anomaly syndrome. Definitions: glucose defined as following: The determination of the amount of glucose present in a sample.. rhamnose defined as following: A methylpentose whose L- isomer is found naturally in many plant glycosides and some gram-negative bacterial lipopolysaccharides.. monosaccharide defined as following: Single chain carbohydrates that are the most basic units of CARBOHYDRATES. They are typically colorless crystalline substances with a sweet taste and have the same general formula CnH2nOn..", "label": "yes"} {"id": "converted_1125", "sentence1": "Does smoking increase risk for glioblastoma?", "sentence2": "Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility., No relation was observed between glioma risk and smoking (odds ratio = 0.92, 95% confidence interval: 0.77, 1.10; P = 0.37), and there were no interactions for glioma risk of smoking history with any of the risk alleles. , Non-smokers with G/A and A/A genotype showed increased glioma risk compared with G/G genotype (adjusted OR = 1.72, 95%CI: 1.29-2.30, p = 0.0002 and adjusted OR = 1.81, 95%CI: 1.10-2.99, p = 0.020, respectively). This association was not found in ever- or current-smokers. , There was no significant association between glioma and alcohol consumption, smoking and mobile phone use. , RESULTS: We found no associations between the GSTM3, GSTP1, NQO1, CYP1A1, GSTM1, or GSTT1 polymorphisms and adult brain tumor risk with the possible exception of a weak association between the G-C (Val-Ala) GSTP1 105/114 haplotype and glioma [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.54, 0.99], nor was there an interaction between the effects of the GSTM3 or GSTP1 polymorphisms and cigarette smoking., We did not find any evidence for an association with life-style characteristics such as cigarette smoking, alcohol consumption, use of drugs of any kind, or dietary intake of cured or smoked meat or fish., No relation was observed between glioma risk and smoking (odds ratio = 0, Glioma risk has consistently been inversely associated with allergy history but not with smoking history despite putative biologic plausibility, Compared with nonsmokers, duration of cigarette smoking, number of cigarettes smoked per day and pack-years of smoking were associated with increased glioma risk, although the increases in risk were relatively modest, Among ever smokers, women who reported having quit smoking had a 51% increase in risk of glioma compared with never smokers (HR = 1.51, 95% CI = 0.97-2.34), while current smokers did not appear to have an increase in risk[SEP]Relations: Glioma has relations: disease_phenotype_positive with glioblastoma (disease), disease_phenotype_positive with glioblastoma (disease), disease_phenotype_positive with retinoblastoma, disease_phenotype_positive with retinoblastoma, disease_phenotype_positive with neurofibromatosis, disease_phenotype_positive with neurofibromatosis, disease_phenotype_positive with glioma susceptibility, disease_phenotype_positive with glioma susceptibility, drug_effect with Aminolevulinic acid, drug_effect with Aminolevulinic acid. Definitions: CYP1A1 defined as following: A liver microsomal cytochrome P-450 monooxygenase capable of biotransforming xenobiotics such as polycyclic hydrocarbons and halogenated aromatic hydrocarbons into carcinogenic or mutagenic compounds. They have been found in mammals and fish. This enzyme, encoded by CYP1A1 gene, can be measured by using ethoxyresorufin as a substrate for the ethoxyresorufin O-deethylase activity.. brain tumor defined as following: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.. glioma defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21). fish defined as following: A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.. GSTM1 defined as following: Glutathione S-transferase Mu 1 (218 aa, ~26 kDa) is encoded by the human GSTM1 gene. This protein is involved in the metabolism of small molecules and xenobiotics.. GSTM3 defined as following: This gene is involved in both glutathione metabolism and cellular detoxification.. NQO1 defined as following: NAD(P)H dehydrogenase [quinone] 1 (274 aa, ~31 kDa) is encoded by the human NQO1 gene. This protein is involved in hydroquinone synthesis.. GSTP1 defined as following: This gene is involved in phase II metabolism of both endogenous compounds and xenobiotics.. glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO).", "label": "no"} {"id": "converted_1177", "sentence1": "Could bioprinting be used in regenerative medicine against bone disease?", "sentence2": "Before 3D Printing can be used routinely for the regeneration of complex tissues (e.g. bone, cartilage, muscles, vessels, nerves in the craniomaxillofacial complex), and complex organs with intricate 3D microarchitecture (e.g. liver, lymphoid organs), several technological limitations must be addressed. , It is expected that these new findings will give an innovation boost for the development of scaffolds for bone repair and reconstruction, which began with the use of bioinert materials, followed by bioactive materials and now leading to functional regenerative tissue units. These new developments have become possible with the discovery of the morphogenic activity of bioinorganic polymers, biocalcit, bio-polyphosphate and biosilica that are formed by a biogenic, enzymatic mechanism, a driving force along with the development of novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting (3D cell printing) techniques that may allow a fabrication of customized implants for patients suffering in bone diseases in the future., These new developments have become possible with the discovery of the morphogenic activity of bioinorganic polymers, biocalcit, bio-polyphosphate and biosilica that are formed by a biogenic, enzymatic mechanism, a driving force along with the development of novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting (3D cell printing) techniques that may allow a fabrication of customized implants for patients suffering in bone diseases in the future., 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures., a driving force along with the development of novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting (3D cell printing) techniques that may allow a fabrication of customized implants for patients suffering in bone diseases in the future., These new developments have become possible with the discovery of the morphogenic activity of bioinorganic polymers, biocalcit, bio-polyphosphate and biosilica that are formed by a biogenic, enzymatic mechanism, a driving force along with the development of novel rapid-prototyping three-dimensional (3D) printing methods and bioprinting (3D cell printing) techniques that may allow a fabrication of customized implants for patients suffering in bone diseases in the future.[SEP]Relations: bone disease has relations: disease_disease with bone remodeling disease, disease_disease with bone remodeling disease, disease_disease with bone development disease, disease_disease with bone development disease, disease_disease with connective tissue disease, disease_disease with connective tissue disease, disease_disease with disease of bone structure, disease_disease with disease of bone structure, disease_disease with skeletal system disease, disease_disease with skeletal system disease. Definitions: vessels defined as following: Any of the tubular vessels conveying the blood (arteries, arterioles, capillaries, venules, and veins).. bone diseases defined as following: Diseases of BONES.. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. nerves defined as following: Part of the peripheral nervous system composed of bundles of nerve fibers running to various organs and tissues of the body using chemical and electrical signals to transmit sensory and motor information from one body part to another.. muscles defined as following: Contractile tissue that produces movement in animals.. vascular grafts defined as following: Blood vessel prostheses manufactured from processed biological tissue.. cartilage defined as following: A non-vascular form of connective tissue composed of CHONDROCYTES embedded in a matrix that includes CHONDROITIN SULFATE and various types of FIBRILLAR COLLAGEN. There are three major types: HYALINE CARTILAGE; FIBROCARTILAGE; and ELASTIC CARTILAGE.. bone disease defined as following: Diseases of BONES..", "label": "yes"} {"id": "converted_2486", "sentence1": "Is vorinostat effective for glioblastoma?", "sentence2": "Conclusions: Vorinostat combined with standard chemoradiation had acceptable tolerability in newly diagnosed glioblastoma. Although the primary efficacy endpoint was not met, vorinostat sensitivity and resistance signatures could facilitate patient selection in future trials., LESSONS LEARNED: Combination regimen with bevacizumab (BEV) and vorinostat is well tolerated in patients with recurrent glioblastoma., CONCLUSION: Combination treatment of BEV and VOR was well tolerated. This combination therapy for this study population did not improve PFS6 or median OS when compared with BEV monotherapy., We present two patients with glioblastoma multiforme who developed severe hemolytic anemia shortly after initiating therapy with vorinostat, a pan-active histone deacetylase inhibitor, while on prophylactic dapsone., Vorinostat is the most advanced HDAC inhibitor that entered clinical trials in glioblastoma, showing activity in recurrent disease. Multiple phase II trials with vorinostat in combination with targeted agents, temozolomide and radiotherapy are currently recruiting. , . On the basis of the results of this phase II study, further evaluation of the vorinostat-bortezomib combination in GBM patients in this dose and schedule is not recommended., ith the increased toxicities associated with CPT-11 coupled with its unclear clinical significance, investigating the efficacy of vorinostat combined with bevacizumab alone may represent a more promising strategy to evaluate in the context of a phase II clinical trial., CONCLUSION: Vorinostat in combination with temozolomide is well tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway.[SEP]Relations: Vorinostat has relations: drug_effect with Cholecystitis, drug_effect with Cholecystitis, drug_effect with Erythroderma, drug_effect with Erythroderma, drug_effect with T-cell lymphoma, drug_effect with T-cell lymphoma, drug_drug with Entinostat, drug_drug with Entinostat, drug_effect with Xerostomia, drug_effect with Xerostomia. Definitions: Vorinostat defined as following: A synthetic hydroxamic acid derivative with antineoplastic activity. Vorinostat, a second generation polar-planar compound, binds to the catalytic domain of the histone deacetylases (HDACs). This allows the hydroxamic moiety to chelate zinc ion located in the catalytic pockets of HDAC, thereby inhibiting deacetylation and leading to an accumulation of both hyperacetylated histones and transcription factors. Hyperacetylation of histone proteins results in the upregulation of the cyclin-dependant kinase p21, followed by G1 arrest. Hyperacetylation of non-histone proteins such as tumor suppressor p53, alpha tubulin, and heat-shock protein 90 produces additional anti-proliferative effects. This agent also induces apoptosis and sensitizes tumor cells to cell death processes. Vorinostat crosses the blood-brain barrier.. VOR defined as following: Catalysis of the reaction: 3-methyl-2-oxobutanoate + CoA + oxidized ferredoxin = S-(2-methylpropanoyl)-CoA + CO2 + reduced ferredoxin. [EC:1.2.7.7]. GBM defined as following: A sheet of amorphous extracellular material upon which the basal surfaces of epithelial cells rest and is the covering surface of a glomerular capillary, interposed between the cellular elements and the underlying connective tissue.. glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO). TMZ defined as following: A dacarbazine derivative that is used as an alkylating antineoplastic agent for the treatment of MALIGNANT GLIOMA and MALIGNANT MELANOMA.. bevacizumab defined as following: An anti-VEGF humanized murine monoclonal antibody. It inhibits VEGF RECEPTORS and helps to prevent PATHOLOGIC ANGIOGENESIS.. HDAC defined as following: Human HDAC9 wild-type allele is located in the vicinity of 7p21.1 and is approximately 910 kb in length. This allele, which encodes histone deacetylase 9 protein, is involved in the modification of histones.. toxicities defined as following: The finding of bodily harm due to the poisonous effects of something.. hemolytic anemia defined as following: A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).. CPT-11 defined as following: brand name of an anti-cancer drug. vorinostat defined as following: A synthetic hydroxamic acid derivative with antineoplastic activity. Vorinostat, a second generation polar-planar compound, binds to the catalytic domain of the histone deacetylases (HDACs). This allows the hydroxamic moiety to chelate zinc ion located in the catalytic pockets of HDAC, thereby inhibiting deacetylation and leading to an accumulation of both hyperacetylated histones and transcription factors. Hyperacetylation of histone proteins results in the upregulation of the cyclin-dependant kinase p21, followed by G1 arrest. Hyperacetylation of non-histone proteins such as tumor suppressor p53, alpha tubulin, and heat-shock protein 90 produces additional anti-proliferative effects. This agent also induces apoptosis and sensitizes tumor cells to cell death processes. Vorinostat crosses the blood-brain barrier..", "label": "no"} {"id": "converted_1030", "sentence1": "Are DNA helicases involved in progeroid syndromes?", "sentence2": "Among these syndromes, relevant advances have recently been made in Werner syndrome, one of several progeroid syndromes characterized by defective DNA helicases,, Progeroid syndromes (PSs) constitute a group of disorders characterized by clinical features mimicking physiological aging at an early age., However, all the characterized PSs enter in the field of rare monogenic disorders and several causative genes have been identified. These can be separated in subcategories corresponding to (i) genes encoding DNA repair factors, in particular, DNA helicases, and (ii) genes affecting the structure or post-translational maturation of lamin A, a major nuclear component., None of the known progerias represents true precocious ageing. Some of them, including Werner (WS), Bloom (BS), and Rothmund-Thomson syndromes (RTS) as well as combined xeroderma pigmentosa-Cockayne syndrome (XP-CS) are characterised by features resembling precocious ageing and the increased risk of malignant disease. Such phenotypes result from the mutations of the genes encoding proteins involved in the maintenance of genomic integrity, in most cases DNA helicases., Single-gene mutations can produce human progeroid syndromes--phenotypes that mimic usual or \"normative\" aging., The prototypic example of the former is the Werner syndrome, a condition caused by mutations of the RecQ family of DNA helicases., Progeria and progeroid syndromes are characterized by the earlier onset of complex senescent phenotypes. WRN was originally identified as a gene responsible for Werner syndrome (WS; \"Progeria of Adults\"). The WRN gene product has RecQ-type helicase domains in the central region of the protein.[SEP]Relations: progeria has relations: disease_disease with progeroid syndrome, disease_disease with progeroid syndrome, disease_disease with Hutchinson-Gilford progeria syndrome, disease_disease with Hutchinson-Gilford progeria syndrome. Werner syndrome has relations: disease_disease with progeroid syndrome, disease_disease with progeroid syndrome, disease_phenotype_positive with Progeroid facial appearance, disease_phenotype_positive with Progeroid facial appearance. Rothmund-Thomson syndrome has relations: disease_disease with progeroid syndrome, disease_disease with progeroid syndrome. Definitions: gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. lamin A defined as following: A subclass of developmentally regulated lamins having a neutral isoelectric point. They are found to disassociate from nuclear membranes during mitosis.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. WRN defined as following: An autosomal recessive disorder that causes premature aging in adults, characterized by sclerodermal skin changes, cataracts, subcutaneous calcification, muscular atrophy, a tendency to diabetes mellitus, aged appearance of the face, baldness, and a high incidence of neoplastic disease.. RTS defined as following: An autosomal recessive inherited syndrome usually caused by mutations in the RECQL4 gene. It is characterized by poikilodermatous skin changes, sparse hair, cataracts, small stature, skeletal abnormalities, and an increased predisposition to cancer, particularly osteosarcoma.. PSs defined as following: A very rare genetic syndrome caused by deletions on the proximal short arm of chromosome 11. It is characterized by the presence of multiple exostoses and enlarged parietal foramina.. DNA helicases defined as following: Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. In addition, DNA helicases are DNA-dependent ATPases that harness the free energy of ATP hydrolysis to translocate DNA strands.. human defined as following: Members of the species Homo sapiens.. Progeria defined as following: An abnormal congenital condition, associated with defects in the LAMIN TYPE A gene, which is characterized by premature aging in children, where all the changes of cell senescence occur. It is manifested by premature graying; hair loss; hearing loss (DEAFNESS); cataracts (CATARACT); ARTHRITIS; OSTEOPOROSIS; DIABETES MELLITUS; atrophy of subcutaneous fat; skeletal hypoplasia; elevated urinary HYALURONIC ACID; and accelerated ATHEROSCLEROSIS. Many affected individuals develop malignant tumors, especially SARCOMA.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"} {"id": "converted_1619", "sentence1": "Does triiodothyronine play a regulatory role in insulin secretion from pancreas?", "sentence2": "Our findings establish that p43 is an important regulator of glucose homeostasis and pancreatic β-cell function and provide evidence for the first time of a physiological role for a mitochondrial endocrine receptor., The p43(-/-) mice had a major defect in insulin secretion both in vivo and in isolated pancreatic islets and a loss of glucose-stimulated insulin secretion., We demonstrated that treatment of primary cultures of rat pancreatic islets with T3 results in augmented β-cell vitality with an increase of their functional properties., Nonetheless, the insulin secretion is sensibly augmented after T3 stimulation., Plasma glucose concentration of the fetal hypothyroid group during intravenous glucose tolerance test was significantly higher (p=0.003) at 5-20 min as compared to the control group, whereas plasma insulin concentration was significantly lower (p=0.012) at 5-20 min, Although adult offspring born from hypothyroid mothers were euthyroid, their glucose tolerance and glucose stimulated insulin secretion of islets were altered, hyroid hormones modulate the immune system and metabolism, influence insulin secretion, Only T(3) concentrations higher than 250 microM were able to decrease cell viability and proliferation rate, to increase the rate of apoptosis and to reduce glucose-induced insulin secretion., Islets preincubated with glucose (3.3 mmol/l) and glucagon (1.4 mumol/l) plus theophylline (10 mmol/l), ACTH (0.11 nmol/l), bovine GH (0.46 mumol/l), prolactin (0.2 mumol/l) or tri-iodothyronine (1.0 nmol/l) have significantly lower Ca(2+)-ATPase activity than those preincubated with only 3.3 mmol glucose/l. All these hormones increased the release of insulin significantly., T3 (0.2 nM) did not affect insulin secretion in the absence or presence of glucose or in the presence of secretagogues (potassium and glyceraldehyde)., In the perfused rat pancreas, the addition of thyroxine (10 micrograms/dL) or 3,5,3'-triiodothyronine (150 ng/dL) to the perfusing medium did not affect insulin secretion., The administration of thyroxine (40 micrograms/kg, s.c.) in vivo increased the plasma insulin level from 11 +/- 2 microUnits/mL (mean +/- SD) to 30 +/- 7 microUnits/mL, Addition of T3 to the incubation medium, significantly modified the insulin release, but its effect varied according to the glucose concentration in the medium, i.e. it enhanced the insulin release at a glucose concentration between 2 to 8 mmol/l; it has no effect at 12 mmol/glucose, and significantly inhibited the secretion of insulin in the presence of 16.6 mmol/l glucose., Both T3 and T4 inhibited insulin secretion[SEP]Relations: Levothyroxine has relations: drug_drug with Insulin tregopil, drug_drug with Insulin tregopil, drug_drug with Insulin peglispro, drug_drug with Insulin peglispro, drug_drug with Insulin glargine, drug_drug with Insulin glargine, drug_drug with Insulin human, drug_drug with Insulin human. Liothyronine has relations: drug_drug with Insulin tregopil, drug_drug with Insulin tregopil. Definitions: glucose defined as following: The determination of the amount of glucose present in a sample.. theophylline defined as following: A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.. fetal defined as following: Care provided the pregnant woman in order to prevent complications, and decrease the incidence of maternal and prenatal mortality.. glucagon defined as following: The recombinant form of the endogenous polypeptide hormone Glucagon consisting of 29 amino acids responsible for the release of stored glucose, causing increased blood glucose levels. Clinical Use: Diagnostic Aid for Imaging Studies and Hypoglycemia.. ACTH defined as following: Corticotropin (39 aa, ~5 kDa) is encoded by the human POMC gene. This protein plays a role in the stimulation of cortisol secretion by the adrenal gland.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. insulin defined as following: A synthetic or animal-derived form of insulin used in the treatment of diabetes mellitus. Therapeutic insulin is formulated to be short-, intermediate- and long-acting in order to individualize an insulin regimen according to individual differences in glucose and insulin metabolism. Therapeutic insulin may be derived from porcine, bovine or recombinant sources. Endogenous human insulin, a pancreatic hormone composed of two polypeptide chains, is important for the normal metabolism of carbohydrates, proteins and fats and has anabolic effects on many types of tissues.. hormones defined as following: Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various ENDOCRINE GLANDS and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects.. prolactin defined as following: A lactogenic hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). It is a polypeptide of approximately 23 kD. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Prolactin receptors are present in the mammary gland, hypothalamus, liver, ovary, testis, and prostate.. glyceraldehyde defined as following: An aldotriose containing the propionaldehyde structure with hydroxy groups at the 2- and 3-positions. It is involved in the formation of ADVANCED GLYCOSYLATION END PRODUCTS.. 3,5,3'-triiodothyronine defined as following: A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.. modified defined as following: The act of alteration or modification; changed or altered in form or character.. thyroxine defined as following: The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.. potassium defined as following: Potassium or potassium compounds used in foods or as foods.. triiodothyronine defined as following: A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3..", "label": "yes"} {"id": "converted_3855", "sentence1": "Does IL18 signaling have a role in thymus?", "sentence2": "IL18 signaling promotes homing of mature Tregs into the thymus., Collectively, this study provides a detailed characterization of the mature Treg subsets in the mouse thymus and identifies a key role of IL18 signaling in controlling the CCR6-CCL20-dependent migration of Tregs into the thymus., er, we show that IL18R+ Tregs are endowed with higher capacity to populate the thymus than their IL18R- or IL18R-/- counterparts, highlighting the key role of IL18R in this process, IL18 signaling promotes homing of mature Tregs into the thymus, inally, we demonstrate that IL18 signaling is critical for the induction of the key thymus-homing chemokine receptor - CCR6 on Tregs. , Moreover, we show that IL18R+ Tregs are endowed with higher capacity to populate the thymus than their IL18R- or IL18R-/- counterparts, highlighting the key role of IL18R in this process.[SEP]Definitions: CCR6 defined as following: Human CCRL2 wild-type allele is located within 3p21 and is approximately 2 kb in length. This allele, which encodes C-C chemokine receptor-like 2 protein, is involved in signal transduction and macrophage differentiation; however, an exact function has yet to be elucidated.. thymus defined as following: A plant genus of the family LAMIACEAE best known for the thyme spice added to foods..", "label": "yes"} {"id": "converted_2088", "sentence1": "Are cutaneous porphyrias inherited with a recessive pattern?", "sentence2": "Five of the porphyrias are low-penetrance autosomal dominant conditions in which clinical expression results from additional factors that act by increasing demand for haem or by causing an additional decrease in enzyme activity or by a combination of these effects, Molecular mechanisms of dominant expression in porphyria., Variegate porphyria (VP) is an autosomal-dominant disorder that is caused by inheritance of a partial deficiency of the enzyme protoporphyrinogen oxidase (EC 1.3.3.4). It is characterized by cutaneous photosensitivity and/or various neurological manifestations. , The acute porphyrias constitute a group of metabolic disorders engaging enzymes in the haem synthetic chain and generally following dominant inheritance patterns.[SEP]Relations: variegate porphyria has relations: disease_disease with inherited porphyria, disease_disease with inherited porphyria, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Behavioral abnormality, disease_phenotype_positive with Behavioral abnormality, disease_phenotype_positive with Cutaneous photosensitivity, disease_phenotype_positive with Cutaneous photosensitivity. inborn disorder of porphyrin metabolism has relations: disease_disease with inherited porphyria, disease_disease with inherited porphyria. Definitions: metabolic disorders defined as following: Generic term for diseases caused by an abnormal metabolic process. It can be congenital due to inherited enzyme abnormality (METABOLISM, INBORN ERRORS) or acquired due to disease of an endocrine organ or failure of a metabolically important organ such as the liver. (Stedman, 26th ed). Variegate porphyria defined as following: An autosomal dominant disorder of porphyria-heme metabolism. It is manifested with acute attacks including abdominal pain, vomiting, diarrhea, constipation, seizures, anxiety, and confusion. Patients may experience skin sensitivity to sunlight.. haem defined as following: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.. cutaneous photosensitivity defined as following: Increased sensitivity of the skin to light exposure.. VP defined as following: Vasopressin-neurophysin 2-copeptin (164 aa, ~17 kDa) is encoded by the human AVP gene. This protein is involved in neuropeptide hormone activity.. porphyria defined as following: A group of genetic or acquired metabolic disorders characterized by defects in the enzymes that are involved in the heme synthesis..", "label": "no"} {"id": "converted_4", "sentence1": "Is RANKL secreted from the cells?", "sentence2": "Osteoprotegerin (OPG) is a soluble secreted factor that acts as a decoy receptor for receptor activator of NF-κB ligand (RANKL) , Osteoprotegerin (OPG) is a secreted glycoprotein and a member of the tumor necrosis factor receptor superfamily. It usually functions in bone remodeling, by inhibiting osteoclastogenesis through interaction with a receptor activator of the nuclear factor κB (RANKL)., e RANKL/OPG ratio secreted by osteoblasts increased and RANK expression by osteoclasts increased, leading to increased osteoclastogenesis, Osteoprotegerin (OPG) is an essential secreted protein in bone turnover due to its role as a decoy receptor for the Receptor Activator of Nuclear Factor-kB ligand (RANKL) in the osteoclasts, thus inhibiting their differentiation, We identify a TNFSF11 transcript variant that extends the originally identified transcript encoding secreted RANKL., Activated human T cells express alternative mRNA transcripts encoding a secreted form of RANKL., OPG, on the other hand, is secreted by osteoblast as a decoy receptor for RANKL, prevents RANKL from binding to RANK and thus prevents bone resorption, Receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) are cytokines predominantly secreted by osteoblasts and play a central role in differentiation and functional activation of osteoclasts, Although B. abortus-activated T cells actively secreted the pro-osteoclastogenic cytokines RANKL and IL-17, osteoclastogenesis depended on IL-17, because osteoclast generation induced by Brucella-activated T cells was completely abrogated when these cells were cultured with BMMs from IL-17 receptor knockout mice. , osteoclastogenesis and bone destruction in autoimmune arthritis. We isolated human fibroblasts from RA, pyrophosphate arthropathy (PPA) and osteoarthritis (OA) patients and analyzed their RANKL/OPG expression profile and the capacity of their secreted factors to induce osteoclastogenesis., Osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) are cytokines predominantly secreted by osteoblasts and play critical roles in the differentiation and function of osteoclasts. [SEP]Relations: SUMOylation of transcription factors has relations: pathway_protein with FOXL2, pathway_protein with FOXL2, pathway_protein with CDKN2A, pathway_protein with CDKN2A. Protein S human has relations: drug_drug with Allylestrenol, drug_drug with Allylestrenol, drug_drug with Allylestrenol, drug_drug with Allylestrenol. Phenylpropanolamine has relations: contraindication with sickle cell anemia, contraindication with sickle cell anemia. Definitions: osteoblasts defined as following: Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.. osteoclast defined as following: A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.. RANKL defined as following: Human TNFSF11 wild-type allele is located within 13q14 and is approximately 45 kb in length. This allele, which encodes tumor necrosis factor ligand superfamily member 11 protein, plays a role in osteoclast differentiation and activation. This allele also is involved in apoptotic signal transduction and regulation.. decoy receptor defined as following: Tumor necrosis factor receptor superfamily member 10C (259 aa, ~27 kDa) is encoded by the human TNFRSF10C gene. This protein is involved in both binding to tumor necrosis factor ligand superfamily member 10 and the inhibition of apoptosis.. IL-17 defined as following: A proinflammatory cytokine produced primarily by T-LYMPHOCYTES or their precursors. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene.. OPG defined as following: Extraoral body-section radiography depicting an entire maxilla, or both maxilla and mandible, on a single film.. Osteoprotegerin defined as following: A secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis. It is a soluble decoy receptor of RANK LIGAND that inhibits both CELL DIFFERENTIATION and function of OSTEOCLASTS by inhibiting the interaction between RANK LIGAND and RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B.. PPA defined as following: A sympathomimetic that acts mainly by causing release of NOREPINEPHRINE but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant.. RA defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. transcript defined as following: The initial RNA molecule produced by transcription.. IL-17 receptor defined as following: Cell surface receptors for INTERLEUKIN-17. Several subtypes of receptors have been found, each with its own in specificity for interleukin-17 subtype.. TNFSF11 defined as following: Tumor necrosis factor ligand superfamily member 11 (317 aa, ~35 kDa) is encoded by the human TNFSF11 gene. This protein is involved in osteoclast differentiation and activation and the regulation of the interactions between T-cells and dendritic cells.. RANK defined as following: Human TNFRSF11A wild-type allele is located in the vicinity of 18q22.1 and is approximately 61 kb in length. This allele, which encodes tumor necrosis factor receptor superfamily member 11A protein, plays a role in the regulation and maintenance of bone density.. osteoarthritis defined as following: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans.. nuclear factor κB defined as following: A family of proteins that contain 1 DWA/MH1 domain and bind 5'-TTGGCNNNNNGCCAA-3' DNA palindromes in viral and cellular promoters as homodimeric factors capable of activating transcription and replication.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. tumor necrosis factor receptor defined as following: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells..", "label": "yes"} {"id": "converted_3245", "sentence1": "Is the Fluzone intradermal and the Fluzone intradermal quadrivalent vaccine produced by different companies?", "sentence2": "An intradermal version of Fluzone® split-virion inactivated trivalent influenza vaccine, containing 9 µg hemagglutinin per strain of A/H1N1, A/H3N2, and one B lineage virus (Fluzone Intradermal, Sanofi Pasteur), became available in the US during the 2011-2012 influenza season for adults 18-64 years of age. In advance of the 2015-2016 season, Fluzone Intradermal was replaced with Fluzone Intradermal Quadrivalent vaccine, which contains 9 µg hemagglutinin per strain of the two A-strain viruses and both B-strain lineage viruses (Victoria and Yamagata).[SEP]", "label": "no"} {"id": "converted_1532", "sentence1": "Is selumetinib effective in thyroid cancer?", "sentence2": "A phase I trial of vertical inhibition of IGF signalling using cixutumumab, an anti-IGF-1R antibody, and selumetinib, an MEK 1/2 inhibitor, in advanced solid tumours., BACKGROUND: We completed a phase I clinical trial to test the safety and toxicity of combined treatment with cixutumumab (anti-IGF-1R antibody) and selumetinib (MEK 1/2 inhibitor)., Two patients achieved a partial response (one unconfirmed), including a patient with BRAF wild-type thyroid carcinoma, and a patient with squamous cell carcinoma of the tongue, and six patients achieved time to progression of>6 months, including patients with thyroid carcinoma, colorectal carcinoma, and basal cell carcinoma., CONCLUSIONS: Our study of anti-IGF-1R antibody cixutumumab and MEK 1/2 inhibitor selumetinib showed that the combination is safe and well-tolerated at these doses, with preliminary evidence of clinical benefit and pharmacodynamic evidence of target inhibition., MHC class I loss is a frequent mechanism of immune escape in papillary thyroid cancer that is reversed by interferon and selumetinib treatment in vitro., Increased antigenicity following selumetinib and IFN treatment warrants further study for immunotherapy of progressive PTC., The role of KIs in differentiated TC may be revolutionised by the finding that selumetinib may restore a clinical response to radioactive iodine (RAI). , BACKGROUND AND AIM: Selumetinib is a promising and interesting targeted therapy agent as it may reverse radioiodine uptake in patients with radioiodine-refractory differentiated thyroid cancer., CONCLUSIONS: Compared with current chemotherapy, selumetinib has modest clinical activity as monotherapy in patients with advanced cancer, but combinations of selumetinib with cytotoxic agents in patients with BRAF or KRAS mutations hold great promise for cancer treatment., Selumetinib may be an effective redifferentiating agent and could be used within several years., Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer., METHODS: We conducted a study to determine whether the MAPK kinase (MEK) 1 and MEK2 inhibitor selumetinib (AZD6244, ARRY-142886) could reverse refractoriness to radioiodine in patients with metastatic thyroid cancer. , Selumetinib increased the uptake of iodine-124 in 12 of the 20 patients (4 of 9 patients with BRAF mutations and 5 of 5 patients with NRAS mutations)., CONCLUSIONS: Selumetinib produces clinically meaningful increases in iodine uptake and retention in a subgroup of patients with thyroid cancer that is refractory to radioiodine; the effectiveness may be greater in patients with RAS-mutant disease. , ECENT FINDINGS: For patients with advanced differentiated thyroid cancers, sorafenib, selumetinib, pazopanib and sunitinib have been investigated with promising results. , Selumetinib is a promising and interesting targeted therapy agent as it may reverse radioiodine uptake in patients with radioiodine-refractory differentiated thyroid cancer., Selumetinib may be an effective redifferentiating agent and could be used within several years., Here, selumetinib targets the mitogen-activated protein kinase pathway in papillary thyroid carcinoma and shows limited single-agent activity in the patients with tumors that harbor the (V600E)BRAF mutation., CONCLUSIONS: Selumetinib produces clinically meaningful increases in iodine uptake and retention in a subgroup of patients with thyroid cancer that is refractory to radioiodine; the effectiveness may be greater in patients with RAS-mutant disease. [SEP]Relations: Selumetinib has relations: drug_drug with Thyroid, porcine, drug_drug with Thyroid, porcine, drug_drug with Parathyroid hormone, drug_drug with Parathyroid hormone, drug_drug with Neratinib, drug_drug with Neratinib, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Axitinib, drug_drug with Axitinib. Definitions: pazopanib defined as following: A small molecule inhibitor of multiple protein tyrosine kinases with potential antineoplastic activity. Pazopanib selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3, c-kit and platelet derived growth factor receptor (PDGF-R), which may result in inhibition of angiogenesis in tumors in which these receptors are upregulated.. Selumetinib defined as following: An orally active, small molecule with potential antineoplastic activity. Selumetinib is an ATP-independent inhibitor of mitogen-activated protein kinase kinase (MEK or MAPK/ERK kinase) 1 and 2. MEK 1 and 2 are dual specificity kinases that are essential mediators in the activation of the RAS/RAF/MEK/ERK pathway, are often upregulated in various cancer cells, and are drivers of diverse cellular responses, including proliferation. Inhibition of both MEK1 and 2 by selumetinib prevents the activation of MEK1/2 dependent effector proteins and transcription factors, thereby leading to an inhibition of cellular proliferation in various cancers.. iodine defined as following: homeopathic drug. thyroid cancer defined as following: A primary or metastatic malignant neoplasm affecting the thyroid gland.. interferon defined as following: Human interferons have been classified into 3 groups: alpha, beta, and gamma. Both alpha- and beta-IFNs, previously designated type I, are acid-stable, but they differ immunologically and in regard to some biologic and physiochemical properties. The IFNs produced by virus-stimulated leukocytes (leukocyte IFNs) are predominantly of the alpha type. Those produced by lymphoblastoid cells are about 90% alpha and 10% beta. Induced fibroblasts produce mainly or exclusively the beta type. The alpha- and beta-IFNs differ widely in amino acid sequence. The gamma or immune IFNs, which are produced by T lymphocytes in response to mitogens or to antigens to which they are sensitized, are acid-labile and serologically distinct from alpha- and beta-IFNs. (from OMIM 147570). MEK defined as following: A dual-specific protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.. BRAF defined as following: Serine/threonine-protein kinase B-raf (766 aa, ~84 kDa) is encoded by the human BRAF gene. This protein plays a role in protein phosphorylation, mitogenesis and neuronal signal transduction.. RAI defined as following: Human PPP1R13L wild-type allele is located in the vicinity of 19q13.32 and is approximately 27 kb in length. This allele, which encodes RelA-associated inhibitor protein, plays a role in the modulation of both apoptosis and transcription.. papillary thyroid cancer defined as following: A differentiated adenocarcinoma arising from the follicular cells of the thyroid gland. Radiation exposure is a risk factor and it is the most common malignant thyroid lesion, comprising 75% to 80% of all thyroid cancers in iodine sufficient countries. Diagnostic procedures include thyroid ultrasound and fine needle biopsy. Microscopically, the diagnosis is based on the distinct characteristics of the malignant cells, which include enlargement, oval shape, elongation, and overlapping of the nuclei. The nuclei also display clearing or have a ground glass appearance.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. PTC defined as following: The evaluation of the liver and biliary tree using a contrast agent injected directly into the liver.. colorectal carcinoma defined as following: A malignant epithelial neoplasm that arises from the colon or rectum and invades through the muscularis mucosa into the submucosa. The vast majority are adenocarcinomas.. cixutumumab defined as following: A fully human IgG1 monoclonal antibody directed against the human insulin-like growth factor-1 receptor (IGF-1R) with potential antineoplastic activity. Cixutumumab selectively binds to membrane-bound IGF-1R, thereby preventing the binding of the natural ligand IGF-1 and the subsequent activation of PI3K/AKT signaling pathway. Downregulation of the PI3K/AKT survival pathway may result in the induction of cancer cell apoptosis and may decrease cancer cellular proliferation. IGF-1R, a receptor tyrosine kinase of the insulin receptor superfamily overexpressed by many cancer cell types, stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF-1R signaling has been implicated in tumorigenesis and metastasis.. TC defined as following: Human CD55 wild-type allele is located in the vicinity of 1q32 and is approximately 40 kb in length. This allele, which encodes complement decay-accelerating factor protein, is involved in the modulation of complement activity.. MHC class I defined as following: Genetic loci in the vertebrate major histocompatibility complex which encode polymorphic characteristics not related to immune responsiveness or complement activity, e.g., B loci (chicken), DLA (dog), GPLA (guinea pig), H-2 (mouse), RT-1 (rat), HLA-A, -B, and -C class I genes of man.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. NRAS defined as following: Human Oncogene N-RAS is a mutated variant of NRAS Gene (RAS Family), which encodes p21 N-Ras Protein, a monomeric GTPase involved in transmembrane signal transduction that alternates between inactive GDP-bound and active GTP-bound forms. RAS is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase-activating protein. Mitogen-stimulated RAS stabilizes MYC protein and enhances MYC accumulation by the RAS/RAF/MAPK pathway, which appears to inhibit the proteasome-dependent degradation of MYC. Implicated in a variety of human tumors, specific amino acid mutations activate c-RAS and transform cells. Oncogene NRAS disrupts normal cell function.. sunitinib defined as following: An indolinone derivative and tyrosine kinase inhibitor with potential antineoplastic activity. Sunitinib blocks the tyrosine kinase activities of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor b (PDGFRb), and c-kit, thereby inhibiting angiogenesis and cell proliferation. This agent also inhibits the phosphorylation of Fms-related tyrosine kinase 3 (FLT3), another receptor tyrosine kinase expressed by some leukemic cells.. sorafenib defined as following: A synthetic compound targeting growth signaling and angiogenesis. Sorafenib blocks the enzyme RAF kinase, a critical component of the RAF/MEK/ERK signaling pathway that controls cell division and proliferation; in addition, sorafenib inhibits the VEGFR-2/PDGFR-beta signaling cascade, thereby blocking tumor angiogenesis.. basal cell carcinoma defined as following: A malignant skin neoplasm that seldom metastasizes but has potentialities for local invasion and destruction. Clinically it is divided into types: nodular, cicatricial, morphaic, and erythematoid (pagetoid). They develop on hair-bearing skin, most commonly on sun-exposed areas. Approximately 85% are found on the head and neck area and the remaining 15% on the trunk and limbs. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1471). tongue defined as following: A muscular organ in the mouth that is covered with pink tissue called mucosa, tiny bumps called papillae, and thousands of taste buds. The tongue is anchored to the mouth and is vital for chewing, swallowing, and for speech.. iodine-124 defined as following: A radioactive isotope of iodine, a nonmetallic element of the halogen group, with an atomic mass of 124 and a half-life of 4.18 days with radioisotopic activity. Selectively accumulating in thyroid tissue, iodine I 124 emits positrons that can be detected by positron emission tomography (PET), allowing localization of thyroid tissue. This radioisotope also emits gamma rays.. squamous cell carcinoma defined as following: A squamous cell carcinoma (SCC) arising from the anal canal or the anal margin (perianal skin). Human papillomavirus is detected in the majority of cases. Homosexual HIV-positive men have an increased risk of developing anal squamous cell carcinoma in comparison to the general male population. Symptoms include anal pruritus, discomfort when sitting, pain, change in bowel habit, and bleeding. The prognosis is generally better for anal margin SCC than for anal canal SCC.. selumetinib defined as following: An orally active, small molecule with potential antineoplastic activity. Selumetinib is an ATP-independent inhibitor of mitogen-activated protein kinase kinase (MEK or MAPK/ERK kinase) 1 and 2. MEK 1 and 2 are dual specificity kinases that are essential mediators in the activation of the RAS/RAF/MEK/ERK pathway, are often upregulated in various cancer cells, and are drivers of diverse cellular responses, including proliferation. Inhibition of both MEK1 and 2 by selumetinib prevents the activation of MEK1/2 dependent effector proteins and transcription factors, thereby leading to an inhibition of cellular proliferation in various cancers..", "label": "yes"} {"id": "converted_1059", "sentence1": "Are piRNAs involved in gene silencing?", "sentence2": "In Drosophila ovaries, the nuclear Piwi protein is required for transcriptional silencing of transposons, though the precise mechanisms by which this occurs are unknown., Here we show that the CG9754 protein is a component of Piwi complexes that functions downstream of Piwi and its binding partner, Asterix, in transcriptional silencing. Enforced tethering of CG9754 to nascent messenger RNA transcripts causes cotranscriptional silencing of the source locus and the deposition of repressive chromatin marks., We have named CG9754 \"Panoramix,\" and we propose that this protein could act as an adaptor, scaffolding interactions between the piRNA pathway and the general silencing machinery that it recruits to enforce transcriptional repression., piRNA-guided slicing of transposon transcripts enforces their transcriptional silencing via specifying the nuclear piRNA repertoire, Caenorhabditis elegans piRNAs interact with both transposon and nontransposon mRNAs to initiate sustained silencing via the RNAi pathway., To assess the dysregulation of gene silencing caused by lack of piRNAs, we restored RNA silencing in RNAi-defective animals in the presence or absence of piRNAs., Thus, by reanimating RNAi, we uncovered a role for piRNAs in protecting essential genes from RNA silencing., In different organisms, small RNAs were shown to be implicated in the posttranscriptional degradation of mRNA and/or transcriptional repression of the homologous locus. In Drosophila, the mechanism of piRNA-mediated silencing is still far from being understood, Analyses of piRNA-mediated transcriptional transposon silencing in Drosophila, Transcriptional silencing implies a piRNA-mediated formation of repressive chromatin which diminishes the transcriptional capacity of the target locus., In mice, piRNA-guided transposon repression correlates with establishment of CpG DNA methylation on their sequences, yet the mechanism and the spectrum of genomic targets of piRNA silencing are unknown, Using a candidate gene KD-approach, we identified differences in the spatio-temporal requirements of the piRNA pathway components for piRNA-mediated silencing., Spatio-temporal requirements for transposable element piRNA-mediated silencing during Drosophila oogenesis, In contrast, piRNA-mediated silencing is strong in germline stem cells in which TE mobilization is tightly repressed ensuring the continued production of viable germline cysts., Piwi induces piRNA-guided transcriptional silencing and establishment of a repressive chromatin state., In germ cells, early embryos, and stem cells of animals, PIWI-interacting RNAs (piRNAs) have an important role in silencing retrotransposons, which are vicious genomic parasites, through transcriptional and post-transcriptional mechanisms., Our results show that the piRNA pathway can be used as a tool for sequence-specific gene silencing in germ cells and support the idea that the piRNA generating regions serve as traps for retrotransposons, enabling the host cell to generate piRNAs against active retrotransposons., Our observations confirm the pivotal role of piRNA-mediated silencing in defending the genome against selfish transposition, yet also suggest limits to the optimization of host genome defense., Analysis of piRNA-mediated silencing of active TEs in Drosophila melanogaster suggests limits on the evolution of host genome defense, The Piwi-interacting RNA (piRNA) pathway defends animal genomes against the harmful consequences of transposable element (TE) infection by imposing small-RNA-mediated silencing., A novel organelle, the piNG-body, in the nuage of Drosophila male germ cells is associated with piRNA-mediated gene silencing., Proteins of the PIWI subfamily Aub and AGO3 associated with the germline-specific perinuclear granules (nuage) are involved in the silencing of retrotransposons and other selfish repetitive elements in the Drosophila genome. , Telomeric retroelements HeT-A, TART and TAHRE, which are involved in telomere maintenance in Drosophila, are also the targets of piRNA-mediated silencing, Mechanism of the piRNA-mediated silencing of Drosophila telomeric retrotransposons., Gene silencing mechanisms mediated by Aubergine piRNA complexes in Drosophila male gonad., The epigenetic trans-silencing effect in Drosophila involves maternally-transmitted small RNAs whose production depends on the piRNA pathway and HP1., Here, we show that mutations in squash and zucchini, which are involved in the piwi-interacting RNA (piRNA) silencing pathway, strongly affect TSE, MVH in piRNA processing and gene silencing of retrotransposons, piRNA-mediated silencing in Drosophila germlines., These have shed light not only on the molecular mechanisms of gene silencing mediated by piRNAs and PIWI proteins, but also on their intriguing relationship with cellular genes that have been shown to be important for gametogenesis and fertility., The most abundant piRNAs were those corresponding to antisense transcripts of Suppressor of Stellate [Su(Ste)] genes known to be involved in Stellate gene silencing, To determine the capacity of piRNA-mediated silencing, we introduced reporter genes into Drosophila OSS cells, which express microRNAs (miRNAs) and piRNAs, and compared the Piwi pathway to the Argonaute pathway in gene regulation, PIWI-interacting small non-coding RNAs (piRNAs) are genetic and epigenetic regulatory factors in germline cells, where they maintain genome stability, are involved in RNA silencing and regulate gene expression, The piNG-body contains ribonucleoprotein complexes involved in piRNA-silencing of genome repeats including transposons in premeiotic spermatocytes with aid of short piRNAs, Our results show that the piRNA pathway can be used as a tool for sequence-specific gene silencing in germ cells and support the idea that the piRNA generating regions serve as traps for retrotransposons, enabling the host cell to generate piRNAs against active retrotransposons, Recent studies have revealed not only the biogenesis of piRNAs and their roles in transposon silencing, but also the function of the Piwi-piRNA pathway in epigenetic and post-transcriptional regulation of gene expression, A growing number of studies on piRNAs have investigated piRNA-mediated gene silencing, including piRNA biogenesis, These have shed light not only on the molecular mechanisms of gene silencing mediated by piRNAs and PIWI proteins, but also on their intriguing relationship with cellular genes that have been shown to be important for gametogenesis and fertility, Telomeric retroelements HeT-A, TART and TAHRE, which are involved in telomere maintenance in Drosophila, are also the targets of piRNA-mediated silencing. , MVH in piRNA processing and gene silencing of retrotransposons., To determine the capacity of piRNA-mediated silencing, we introduced reporter genes into Drosophila OSS cells, which express microRNAs (miRNAs) and piRNAs, and compared the Piwi pathway to the Argonaute pathway in gene regulation. , Therefore piRNA-mediated transcriptional mode of silencing is involved in the control of retrotransposon expression in the Drosophila germline., Panoramix enforces piRNA-dependent cotranscriptional silencing., The most abundant piRNAs were those corresponding to antisense transcripts of Suppressor of Stellate [Su(Ste)] genes known to be involved in Stellate gene silencing., Our results indicate that piRNAs are involved in a posttranscriptional gene-silencing mechanism resulting in RNA nuclear accumulation.[SEP]Relations: PIWIL1 has relations: bioprocess_protein with gene silencing by RNA, bioprocess_protein with gene silencing by RNA, bioprocess_protein with piRNA metabolic process, bioprocess_protein with piRNA metabolic process, molfunc_protein with piRNA binding, molfunc_protein with piRNA binding. PIWI-interacting RNA (piRNA) biogenesis has relations: pathway_protein with TDRD12, pathway_protein with TDRD12, pathway_protein with MAEL, pathway_protein with MAEL. Definitions: Aubergine defined as following: A plant species of the genus SOLANUM, family SOLANACEAE. The fruit is a large, egg-shaped berry, varying in color from dark purple to red, yellowish, or white. The leaves are large and ovate. The flowers are pendant, violet, and two inches across.. sequences defined as following: The sequence of nucleotide residues along a DNA chain.. genome defined as following: Anatomical set of genes in all the chromosomes.. AGO3 defined as following: Protein argonaute-3 (860 aa, ~97 kDa) is encoded by the human AGO3 gene. This protein is involved in RNA-mediated silencing of translation.. stem cells defined as following: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.. piwi-interacting RNA defined as following: Single-stranded RNA molecules that are expressed in animal cells and form complexes with Piwi proteins. They are involved in transcriptional gene silencing.. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.. complexes defined as following: A molecular entity formed by loose association involving two or more component molecular entities. The bonding between the components is normally weaker than in a covalent bond.. Proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. nuage defined as following: A small cytoplasmic, non-membranous RNA/protein complex aggregate in the primordial germ cells of many higher eukaryotes. [GOC:dph, GOC:kmv, PMID:11262230]. HP1 defined as following: A protein family comprised of chromo and chromo shadow domain-containing, methyl-lysine binding proteins that are localized to heterochromatin. These proteins are involved in gene silencing, transcriptional activation, and the formation and stabilization of heterochromatin.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. microRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. spermatocytes defined as following: Male germ cells derived from SPERMATOGONIA. The euploid primary spermatocytes undergo MEIOSIS and give rise to the haploid secondary spermatocytes which in turn give rise to SPERMATIDS.. essential genes defined as following: Those genes found in an organism which are necessary for its viability and normal function.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. germ cells defined as following: The reproductive cells in multicellular organisms at various stages during GAMETOGENESIS.. transposable element defined as following: Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.. Stellate defined as following: A term that refers to lesions or cells that are shaped like stars.. organisms defined as following: A living entity.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. locus defined as following: The position of a gene or a chromosomal marker on a chromosome; also, a stretch of DNA at a particular place on a particular chromosome. The use of locus is sometimes restricted to mean regions of DNA that are expressed.. RNA defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. telomere defined as following: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.. TE defined as following: A noninvasive test that is used to stage fibrosis in the liver. A 50-MHz wave is passed into the liver from a small transducer on the end of an ultrasound probe which measures the velocity of the shear wave (in meters per second) as this wave passes through the liver. The shear wave velocity can then be converted into liver stiffness. This technique is an alternative to liver biopsy.. piRNAs defined as following: Single-stranded RNA molecules that are expressed in animal cells and form complexes with Piwi proteins. They are involved in transcriptional gene silencing..", "label": "yes"} {"id": "converted_1978", "sentence1": "Do histone variant mH2A (macro-H2A) levels decrease upon differentiation?", "sentence2": "Through manipulation of macroH2A isoforms, we further demonstrate that macroH2A2 is the predominant barrier to reprogramming., In particular, we find macroH2A isoforms to be highly enriched at target genes of the K27me3 demethylase, Utx, which are reactivated early in iPS reprogramming, Therefore, we propose that macroH2A isoforms provide a redundant silencing layer or terminal differentiation 'lock' at critical pluripotency genes that presents as an epigenetic barrier when differentiated cells are challenged to reprogram., Histone variant macroH2A confers resistance to nuclear reprogramming, Resistance to reprogramming is associated with incorporation of the histone variant macroH2A, which is retained on the Xi of differentiated cells, but absent from the Xi of EpiSCs., We highlight the role of macroH2A in the establishment and maintenance of differentiated states and we discuss its still poorly recognized function in transcriptional activation., Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency., MacroH2A.1 was found to be present at low levels upon the establishment of pluripotency in the inner cell mass and epiblast, but it was highly enriched in the trophectoderm and differentiated somatic cells later in mouse development., Chromatin immunoprecipitation revealed that macroH2A.1 is incorporated in the chromatin of regulatory regions of pluripotency genes in somatic cells such as mouse embryonic fibroblasts and adult neural stem cells, but not in embryonic stem cells., In addition, overexpression of macroH2A isoforms prevented efficient reprogramming of epiblast stem cells to naïve pluripotency. , Macro histone variants are critical for the differentiation of human pluripotent cells, Here we show that the knockdown of macro histone variants impaired the in vitro and in vivo differentiation of human pluripotent cells, likely through defects in the silencing of pluripotency-related genes, Furthermore, male and female mH2A-deficient ESCs proliferate normally under pluripotency culture conditions, and respond to several standard differentiation procedures efficiently.[SEP]Relations: regulation of RNA polymerase I regulatory region sequence-specific DNA binding has relations: bioprocess_bioprocess with regulation of transcription regulatory region DNA binding, bioprocess_bioprocess with regulation of transcription regulatory region DNA binding, bioprocess_bioprocess with negative regulation of RNA polymerase I regulatory region sequence-specific DNA binding, bioprocess_bioprocess with negative regulation of RNA polymerase I regulatory region sequence-specific DNA binding. cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome has relations: disease_phenotype_positive with Decreased response to growth hormone stimuation test, disease_phenotype_positive with Decreased response to growth hormone stimuation test. RNA localization to chromatin has relations: bioprocess_protein with HNRNPU, bioprocess_protein with HNRNPU. Bite cells has relations: disease_phenotype_positive with hereditary stomatocytosis, disease_phenotype_positive with hereditary stomatocytosis. Definitions: Histone variant defined as following: A family of proteins that can substitute for the core canonical histones (H3, H4, H2A, H2B) in nucleosomes. Unlike canonical core histones, variant histones may be expressed during the entire cell cycle and the genes encoding histone variants usually are found outside histone gene clusters, contain introns and their transcribed mRNAs have a polyadenine tail.. isoforms defined as following: Refers to variants of the same protein which can be separated on special conducting media using electrophoresis. The differences may arise from genetically determined differences in primary structure or by modification of the same primary sequence.. regulatory regions defined as following: Nucleic acid sequences involved in regulating the expression of genes.. Utx defined as following: Human KDM6A wild-type allele is located in the vicinity of Xp11.2 and is approximately 238 kb in length. This allele, which encodes lysine-specific demethylase 6A protein, plays a role in the regulation of histone methylation. Loss of function mutations occur in multiple tumor types.. embryonic stem cells defined as following: Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.. somatic cells defined as following: Nucleated cell which has one or more diploid sets (46 pairs) of chromosomes.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. epiblast defined as following: The outer germ layer of a BLASTOCYST or BLASTULA, precursor of ectoderm and mesoderm.. neural stem cells defined as following: Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. mH2A defined as following: A histone protein that is comprised of a histone H2A domain, which allows interaction with the nucleosome, and a macro domain, which may bind to ADP-ribose. This protein can substitute for histone H2A in the nucleosomal complex and plays a role in transcriptional repression and X chromosome inactivation..", "label": "no"} {"id": "converted_1898", "sentence1": "Is Stat4 a transcription factor?", "sentence2": "transcription factors T-bet and STAT4, STAT4 is a member of the signal transducer and activator of transcription (STAT) family of molecules that localizes to the cytoplasm. STAT4 regulates various genes expression as a transcription factor after it is phosphorylated, dimerizes and translocates to the nucleus. , STAT4 is a latent cytosolic factor that encodes a transcription factor transmitting signals stimulated by cytokines. , To investigate the role of signal transduction and activation of transcription 4 (STAT4) in the development and progression of human hepatocellular carcinoma (HCC)[SEP]Relations: transcription factor binding has relations: molfunc_protein with STAT3, molfunc_protein with STAT3, molfunc_protein with IRF4, molfunc_protein with IRF4, molfunc_protein with E2F4, molfunc_protein with E2F4, molfunc_protein with CHD4, molfunc_protein with CHD4, molfunc_protein with NFATC4, molfunc_protein with NFATC4. Definitions: nucleus defined as following: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). transcription factor defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. STAT4 defined as following: Signal transducer and activator of transcription 4 (748 aa, ~86 kDa) is encoded by the human STAT4 gene. This protein is involved in transcriptional activation and signal transduction.. molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. T-bet defined as following: This gene is involved in the regulation of cytokine gene expression.. Stat4 defined as following: Signal transducer and activator of transcription 4 (748 aa, ~86 kDa) is encoded by the human STAT4 gene. This protein is involved in transcriptional activation and signal transduction..", "label": "yes"} {"id": "converted_918", "sentence1": "Is oxalate renal excretion increased after bariatric surgery?", "sentence2": "Despite the fact that bariatric surgery-induced weight loss is associated with a significant decrease in morbidity and mortality and improvement in renal function, bariatric surgery has recently been shown to be associated with a significant risk of nephrolithiasis. The main risk factor for nephrolithiasis is increased excretion of urinary oxalate., Enteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy must be considered with the other risks of RYGBP., The urinary excretion of oxalate was high: 1.112 mumol/24 h (normal range: 55-400 mumol/24 h), and citrate excretion was low: 1.48 mmol/24 h (normal range: 2-5 mmol/24 h). , Hyperoxaluria in patients with JIB was found to be a result of hyperabsorption of oxalate, and these patients displayed altered oxalate kinetics with continued urinary excretion of orally administered 14C-oxalate for more than 48 hours. , Malabsorption of calcium and low fasting urinary calcium excretion in the JIB patients were associated with high tubular reabsorption of calcium, the latter presumably attributable to a compensatory increase in circulating parathyroid hormone (PTH). In most recurrent renal stone formers the urinary calcium concentration was increased, with an inverse relationship to serum PTH, indicating intestinal hyperabsorption of calcium. A[SEP]Relations: Nephropathy has relations: drug_effect with Oxaliplatin, drug_effect with Oxaliplatin, drug_effect with Oxacillin, drug_effect with Oxacillin, drug_effect with Irbesartan, drug_effect with Irbesartan, drug_effect with Ioxaglic acid, drug_effect with Ioxaglic acid, drug_effect with Ranitidine, drug_effect with Ranitidine. Definitions: calcium defined as following: A dietary supplement containing the mineral calcium.. citrate defined as following: The determination of the amount of citrate present in a sample.. Malabsorption defined as following: General term for a group of MALNUTRITION syndromes caused by failure of normal INTESTINAL ABSORPTION of nutrients.. Hyperoxaluria defined as following: Excretion of an excessive amount of OXALATES in the urine.. PTH defined as following: A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.. urinary defined as following: The duct which coveys URINE from the pelvis of the KIDNEY through the URETERS, BLADDER, and URETHRA.. oxalate defined as following: A salt or ester of oxalic acid..", "label": "yes"} {"id": "converted_352", "sentence1": "Are there studies representing the involvement of Notch mutations in neurodegenerative diseases such as Down syndrome, Pick's and Prion's disease, and cadasil syndrome?", "sentence2": "he Notch signaling pathway plays a critical role in maintaining the balance between cell proliferation, differentiation and apoptosis, and is a highly conserved signaling pathway that regulates normal development in a context- and dose-dependent manner. Dysregulation of Notch signaling has been suggested to be key events in a variety of hematological malignancies. Notch1 signaling appears to be the central oncogenic trigger in T cell acute lymphoblastic leukemia (T-ALL), in which the majority of human malignancies have acquired mutations that lead to constitutive activation of Notch1 signaling., In a forward genetic screen for mutations that alter intracellular Notch receptor trafficking in Drosophila melanogaster, we recovered mutants that disrupt genes encoding serine palmitoyltransferase and acetyl-CoA carboxylase., Signaling pathways have become a major source of targets for novel therapies in hepatocellular carcinoma (HCC). Survival benefits achieved with sorafenib, a multikinase inhibitor, are unprecedented and underscore the importance of improving our understanding of how signaling networks interact in transformed cells., Notch-1 immunoexpression is increased in Alzheimer's and Pick's disease, (PSEN1) is the major locus for mutations causing familial Alzheimer's disease (FAD) and is also mutated in Pick disease of brain, familial acne inversa and dilated cardiomyopathy. It is a critical facilitator of Notch signalling and many other signalling pathways and protein cleavage events including production of the Amyloidβ (Aβ) peptide from the AMYLOID BETA A4 PRECURSOR PROTEIN (APP, As beta-APP and Notch are both processed by gamma-secretase, we analyzed expression of the Notch signaling pathway in the adult DS brain and in a model system for DS, human trisomy 21 fibroblasts by quantitative PCR. In adult DS cortex we found that Notch1, Dll1 and Hes1 expression is up-regulated. Moreover, DS fibroblasts and Alzheimer disease cortex also show overexpression of Notch1 and Dll1, indicating that enhanced beta-APP processing found in both DS and AD could be instrumental in these changes, A systems biology approach to Down syndrome: identification of Notch/Wnt dysregulation in a model of stem cells aging, Notch3 gene has been recently identified as a causative gene for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)[SEP]Relations: NOTCH3 has relations: disease_protein with cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy,, disease_protein with cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy,, disease_protein with CARASIL syndrome, disease_protein with CARASIL syndrome, disease_protein with lateral meningocele syndrome, disease_protein with lateral meningocele syndrome, disease_protein with dementia (disease), disease_protein with dementia (disease). CARASIL syndrome has relations: disease_protein with NOTCH3, disease_protein with NOTCH3. Definitions: stem cells defined as following: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.. FAD defined as following: A condensation product of riboflavin and adenosine diphosphate. The coenzyme of various aerobic dehydrogenases, e.g., D-amino acid oxidase and L-amino acid oxidase. (Lehninger, Principles of Biochemistry, 1982, p972). CADASIL defined as following: A hereditary cerebrovascular disorder caused by mutations in the Notch 3 gene. It is characterized by alterations of the muscular wall of the small vessels in the brain, resulting in transient ischemic attacks. It may lead to cognitive problems and dementia.. T cell acute lymphoblastic leukemia defined as following: A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.. Hes1 defined as following: This gene is involved in the modulation of transcription.. gamma-secretase defined as following: A protein complex that plays a role in the intramembrane cleavage of integral proteins such as Notch receptors and amyloid beta A4 protein.. Down syndrome defined as following: A chromosome disorder associated either with an extra CHROMOSOME 21 or an effective TRISOMY for chromosome 21. Clinical manifestations include HYPOTONIA, short stature, BRACHYCEPHALY, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, single transverse palmar crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213). Dll1 defined as following: This gene is involved in notch signaling.. Notch1 defined as following: Human NOTCH1 wild-type allele is located in the vicinity of 9q34.3 and is approximately 51 kb in length. This allele, which encodes neurogenic locus notch homolog protein 1 protein, plays a role in developmental processes by controlling cell fate decisions.. Pick disease defined as following: A rare form of DEMENTIA that is sometimes familial. Clinical features include APHASIA; APRAXIA; CONFUSION; ANOMIA; memory loss; and personality deterioration. This pattern is consistent with the pathologic findings of circumscribed atrophy of the poles of the FRONTAL LOBE and TEMPORAL LOBE. Neuronal loss is maximal in the HIPPOCAMPUS, entorhinal cortex, and AMYGDALA. Some ballooned cortical neurons contain argentophylic (Pick) bodies. (From Brain Pathol 1998 Apr;8(2):339-54; Adams et al., Principles of Neurology, 6th ed, pp1057-9). acetyl-CoA carboxylase defined as following: A carboxylating enzyme that catalyzes the conversion of ATP, acetyl-CoA, and HCO3- to ADP, orthophosphate, and malonyl-CoA. It is a biotinyl-protein that also catalyzes transcarboxylation. The plant enzyme also carboxylates propanoyl-CoA and butanoyl-CoA (From Enzyme Nomenclature, 1992) EC 6.4.1.2.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. hepatocellular carcinoma defined as following: A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.. PSEN1 defined as following: Presenilin-1 (467 aa, ~53 kDa) is encoded by the human PSEN1 gene. This protein plays a role in the mediation of proteolysis.. dilated cardiomyopathy defined as following: Cardiomyopathy which is characterized by dilation and contractile dysfunction of the left and right ventricles. It may be idiopathic, or it may result from a myocardial infarction, myocardial infection, or alcohol abuse. It is a cause of congestive heart failure.. mutants defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. malignancies defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. APP defined as following: An application designed specifically for use on a smartphone.. serine palmitoyltransferase defined as following: Serine palmitoyltransferase 1 (473 aa, ~53 kDa) is encoded by the human SPTLC1 gene. This protein plays a role in the biosynthesis of sphingolipids.. sorafenib defined as following: A synthetic compound targeting growth signaling and angiogenesis. Sorafenib blocks the enzyme RAF kinase, a critical component of the RAF/MEK/ERK signaling pathway that controls cell division and proliferation; in addition, sorafenib inhibits the VEGFR-2/PDGFR-beta signaling cascade, thereby blocking tumor angiogenesis.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. locus defined as following: The position of a gene or a chromosomal marker on a chromosome; also, a stretch of DNA at a particular place on a particular chromosome. The use of locus is sometimes restricted to mean regions of DNA that are expressed.. Notch3 gene defined as following: This gene plays a role in both intercellular signaling and cell fate determination.. human defined as following: Members of the species Homo sapiens.. hematological malignancies defined as following: Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.. mutated defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. leukoencephalopathy defined as following: Any of various diseases affecting the white matter of the central nervous system.. cadasil syndrome defined as following: A hereditary cerebrovascular disorder caused by mutations in the Notch 3 gene. It is characterized by alterations of the muscular wall of the small vessels in the brain, resulting in transient ischemic attacks. It may lead to cognitive problems and dementia.. neurodegenerative diseases defined as following: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures..", "label": "yes"} {"id": "converted_3326", "sentence1": "Is there a role for MRPL53 in cancer?", "sentence2": "MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach., A valuable approach to understand how individual and population genetic differences can predispose to disease is to assess the impact of genetic variants on cellular functions (e.g., gene expression) of cell and tissue types related to pathological states. To understand the genetic basis of nonsyndromic cleft lip with or without cleft palate (NSCL/P) susceptibility, a complex and highly prevalent congenital malformation, we searched for genetic variants with a regulatory role in a disease-related tissue, the lip muscle (orbicularis oris muscle [OOM]), of affected individuals. From 46 OOM samples, which are frequently discarded during routine corrective surgeries on patients with orofacial clefts, we derived mesenchymal stem cells and correlated the individual genetic variants with gene expression from these cultured cells. Through this strategy, we detected significant cis-eQTLs (i.e., DNA variants affecting gene expression) and selected a few candidates to conduct an association study in a large Brazilian cohort (624 patients and 668 controls). This resulted in the discovery of a novel susceptibility locus for NSCL/P, rs1063588, the best eQTL for the MRPL53 gene, where evidence for association was mostly driven by the Native American ancestry component of our Brazilian sample. MRPL53 (2p13.1) encodes a 39S protein subunit of mitochondrial ribosomes and interacts with MYC, a transcription factor required for normal facial morphogenesis. [SEP]Relations: mitochondrial ribosome has relations: cellcomp_protein with MRPL9, cellcomp_protein with MRPL9, cellcomp_protein with MRPL39, cellcomp_protein with MRPL39, cellcomp_protein with MRPL51, cellcomp_protein with MRPL51, cellcomp_protein with MRPL11, cellcomp_protein with MRPL11, cellcomp_protein with MRPL13, cellcomp_protein with MRPL13. Definitions: mesenchymal stem cells defined as following: An undifferentiated stromal cell with the ability to develop into the cells that form distinct mesenchymal tissues; such as bone, muscle, connective tissue, blood vessels, and lymphatic tissue.. MYC defined as following: Myc proto-oncogene protein (439 aa, ~49 kDa) is encoded by the human MYC gene. This protein plays a role in the regulation of transcription and cell proliferation.. cultured cells defined as following: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.. transcription factor defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. mitochondrial ribosomes defined as following: A ribosome found in the mitochondrion of a eukaryotic cell; contains a characteristic set of proteins distinct from those of cytosolic ribosomes. [GOC:mah, ISBN:0198506732]. congenital malformation defined as following: Malformations of organs or body parts during development in utero.. cancer defined as following: A malignant tumor at the original site of growth..", "label": "no"} {"id": "converted_4697", "sentence1": "Is disruption of immune regulation mechanisms associated with adverse pregnancy outcomes, including preeclampsia (PE)?", "sentence2": " Maternal systemic and placental inflammatory responses participate in the pathogenesis of hypertensive disorders of pregnancy including preeclampsia, a pregnancy-specific syndrome, although the role of inflammation remains unclear. , Our results indicate these proteins are new factors that play important roles in the immunological pathomechanism of preeclampsia., Inflammation and oxidative stress at the maternal-fetal interface characterize the placental dysfunction that underlies the pregnancy disorder preeclampsia., The abnormal expression of Tim-3 on MDSC might be involved in the pathogenesis of PE, and could be a marker to evaluate the immune function in PE., Maternal immune tolerance is important for maintaining pregnancy, and researchers have increasingly focused on the critical roles of cytokines in the pathogenesis of PE in recent years., Disruption of well-controlled immune functions leads to infertility, placental inflammation, and numerous pregnancy complications, including preeclampsia (PE)., Effect of Endogenic and Exogenic Oxidative Stress Triggers on Adverse Pregnancy Outcomes: Preeclampsia, Fetal Growth Restriction, Gestational Diabetes Mellitus and Preterm Birth., Disruption of complex immune regulation mechanisms is associated with adverse pregnancy outcomes, including preeclampsia (PE)., In addition, it has been demonstrated that immune disturbance may be responsible for some adverse pregnancy outcomes such as preeclampsia (PE), recurrent spontaneous abortion (RSA) and intrauterine growth restriction (IUGR)., esponse. In previous models of preeclampsia (PE), defective immune function caused by disruption of lymphangiogenesis was shown to be involved in the disease pathophy, OBJECTIVE: Increased oxidative stress and immune dysfunction are implicated in preeclampsia (PE) and may contribute to the two- to fourfold increase in PE prevalence among women with type 1 , r, in preeclampsia, the regulation of immune responses is disrupted as a result of aberrant activation of innate immune cells and imbalanced differentiation of T-helper cell subsets creating a cytotoxic environment in uter, Disruption in the Regulation of Immune Responses in the Placental Subtype of Preeclampsia, a disrupted immune system might be a predisposing factor or result of placental oxidative stress or excessive inflammation in preeclampsia. Preeclampsia c, clude insufficient control of inflammation, failure of tolerance toward paternal antigens at the fetal-maternal interface, and subsequent over- or insufficient activation of immune mediators. It is als, PROBLEM: The purpose of this study is to clarify whether the disruption of immune regulation occurs in early pregnancy before the clinical manifestations of pre, s review, we focus on the role of excessive systemic inflammation as the result of a dysregulated immune system in the development of preeclampsia. These, PROBLEM: The purpose of this study is to clarify whether the disruption of immune regulation occurs in early pregnancy before the clinical manifestations of pree, However, in preeclampsia, the regulation of immune responses is disrupted as a result of aberrant activation of innate immune cells and imbalanced differentiation of T-helper cell subsets creating a cytotoxic environment in utero., In conclusion, a disrupted immune system might be a predisposing factor or result of placental oxidative stress or excessive inflammation in preeclampsia., esponse. In previous models of preeclampsia (PE), defective immune function caused by disruption of lymphangiogenesis was shown to be involved in the disease pathoph, Disruption of this immune balance and/or inadequate placental perfusion is believed to be associated with a lot of pregnancy-related complications, such as recurrent spontaneous abortion, pre-eclampsia, and fetal intrauterine growth restriction., Therefore, a delicate immune balance is critical for the maintenance of a successful pregnancy, while disruption of this balance can induce complications such as implantation failure, miscarriage, preterm birth/labor, preeclampsia and fetal growth restriction., antigens during pregnancy. Disruption of complex immune regulation mechanisms is associated with adverse pregnancy outcomes, including preeclampsia (P, ccessful pregnancy. It has been demonstrated that innate immune disturbances may be responsible for some adverse pregnancy outcomes such as preeclamps, ever, in preeclampsia, the regulation of immune responses is disrupted as a result of aberrant activation of innate immune cells and imbalanced differ, PROBLEM: The purpose of this study is to clarify whether the disruption of immune regulation occurs in early pregnancy before the clinical manifestations of preeclampsia, However, immune maladaptation and hemostatic imbalance have been suggested to be responsible for adverse pregnant outcomes, such as preeclampsia (PE), miscarriage, recurrent spontaneous abortion (RSA) and intrauterine growth restriction (IUGR)., PROBLEM: The purpose of this study is to clarify whether the disruption of immune regulation occurs in early pregnancy before the clinical manifestations of preeclampsia.METHOD OF STUDY: The serum concentrations of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) were determined by using enzyme-linked immunoadsorbent assay (ELISA) in the first trimester of pregnancy in women who had preeclampsia develop after 28 weeks of pregnancy (preeclamptic group) and in women who completed pregnancy uneventfully (control group).RESULTS: Serum concentrations of both IL-2 and TNF-alpha in the first trimester of the preeclamptic group were significantly higher than those of the control group.CONCLUSIONS: That the perturbation of feto-maternal immune regulation may precede the clinical manifestations of preeclampsia, which may be of relevance i, Preeclampsia can thus be considered a hyperinflammatory state associated with defective regulation of the immune system proposed as a key element in the pathological events of the placental subtype of this disorder., Disruption in the Regulation of Immune Responses in the Placental Subtype of Preeclampsia., It has been demonstrated that innate immune disturbances may be responsible for some adverse pregnancy outcomes such as preeclampsia (PE); hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome; intrauterine growth restriction (IUGR); and recurrent spontaneous abortion (RSA).[SEP]Relations: preeclampsia has relations: contraindication with Progesterone, contraindication with Progesterone, disease_disease with toxemia of pregnancy, disease_disease with toxemia of pregnancy, disease_phenotype_positive with Abnormality of the nervous system, disease_phenotype_positive with Abnormality of the nervous system, disease_disease with severe pre-eclampsia, disease_disease with severe pre-eclampsia, disease_phenotype_positive with Abnormality of the kidney, disease_phenotype_positive with Abnormality of the kidney. Definitions: Tim-3 defined as following: Human HAVCR2 wild-type allele is located in the vicinity of 5q33.3 and is approximately 57 kb in length. This allele, which encodes hepatitis A virus cellular receptor 2 protein, is involved in the activation of macrophages and helper T cells.. Inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. MDSC defined as following: A heterogeneous, immature population of myeloid cells that can suppress the activity of T-CELLS and NATURAL KILLER CELLS in the INNATE IMMUNE RESPONSE and ADAPTIVE IMMUNE RESPONSE. They play important roles in ONCOGENESIS; INFLAMMATION; and INFECTION.. IL-2 defined as following: Binding to interleukin-2. [GOC:jl]. PE defined as following: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to an ethanolamine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and ethanolamine and 2 moles of fatty acids.. preeclampsia defined as following: A complication of PREGNANCY, characterized by a complex of symptoms including maternal HYPERTENSION and PROTEINURIA with or without pathological EDEMA. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease.. TNF-alpha defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine tumor necrosis factor-alpha with antineoplastic properties. Tumor necrosis factor-alpha binds to and activates \"death receptors\" on the cell surface, resulting in apoptosis and cell death by the p53-independent extrinsic pathway. This agent also disrupts tumor vascularization. (NCI04). antigens defined as following: Substances that are recognized by the immune system and induce an immune reaction.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. fetal defined as following: Care provided the pregnant woman in order to prevent complications, and decrease the incidence of maternal and prenatal mortality.. IUGR defined as following: Failure of a FETUS to attain expected GROWTH.. immune dysfunction defined as following: Disorders caused by abnormal or absent immunologic mechanisms, whether humoral, cell-mediated, or both.. tumor necrosis factor-alpha defined as following: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.. interleukin-2 defined as following: Any recombinant analog of endogenous interleukin-2 (IL-2), a cytokine involved in intercellular communication related to cell differentiation, proliferation, inflammation, hematopoiesis, neuronal functions, and release of hormones. IL-2 binds to and activates specific receptors, triggering expression of specific genes, and may induce T cell-mediated tumor regression in some tumor types.. immune mediators defined as following: Any substance that induces, enhances, restores or suppresses the host's immune system, or an agent that utilizes or is derived from a component of the immune system.. placental defined as following: A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (CHORIONIC VILLI) derived from TROPHOBLASTS and a maternal portion (DECIDUA) derived from the uterine ENDOMETRIUM. The placenta produces an array of steroid, protein and peptide hormones (PLACENTAL HORMONES).. infertility defined as following: Complete inability to conceive or induce conception..", "label": "yes"} {"id": "converted_2150", "sentence1": "Is skin color affected by variations of the SLC24A5 gene?", "sentence2": "the alleles of single-nucleotide polymorphisms rs1426654 and rs1834640 (SLC24A5) associated with light skin pigmentation in Eurasian populati, Associations between five single nucleotide polymorphisms (SNPs) known to play a role in pigmentation (rs1426654-SLC24A5, rs1042602-TYR, rs16891982-SLC45A2, rs6058017-ASIP, and rs642742-KITLG) and MI measures were tested using standard one-way analysis of variance (ANOVA) within each population.[SEP]Relations: Sodium/Calcium exchangers has relations: pathway_protein with SLC24A5, pathway_protein with SLC24A5, pathway_protein with SLC24A4, pathway_protein with SLC24A4, pathway_protein with SLC24A2, pathway_protein with SLC24A2, pathway_protein with SLC24A3, pathway_protein with SLC24A3, pathway_protein with SLC24A1, pathway_protein with SLC24A1. Definitions: alleles defined as following: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.. SNPs defined as following: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.. SLC24A5 defined as following: Sodium/potassium/calcium exchanger 5 (500 aa, ~55 kDa) is encoded by the human SLC24A5 gene. This protein plays a role in calcium and potassium ion exchange for sodium in melanocytes.. SLC24A5 gene defined as following: Sodium/potassium/calcium exchanger 5 (500 aa, ~55 kDa) is encoded by the human SLC24A5 gene. This protein plays a role in calcium and potassium ion exchange for sodium in melanocytes..", "label": "yes"} {"id": "converted_1845", "sentence1": "Can the Micro-C XL method achieve mononucleosome resolution?", "sentence2": "We present Micro-C XL, an improved method for analysis of chromosome folding at mononucleosome resolution, We present Micro-C XL, an improved method for analysis of chromosome folding at mononucleosome resolution., Micro-C XL: assaying chromosome conformation from the nucleosome to the entire genome., Micro-C XL provides a single assay to interrogate chromosome folding at length scales from the nucleosome to the full genome.[SEP]Relations: nucleosome mobilization has relations: bioprocess_protein with POLE3, bioprocess_protein with POLE3, bioprocess_bioprocess with chromatin remodeling, bioprocess_bioprocess with chromatin remodeling, bioprocess_protein with BPTF, bioprocess_protein with BPTF, bioprocess_protein with ARID1A, bioprocess_protein with ARID1A, bioprocess_protein with INO80, bioprocess_protein with INO80. Definitions: nucleosome defined as following: A complex comprised of DNA wound around a multisubunit core and associated proteins, which forms the primary packing unit of DNA into higher order structures. [GOC:elh]. genome defined as following: Anatomical set of genes in all the chromosomes..", "label": "yes"} {"id": "converted_888", "sentence1": "Does replication timing affect the rate of somatic mutations?", "sentence2": "Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome, ll classes of substitutions are affected, suggesting a generalized mechanism involving replication time-dependent DNA damage, We show that mutation rate varies 6-fold across a single chromosome, that this variation is correlated with replication timing, and we propose a model to explain this variation that relies on the temporal separation of two processes for replicating past damaged DNA: error-free DNA damage tolerance and translesion synthesis., Recent studies revealed a long suspected replication-timing effect on mutation rate, but the mechanisms that regulate the increase in mutation rate as the genome is replicated remain unclear. , DNA repair systems, in general, are less efficient in late replicating heterochromatic regions compared to early replicating euchromatic regions of the genome., The mutational profile of the yeast genome is shaped by replication, the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions., Thus, we show that the leading replicating strands present an excess of C over G and of A over T in the genome of S. cerevisiae (reciprocally an excess of G + T over C + A in lagging strands), Late-replicating domains have higher divergence and diversity in Drosophila melanogaster, Recent evidence also suggests that late replication is associated with high mutability in yeast., Limited evidence from one chromosome arm in Drosophila melanogaster suggests the opposite pattern, with regions overlapping early-firing origins showing increased levels of diversity and divergence, The mutation rate for DNA mismatch repair null strains was approximately 1 mutation per genome per generation, 225-fold greater than the wild-type rate. The mutations were distributed randomly throughout the genome, independent of replication timing., Many single-nucleotide substitutions in cancer genomes arise because of errors in DNA replication, which is spatio-temporally stratified., Here we propose that DNA replication patterns help shape the mutational landscapes of normal and cancer genomes, Using data on five fully sequenced cancer types and two personal genomes, we determined that the frequency of intergenic single-nucleotide substitution is significantly higher in late DNA replication timing regions, even after controlling for a number of genomic features, we found that genomic regions in close spatial proximity to late-replicating domains display similar mutation spectra as the late-replicating regions themselves, In addition, certain chromosome rearrangements found in cancer cells and in cells exposed to ionizing radiation display a significant delay in replication timing of >3 hours that affects the entire chromosome(2,3). Recent work from our lab indicates that disruption of discrete cis-acting autosomal loci result in an extremely late replicating phenotype that affects the entire chromosome(4)., A conservative estimate is that at least 1-2% of new deleterious mutations affect some aspect of DNA replication, repair, or chromosome segregation. Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate., Drake calculates that lytic RNA viruses display spontaneous mutation rates of approximately one per genome while most have mutation rates that are approximately 0.1 per genome (Drake 1993). This constancy of germline mutation rates among microbial species need not necessarily mean constancy of the somatic mutation rates., A recent flurry of reports correlates replication timing (RT) with mutation rates during both evolution and cancer., DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability., Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate., In addition, this method allows for the unambiguous identification of chromosomal rearrangements that correlate with changes in replication timing that affect the entire chromosome.[SEP]Relations: adaptation to pheromone regulating conjugation with mutual genetic exchange has relations: bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with negative adaptation of signaling pathway, bioprocess_bioprocess with negative adaptation of signaling pathway. partial monosomy of the short arm of chromosome X has relations: disease_disease with atypical Norrie disease due to monosomy Xp11.3, disease_disease with atypical Norrie disease due to monosomy Xp11.3. Lacrimation abnormality has relations: disease_phenotype_positive with limbal stem cell deficiency, disease_phenotype_positive with limbal stem cell deficiency, disease_phenotype_positive with Waardenburg syndrome, disease_phenotype_positive with Waardenburg syndrome. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. cancer cells defined as following: Cells of, or derived from, a malignant tumor.. genome defined as following: Anatomical set of genes in all the chromosomes.. chromosome arm defined as following: Under the microscope chromosomes appear as thin, thread-like structures. They all have a short arm and long arm separated by a primary constriction called the centromere. The short arm is designated as p and the long arm as q.. yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. RNA viruses defined as following: Viruses whose genetic material is RNA..", "label": "yes"} {"id": "converted_28", "sentence1": "Proteomic analyses need prior knowledge of the organism complete genome. Is the complete genome of the bacteria of the genus Arthrobacter available?", "sentence2": "Complete genome sequence of Arthrobacter phenanthrenivorans type strain (Sphe3)., Complete genome sequence and metabolic potential of the quinaldine-degrading bacterium Arthrobacter sp. Rue61a., Here, we described the high quality draft genome sequence, annotations and the features ofArthrobactersp. B6., Complete genome sequence of Arthrobacter sp. ZXY-2 associated with effective atrazine degradation and salt adaptation., We announce here the draft genome sequence ofArthrobactersp. strain EpSL27, isolated from the stem and leaves of the medicinal plantEchinacea purpureaand able to inhibit human-pathogenic bacterial strains. , We report here the 4.6-Mb genome sequence of a nylon oligomer-degrading bacterium,Arthrobactersp. strain KI72., Arthrobacter alpinusR3.8 is a psychrotolerant bacterial strain isolated from a soil sample obtained at Rothera Point, Adelaide Island, close to the Antarctic Peninsula. Strain R3.8 was sequenced in order to help discover potential cold active enzymes with biotechnological applications. [SEP]Relations: Sodium chloride has relations: drug_effect with Epiphora, drug_effect with Epiphora, drug_effect with Thrombophlebitis, drug_effect with Thrombophlebitis, drug_drug with Tolvaptan, drug_drug with Tolvaptan. Electric Transmission Across Gap Junctions has relations: pathway_protein with GJA10, pathway_protein with GJA10, pathway_protein with PANX1, pathway_protein with PANX1. Definitions: leaves defined as following: Expanded structures, usually green, of vascular plants, characteristically consisting of a bladelike expansion attached to a stem, and functioning as the principal organ of photosynthesis and transpiration. (American Heritage Dictionary, 2d ed). salt defined as following: Sodium chloride used in foods.. stem defined as following: A type of TRANSMISSION ELECTRON MICROSCOPY in which the object is examined directly by an extremely narrow electron beam scanning the specimen point-by-point and using the reactions of the electrons that are transmitted through the specimen to create the image. It should not be confused with SCANNING ELECTRON MICROSCOPY.. bacteria defined as following: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.. organism defined as following: A living entity.. genome defined as following: Anatomical set of genes in all the chromosomes..", "label": "yes"} {"id": "converted_1171", "sentence1": "Is nicotinamide effective for skin cancer prevention?", "sentence2": "Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses., ESULTS: At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% (95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the placebo group (P=0.02). Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39]lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 months (P=0.01), 14% lower at 6 months (P<0.001), 20% lower at 9 months (P<0.001), and 13% lower at 12 months (P=0.001)., CONCLUSIONS: Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients., Nicotinamide is a safe, widely available vitamin that reduces the immune suppressive effects of UV, enhances DNA repair in keratinocytes and has shown promise in the chemoprevention of non-melanoma skin cancer. , In summary, nicotinamide, by enhancing DNA repair in melanocytes, is a potential agent for the chemoprevention of cutaneous melanoma., Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers. , Nicotinamide (vitamin B3) prevents UV-induced immunosuppression and carcinogenesis in mice, and solar-simulated (ss) UV-induced immunosuppression in humans., These results show that nicotinamide enhances two different pathways for repair of UV-induced photolesions, supporting nicotinamide's potential as an inexpensive, convenient and non-toxic agent for skin cancer chemoprevention., Recent double-blinded randomized controlled Phase 2 studies in heavily sun-damaged individuals have shown that oral nicotinamide significantly reduces premalignant actinic keratoses, and may reduce new non-melanoma skin cancers., No noteworthy between-group differences were found with respect to the number or types of adverse events during the 12-month intervention period, and there was no evidence of benefit after nicotinamide was discontinued.CONCLUSIONS: Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients. , Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses.METHODS: In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. , Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39]lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). , Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients., Nicotinamide has shown potential as a safe and effective intervention for the prevention of malignant and premalignant skin lesions., Nicotinamide, which protected against both UVB and UVA, is a promising agent for skin cancer prevention.[SEP]Relations: Nicotinamide has relations: contraindication with liver disease, contraindication with liver disease, contraindication with gallbladder disease, contraindication with gallbladder disease, contraindication with kidney disease, contraindication with kidney disease, contraindication with diabetes mellitus (disease), contraindication with diabetes mellitus (disease), contraindication with peptic ulcer disease, contraindication with peptic ulcer disease. Definitions: Nicotinamide defined as following: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and PELLAGRA. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.. cutaneous melanoma defined as following: A primary melanoma arising from atypical melanocytes in the skin. Precursor lesions include acquired and congenital melanocytic nevi, and dysplastic nevi. Several histologic variants have been recognized, including superficial spreading melanoma, acral lentiginous melanoma, nodular melanoma, and lentigo maligna melanoma.. vitamin B3 defined as following: The determination of the amount of Vitamin B3 present in a sample.. nonmelanoma skin cancers defined as following: A carcinoma that arises from the skin. Representative examples are basal cell carcinoma and squamous cell carcinoma.. humans defined as following: Members of the species Homo sapiens.. keratinocytes defined as following: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.. skin cancer defined as following: A primary or metastatic malignant neoplasm involving the skin. Primary malignant skin neoplasms most often are carcinomas (either basal cell or squamous cell carcinomas) or melanomas. Metastatic malignant neoplasms to the skin include carcinomas and lymphomas.. melanocytes defined as following: Mammalian pigment cells that produce MELANINS, pigments found mainly in the EPIDERMIS, but also in the eyes and the hair, by a process called melanogenesis. Coloration can be altered by the number of melanocytes or the amount of pigment produced and stored in the organelles called MELANOSOMES. The large non-mammalian melanin-containing cells are called MELANOPHORES.. actinic keratoses defined as following: White or pink lesions on the arms, hands, face, or scalp that arise from sun-induced DNA DAMAGE to KERATINOCYTES in exposed areas. They are considered precursor lesions to superficial SQUAMOUS CELL CARCINOMA.. vitamin defined as following: Organic substances that are required in small amounts for maintenance and growth, but which cannot be manufactured by the human body..", "label": "yes"} {"id": "converted_996", "sentence1": "Has Revlimid been approved by the US Food and Drug Administration?", "sentence2": "In the past decade, immunomodulatory drugs have been approved by the US Food and Drug Administration for the treatment of multiple myeloma (MM)-and a number of emerging agents that target the cellular pathways or proteins involved in the pathophysiology of MM are currently in development. Lenalidomide (Revlimid) and pomalidomide induce apoptosis and sensitize MM cells while demonstrating superior efficacy and better tolerability than thalidomide (Thalomid)., In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin. , In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin., Thalidomide, lenalidomide (Revlimid), and bortezomib (Velcade) are directed not only at MM cells but also at the BM milieu and have moved rapidly from the bench to the bedside and United States Food and Drug Administration approval to treat MM., Lenalidomide (CC-5013, Revlimid; Celgene Corporation, Summit, NJ), a thalidomide analogue, was granted approval by the U.S. Food and Drug Administration (FDA) on June 29, 2006, for use in combination with dexamethasone in patients with multiple myeloma (MM) who have received at least one prior therapy., Lenalidomide, an IMiD drug (a novel type of immunomodulating drug) was recently approved by the US Food and Drug Administration for the treatment of transfusion-dependent anemia in patients with myelodysplastic syndromes (MDS) and interstitial deletions of chromosome 5q [del(5q)], Lenalidomide, a second-generation immunomodulatory drug (IMiD), is approved by the US Food and Drug Administration for treatment of transfusion-dependent anemia in lower-risk MDS patients with deletion 5q chromosomal abnormality, In the past decade we have seen four new agents approved by the US Food and Drug Administration for treatment of multiple myeloma: the proteasome inhibitor (PI) bortezomib (Velcade), the immunomodulatory agents lenalidomide (Revlimid) and thalidomide (Thalomid), and liposomal doxorubicin., lenalidomide (CC5103 or revlimid) are recently approved for the treatment of multiple myeloma., In the past decade, immunomodulatory drugs have been approved by the US Food and Drug Administration for the treatment of multiple myeloma (MM)-and a number of emerging agents that target the cellular pathways or proteins involved in the pathophysiology of MM are currently in development. Lenalidomide (Revlimid) and pomalidomide induce apoptosis and sensitize MM cells while demonstrating superior efficacy and better tolerability than thalidomide (Thalomid).[SEP]Relations: Lenalidomide has relations: drug_drug with Reviparin, drug_drug with Reviparin. Pomalidomide has relations: drug_drug with Reviparin, drug_drug with Reviparin, drug_drug with Revefenacin, drug_drug with Revefenacin. Bortezomib has relations: drug_drug with Reviparin, drug_drug with Reviparin. Thalidomide has relations: drug_drug with Reviparin, drug_drug with Reviparin. Definitions: drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. thalidomide defined as following: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.. myelodysplastic syndromes defined as following: Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.. dexamethasone defined as following: An anti-inflammatory 9-fluoro-glucocorticoid.. lenalidomide defined as following: A thalidomide analog with potential antineoplastic activity. Lenalidomide inhibits TNF-alpha production, stimulates T cells, reduces serum levels of the cytokines vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and inhibits angiogenesis. This agent also promotes G1 cell cycle arrest and apoptosis of malignant cells.. NJ defined as following: State bounded on the north by New York and Pennsylvania, on the east by New York and the Atlantic Ocean, on the south by Delaware Bay, and on the west by Pennsylvania.. pomalidomide defined as following: An orally bioavailable derivative of thalidomide with potential immunomodulating, antiangiogenic and antineoplastic activities. Although its exact mechanism of action has yet to be fully elucidated, pomalidomide appears to inhibit TNF-alpha production, enhance the activity of T cells and natural killer (NK) cells and enhance antibody-dependent cellular cytotoxicity (ADCC). In addition, pomalidomide may inhibit tumor angiogenesis, promote cell cycle arrest in susceptible tumor cell populations, and stimulate erythropoeisis.. MM defined as following: A unit of concentration (molarity unit) equal to one thousandth of a mole (10E-3 mole) of solute per one liter of solution.. bortezomib defined as following: A pyrazine and boronic acid derivative that functions as a reversible PROTEASOME INHIBITOR. It is used as an ANTINEOPLASTIC AGENT in the treatment of MULTIPLE MYELOMA and MANTLE CELL LYMPHOMA.. multiple myeloma defined as following: A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.. PI defined as following: Backflow of blood from the PULMONARY ARTERY into the RIGHT VENTRICLE due to imperfect closure of the PULMONARY VALVE.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary..", "label": "yes"} {"id": "converted_3248", "sentence1": "Is endotrophin derived from collagen?", "sentence2": "endotrophin production from type IV collagen, High levels of COL6A3 and its cleaved product, endotrophin (ETP), Endotrophin is released from COL VI[SEP]Relations: collagen type IV trimer has relations: cellcomp_protein with OTOL1, cellcomp_protein with OTOL1, cellcomp_protein with COL4A1, cellcomp_protein with COL4A1, cellcomp_protein with COL4A5, cellcomp_protein with COL4A5, cellcomp_protein with COL4A3, cellcomp_protein with COL4A3, cellcomp_protein with COL4A2, cellcomp_protein with COL4A2. Definitions: COL6A3 defined as following: Collagen alpha-3(VI) chain (3177 aa, ~344 kDa) is encoded by the human COL6A3 gene. This protein plays a role in extracellular matrix formation and cell-matrix adhesion in connective tissues.. endotrophin defined as following: Endotrophin is encoded by the human COL6A3 gene. This protein is involved in macrophage infiltration, fibrosis and epithelial-mesenchymal transition.. type IV collagen defined as following: A non-fibrillar collagen found in the structure of BASEMENT MEMBRANE. Collagen type IV molecules assemble to form a sheet-like network which is involved in maintaining the structural integrity of basement membranes. The predominant form of the protein is comprised of two alpha1(IV) subunits and one alpha2(IV) subunit, however, at least six different alpha subunits can be incorporated into the heterotrimer.. collagen defined as following: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH)..", "label": "yes"} {"id": "converted_1402", "sentence1": "Are there Conserved Noncoding Elements (CNEs) in plant genomes?", "sentence2": "Conservation and functional element discovery in 20 angiosperm plant genomes, The detailed view of conservation across angiosperms revealed not only high coding-sequence conservation but also a large set of previously uncharacterized intergenic conservation, Conserved noncoding sequences highlight shared components of regulatory networks in dicotyledonous plants, Using a comparative genomics approach with four dicotyledonous plant species (Arabidopsis thaliana, papaya [Carica papaya], poplar [Populus trichocarpa], and grape [Vitis vinifera]), we detected hundreds of CNSs upstream of Arabidopsis genes, Long identical multispecies elements in plant and animal genomes., Using an alignment-free information-retrieval approach, we have comprehensively identified all long identical multispecies elements (LIMEs), which include both syntenic and nonsyntenic regions, of at least 100 identical base pairs shared by at least two genomes, In contrast, among six plant genomes, we only found nonsyntenic LIMEs, Although complex LIMEs were found in both animal and plant genomes, they differed significantly in their composition and copy number, Ultraconserved elements between the genomes of the plants Arabidopsis thaliana and rice, We consequently compared the genomes of Arabidopsis thaliana and rice, which diverged about 200 million years ago, and identified 25 ultraconserved elements that are longer than 100 bp, ultraconserved elements in plants tend to occur in clusters and locate at noncoding regions, the functions of these plant ultraconserved elements and the reasons why they are practically frozen during the evolution of millions of years remain a mystery, Conserved noncoding sequences in the grasses, Using a local sequence alignment set to deliver only significant alignments, we found one or more CNSs in the noncoding regions of the majority of genes studied. Grass genes have dramatically fewer and much smaller CNSs than mammalian genes, Conserved noncoding sequences among cultivated cereal genomes identify candidate regulatory sequence elements and patterns of promoter evolution, Surveys for conserved noncoding sequences (CNS) among genes from monocot cereal species were conducted to assess the general properties of CNS in grass genomes and their correlation with known promoter regulatory elements, Comparisons of orthologous maize-rice and maize-sorghum gene pairs identified 20 bp as a minimal length criterion for a significant CNS among grass genes, with few such CNS found to be conserved across rice, maize, sorghum, and barley[SEP]Relations: central nervous system has relations: anatomy_protein_present with NONO, anatomy_protein_present with NONO, anatomy_protein_present with CNP, anatomy_protein_present with CNP, anatomy_protein_present with CNBP, anatomy_protein_present with CNBP, anatomy_protein_present with CNPPD1, anatomy_protein_present with CNPPD1, anatomy_protein_present with CNR1, anatomy_protein_present with CNR1. Definitions: cereal defined as following: Seeds from grasses (POACEAE) which are important in the diet.. conservation defined as following: The maintenance of certain characteristics in an unchanged condition.. genomes defined as following: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.. promoter defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. plants defined as following: Multicellular, eukaryotic life forms of kingdom Plantae. Plants acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations. It is a non-taxonomical term most often referring to LAND PLANTS. In broad sense it includes RHODOPHYTA and GLAUCOPHYTA along with VIRIDIPLANTAE.. plant genomes defined as following: The genetic complement of a plant (PLANTS) as represented in its DNA.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"} {"id": "converted_2889", "sentence1": "Does Panitumumab prolong survival of biliary tract cancer patients?", "sentence2": "Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild-type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti-BIL study)., CONCLUSIONS: Panitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer. , No survival differences were observed: the median overall survival was 9.9 months in arm A and 10.2 months in arm B (P = .42). In a subgroup analysis, no differences in PFS according to the site of the primary tumor were observed; patients with intrahepatic cholangiocarcinoma treated with panitumumab may have had a survival benefit in comparison with the control group (15.1 vs 11.8 months, P = .13). , CONCLUSIONS\nPanitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer., CONCLUSIONS Panitumumab in combination with chemotherapy does not improve ORR, PFS and OS in patients with KRAS wild-type, advanced biliary cancer., Despite many clinical trials being conducted with molecular targeted agents including erlotinib, cetuximab, panitumumab, bevacizumab, sorafenib, cediranib, trametinib and vandetanib, no agent has shown to be effective for advanced biliary tract cancer., Adding panitumumab to standard protocols does not prolong survival but provokes additional adverse effects.[SEP]Relations: biliary tract cancer has relations: disease_disease with liver cancer, disease_disease with liver cancer, disease_protein with PRKACB, disease_protein with PRKACB, disease_disease with bile duct cancer, disease_disease with bile duct cancer. Panitumumab has relations: drug_drug with Bimagrumab, drug_drug with Bimagrumab, drug_drug with Afelimomab, drug_drug with Afelimomab. Definitions: gemcitabine defined as following: A broad-spectrum antimetabolite and deoxycytidine analogue with antineoplastic activity. Upon administration, gemcitabine is converted into the active metabolites difluorodeoxycytidine diphosphate (dFdCDP) and difluorodeoxycytidine triphosphate (dFdCTP) by deoxycytidine kinase. dFdCTP competes with deoxycytidine triphosphate (dCTP) and is incorporated into DNA. This locks DNA polymerase thereby resulting in \"masked termination\" during DNA replication. On the other hand, dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA synthesis. The reduction in the intracellular concentration of dCTP potentiates the incorporation of dFdCTP into DNA.. vandetanib defined as following: An orally bioavailable 4-anilinoquinazoline. Vandetanib selectively inhibits the tyrosine kinase activity of vascular endothelial growth factor receptor 2 (VEGFR2), thereby blocking VEGF-stimulated endothelial cell proliferation and migration and reducing tumor vessel permeability. This agent also blocks the tyrosine kinase activity of epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that mediates tumor cell proliferation and migration and angiogenesis.. erlotinib defined as following: A quinazoline derivative with antineoplastic properties. Competing with adenosine triphosphate, erlotinib reversibly binds to the intracellular catalytic domain of epidermal growth factor receptor (EGFR) tyrosine kinase, thereby reversibly inhibiting EGFR phosphorylation and blocking the signal transduction events and tumorigenic effects associated with EGFR activation.. bevacizumab defined as following: An anti-VEGF humanized murine monoclonal antibody. It inhibits VEGF RECEPTORS and helps to prevent PATHOLOGIC ANGIOGENESIS.. cetuximab defined as following: A chimeric monoclonal antibody that functions as an ANTINEOPLASTIC AGENT through its binding to the EPIDERMAL GROWTH FACTOR RECEPTOR, where it prevents the binding and signaling action of cell growth and survival factors.. trametinib defined as following: An orally bioavailable inhibitor of mitogen-activated protein kinase kinase (MAP2K; MAPK/ERK kinase; MEK) 1 and 2, with potential antineoplastic activity. Upon oral administration, trametinib specifically binds to and inhibits MEK 1 and 2, resulting in an inhibition of growth factor-mediated cell signaling and cellular proliferation in various cancers. MEK 1 and 2, dual specificity serine/threonine and tyrosine kinases often upregulated in various cancer cell types, play a key role in the activation of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth.. panitumumab defined as following: A human IgG2kappa monoclonal antibody specific for the epidermal growth factor receptor (EGFR). Monoclonal antibody E7.6.3 binds to the EGFR, blocking the binding of epidermal growth factor and transforming growth factor alpha to EGFR-expressing cancer cells and ultimately inhibiting EGFR-dependent cell activation and proliferation. (NCI). KRAS defined as following: Human Oncogene K-Ras is a mutated variant of KRAS2 Gene, which encodes two alternative isoforms of monomeric p21 K-RAS protein, a monomeric GTPase involved in transmembrane signal transduction that alternates between inactive GDP-bound and active GTP-bound forms. K-Ras is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase-activating protein. Mitogen-stimulated RAS stabilizes MYC protein and enhances MYC accumulation by the RAS/RAF/MAPK pathway, which appears to inhibit the proteasome-dependent degradation of MYC. Implicated in a variety of human tumors, mutations of specific amino acids activate RAS to transform cells. KRAS is involved in malignancy much more often than is HRAS. Oncogene K-Ras disrupts normal cell function.. oxaliplatin defined as following: An organoplatinum complex in which the platinum atom is complexed with 1,2-diaminocyclohexane, and with an oxalate ligand which is displaced to yield active oxaliplatin derivatives. These derivatives form inter- and intra-strand DNA crosslinks that inhibit DNA replication and transcription. Oxaliplatin is an antineoplastic agent that is often administered with FLUOROURACIL and FOLINIC ACID in the treatment of metastatic COLORECTAL NEOPLASMS.. sorafenib defined as following: A synthetic compound targeting growth signaling and angiogenesis. Sorafenib blocks the enzyme RAF kinase, a critical component of the RAF/MEK/ERK signaling pathway that controls cell division and proliferation; in addition, sorafenib inhibits the VEGFR-2/PDGFR-beta signaling cascade, thereby blocking tumor angiogenesis.. Panitumumab defined as following: A human IgG2kappa monoclonal antibody specific for the epidermal growth factor receptor (EGFR). Monoclonal antibody E7.6.3 binds to the EGFR, blocking the binding of epidermal growth factor and transforming growth factor alpha to EGFR-expressing cancer cells and ultimately inhibiting EGFR-dependent cell activation and proliferation. (NCI).", "label": "no"} {"id": "converted_8", "sentence1": "Has Denosumab (Prolia) been approved by FDA?", "sentence2": "Denosumab is a RANK-ligand antibody that was approved by the FDA in 2010 for the prevention of skeletal fractures in patients with bone metastases from solid tumors., The authors present the imaging findings and technical report of an attempted percutaneous vertebroplasty in the only patient found to be actively under treatment with denosumab after a retrospective review of the databank of patients with pathological fractures referred to the Department Radiology of the Ohio State University for percutaneous vertebroplasty (a total sample of 20 patients) since the FDA approval of denosumab (November 2010) until June of 2013 (a 30-month period)., On the basis of this data, the FDA approved denosumab for the treatment of patients whose GCTB is unresectable, or when surgery is likely to result in severe morbidity., Denosumab (Prolia®) is a fully human monoclonal antibody for RANKL, which selectively inhibits osteoclastogenesis, being recently approved for the treatment of postmenopausal osteoporosis in women at a high or increased risk of fracture by the FDA in the United Sates and by the European Medicines Agency in Europe since June 2010., Recent phase II clinical trials with denosumab in skeletally mature adolescents over age 12 years and adults with GCTB, have shown both safety and efficacy, leading to its accelerated US FDA approval on 13 June 2013. , Zoledronic acid (ZA), an intravenously administered bisphosphonate, and Denosumab, a subcutaneously administered inhibitor of nuclear factor B ligand (RANKL), have already been approved by Food and Drug Administration (FDA) for their use in treatment of bone metastases., These results led to the approval of denosumab by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), for the prevention of SREs in adults with bone metastases from solid tumors, including breast cancer., Alendronate, risedronate, zoledronic acid, denosumab, and teriparatide are Food and Drug Administration (FDA)-approved therapeutic options. , Several of these therapies have recently been approved by the FDA to treat bone cancer pain (bisphosphonates, denosumab) and others are currently being evaluated in human clinical trials (tanezumab)., A fourth agent, denosumab (bone targeted therapy) was also recently approved by the FDA for patients with bone metastasis after showing a reduction in the occurrence of skeletal-related events. , AHRQ published an updated review in March 2012 that summarized the benefits and risks of osteoporosis medications in treatment and prevention of osteoporosis, including bisphosphonates (aledronate, risedronate, ibandronate, zoledronic acid), parathyroid hormone, teriparatide, calcitonin, estrogens (for prevention in postmenopausal women), selective estrogen receptor modulators (raloxifene), and denosumab(approved by the FDA in 2010). , Four new drugs have received U.S. Food and Drug Administration (FDA)-approval in 2010 and 2011: sipuleucel-T, an immunotherapeutic agent; cabazitaxel, a novel microtubule inhibitor; abiraterone acetate, a new androgen biosynthesis inhibitor; and denosumab, a bone-targeting agent. , Recently, the US FDA and the EMA approved denosumab (a fully human monoclonal antibody) to treat skeletal-related events in bone-metastatic prostate cancer., In addition to these new and emerging therapeutic agents, denosumab was approved for the prevention of skeletal complications in patients with bone metastases due to solid tumor malignancies, providing an alternative to zoledronic acid. , Recently, denosumab was FDA-approved for prevention of SREs in patients with bone metastases from solid tumors. , In the 2010s to date, an additional 3 antibodies (denosumab, belimumab, ipilimumab) have been approved and one antibody-drug conjugate (brentuximab vedotin) is undergoing regulatory review and may be approved in the US by August 30, 2011., We also review the evidence supporting the FDA's approval of denosumab (bone-targeted therapy) as a treatment option for men with CRPC and bony metastases. , It has been approved for clinical use by the FDA in the US and by the European Medicines Agency in Europe since June 2010 (trade name Prolia(™), Amgen, Thousand Oaks, CA, USA). , The fully human monoclonal antibody denosumab (Prolia(®)) has been recently approved by the European Medical Agency (EMEA) and the Food and Drug Administration (FDA) for the treatment of postmenopausal osteoporosis. , Raloxifene and denosumab are only FDA approved for postmenopausal osteoporosis., The new antiresorptive drug, denosumab, although FDA-approved only for postmenopausal women, has been shown in a study of men on ADT to increase bone density in spine, hip, and forearm and decrease vertebral fractures on x-ray. , Since then, an additional six human mAbs have received FDA approval: panitumumab, golimumab, canakinumab, ustekinumab, ofatumumab and denosumab. [SEP]Relations: Denosumab has relations: drug_drug with Erenumab, drug_drug with Erenumab, drug_drug with Avelumab, drug_drug with Avelumab, drug_drug with Fasinumab, drug_drug with Fasinumab, drug_drug with Siponimod, drug_drug with Siponimod, drug_drug with Conatumumab, drug_drug with Conatumumab. Definitions: sipuleucel-T defined as following: A cell-based vaccine composed of autologous antigen-presenting peripheral blood mononuclear cells (enriched for a dendritic cell fraction) that have been exposed to a recombinant protein consisting of granulocyte-macrophage colony-stimulating factor (GM-CSF) fused to prostatic-acid phosphatase (PAP), a protein expressed by prostate cancer cells. Upon administration, the vaccine may stimulate an antitumor T-cell response against tumor cells expressing PAP. (NCI05). zoledronic acid defined as following: A synthetic imidazole bisphosphonate analog of pyrophosphate with anti-bone-resorption activity. A third-generation bisphosphonate, zoledronic acid binds to hydroxyapatite crystals in the bone matrix, slowing their dissolution and inhibiting the formation and aggregation of these crystals. This agent also inhibits farnesyl pyrophosphate synthase, an enzyme involved in terpenoid biosynthesis. Inhibition of this enzyme prevents the biosynthesis of isoprenoid lipids, donor substrates of farnesylation and geranylgeranylation during the post-translational modification of small GTPase signalling proteins, which are important in the process of osteoclast turnover. Decreased bone turnover and stabilization of the bone matrix contribute to the analgesic effect of zoledronic acid with respect to painful osteoblastic lesions. The agent also reduces serum calcium concentrations associated with hypercalcemia.. RANKL defined as following: Human TNFSF11 wild-type allele is located within 13q14 and is approximately 45 kb in length. This allele, which encodes tumor necrosis factor ligand superfamily member 11 protein, plays a role in osteoclast differentiation and activation. This allele also is involved in apoptotic signal transduction and regulation.. belimumab defined as following: A fully human IgG1 monoclonal antibody directed against B-Lymphocyte stimulator protein (BlyS or TNFSF13B) with potential immunomodulating activity. Belimumab specifically recognizes and inhibits the biological activity of BlyS, thereby preventing the binding of BlyS to B-lymphocytes. This inhibits the maturation of B-lymphocytes and may induce apoptosis in B-lymphocytes. In addition, it may decrease B-lymphocyte proliferation and/or survival. BlyS, a member of TNF family supporting B-lymphocyte maturation and survival, has been implicated in the pathogenesis of autoimmune diseases and B-lymphocyte malignancies.. Denosumab defined as following: A fully human monoclonal antibody directed against the receptor activator of nuclear factor kappa beta ligand (RANKL) with antiosteoclast activity. Denosumab specifically binds to RANKL and blocks the interaction of RANKL with RANK, a receptor located on osteoclast cell surfaces, resulting in inhibition of osteoclast activity, a decrease in bone resorption, and a potential increase in bone mineral density. RANKL, a protein expressed by osteoblastic cells, plays an important role in osteoclastic differentiation and activation.. calcitonin defined as following: Calcitonin (32 aa, ~3 kDa) is encoded by the human CALCA gene. This protein is involved in the modulation of blood calcium and phosphate concentrations through promoting incorporation of these ions into bone.. ipilimumab defined as following: A recombinant human immunoglobulin (Ig) G1 monoclonal antibody directed against the human T-cell receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), with immune checkpoint inhibitory and antineoplastic activities. Ipilimumab binds to CTLA4 expressed on T-cells and inhibits the CTLA4-mediated downregulation of T-cell activation. This leads to a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. CTLA4, an inhibitory receptor and member of the immunoglobulin superfamily, plays a key role in the downregulation of the immune system.. spine defined as following: The spinal or vertebral column.. Alendronate defined as following: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis.. tanezumab defined as following: A humanized monoclonal antibody directed against nerve growth factor (NGF), a modulator of nociceptor function, with potential analgesic activity. Tanezumab binds to NGF and prevents NGF binding to its high affinity, membrane-bound, catalytic receptor tropomyosin-related kinase A (TrkA), which is present on sympathetic and sensory neurons; reduced stimulation of TrkA by NGF inhibits the pain-transmission activities of these neurons. NGF, a neurotrophin, is critical to the growth and maintenance of sympathetic and sensory neurons. In addition, NGF may induce mast cells to release inflammatory proteins and may induce the upregulation of substance P and other pain-related peptides in sympathetic and sensory neurons. Upon neurotrophin binding, TrkA phosphorylates itself and members of the MAPK pathway, mediating the multiple neuronal effects of NGF.. golimumab defined as following: A human monoclonal antibody directed against the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a) with immunosuppressive activity. Golimumab binds to TNF-a, thereby preventing TNF-a-mediated immune responses. TNF-a production is dysregulated in various auto-immune diseases and in cancer.. teriparatide defined as following: A polypeptide that consists of the 1-34 amino-acid fragment of human PARATHYROID HORMONE, the biologically active N-terminal region. The acetate form is given by intravenous infusion in the differential diagnosis of HYPOPARATHYROIDISM and PSEUDOHYPOPARATHYROIDISM. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995). ofatumumab defined as following: A fully human, high-affinity IgG1 monoclonal antibody directed against the B cell CD20 cell surface antigen with potential antineoplastic activity. Ofatumumab binds specifically to CD20 on the surfaces of B cells, triggering complement-dependent cell lysis (CDCL) and antibody-dependent cell-mediated cytotoxicity (ADCC) of B cells overexpressing CD20. The CD20 antigen, found on over 90% of B cells, B cell lymphomas, and other B cells of lymphoid tumors of B cell origin, is a non-glycosylated cell surface phosphoprotein that acts as a calcium ion channel; it is exclusively expressed on B cells during most stages of B cell development.. canakinumab defined as following: A recombinant monoclonal antibody targeting human interleukin-1 beta (IL-1b), with anti-inflammatory and immunomodulating activities. Canakinumab binds IL-1b and prevents the binding of IL-1b to the IL-1 receptor and inhibits IL-1b-mediated signaling. This may suppress inflammatory responses mediated by IL-1b. IL-1b, a proinflammatory cytokine, plays a key role in inflammation.. panitumumab defined as following: A human IgG2kappa monoclonal antibody specific for the epidermal growth factor receptor (EGFR). Monoclonal antibody E7.6.3 binds to the EGFR, blocking the binding of epidermal growth factor and transforming growth factor alpha to EGFR-expressing cancer cells and ultimately inhibiting EGFR-dependent cell activation and proliferation. (NCI). abiraterone acetate defined as following: An orally active acetate ester form of the steroidal compound abiraterone with antiandrogen activity. Abiraterone inhibits the enzymatic activity of steroid 17alpha-monooxygenase (17alpha-hydrolase/C17,20 lyase complex), a member of the cytochrome p450 family that catalyzes the 17alpha-hydroxylation of steroid intermediates involved in testosterone synthesis. Administration of this agent may suppress testosterone production by both the testes and the adrenals to castrate-range levels.. Raloxifene defined as following: A selective benzothiophene estrogen receptor modulator (SERM). Raloxifene binds to estrogen receptors (ER) as a mixed estrogen agonist/antagonist; it displays both an ER-alpha-selective partial agonist/antagonist effect and a pure ER-beta-selective antagonist effect. This agent functions as an estrogen agonist in some tissues (bones, lipid metabolism) and as an estrogen antagonist in others (endometrium and breasts), with the potential for producing some of estrogen's beneficial effects without producing its adverse effects. (NCI04). breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. brentuximab vedotin defined as following: An antibody-drug conjugate (ADC) directed against the tumor necrosis factor (TNF) receptor CD30 with potential antineoplastic activity. Brentuximab vedotin is generated by conjugating the chimeric anti-CD30 monoclonal antibody SGN-30 to the cytotoxic agent monomethyl auristatin E (MMAE) via a valine-citrulline peptide linker. Upon administration and internalization by CD30-positive tumor cells, brentuximab vedotin undergoes enzymatic cleavage, releasing MMAE into the cytosol; MMAE binds to tubulin and inhibits tubulin polymerization, which may result in G2/M phase arrest and tumor cell apoptosis. Transiently activated during lymphocyte activation, CD30 (tumor necrosis factor receptor superfamily, member 8;TNFRSF8) may be constitutively expressed in hematologic malignancies including Hodgkin lymphoma and some T-cell non-Hodgkin lymphomas. The linkage system in brentuximab vedotin is highly stable in plasma, resulting in cytotoxic specificity for CD30-positive cells.. ZA defined as following: A Chinese person from the Zang (including Amdowa, Khampa and some Pumi speakers) ethnic group.. EMA defined as following: An autosomal recessive disorder of fatty acid oxidation, and branched chain amino acids (AMINO ACIDS, BRANCHED-CHAIN); LYSINE; and CHOLINE catabolism, that is due to defects in either subunit of ELECTRON TRANSFER FLAVOPROTEIN or its dehydrogenase, electron transfer flavoprotein-ubiquinone oxidoreductase (EC 1.5.5.1).. fracture defined as following: A traumatic injury to the bone in which the continuity of the bone is broken.. solid tumors defined as following: A benign or malignant neoplasm arising from tissues that do not include fluid areas. Representative examples include epithelial neoplasms (e.g. lung carcinoma, prostate carcinoma, breast carcinoma, colon carcinoma), and neoplasms arising from the soft tissues and bones (e.g. leiomyosarcoma, liposarcoma, chondrosarcoma, osteosarcoma). Neoplasms originating from the blood or bone marrow (leukemias and myeloproliferative disorders) are not considered solid tumors.. human defined as following: Members of the species Homo sapiens.. ADT defined as following: A protein complex that possesses glutamyl-tRNA(Gln) amidotransferase activity, and therefore creates Gln-tRNA by amidating Glu-tRNA; usually composed of 3 subunits: A, B, and C. Note that the C subunit may not be required in all organisms. [GOC:mlg].", "label": "yes"} {"id": "converted_3176", "sentence1": "Can mitochondria pass through membrane nanotubes?", "sentence2": "Membrane nanotubes (MNTs) act as \"highways\" between cells to facilitate the transfer of multiple signals and play an important role in many diseases. Our previous work reported on the transfer of mitochondria via MNTs between cardiomyocytes (CMs) and cardiac myofibroblasts (MFs), Membrane nanotubes play important functional roles in numerous cell activities such as cellular transport and communication.[SEP]Relations: mitochondrion has relations: cellcomp_protein with POR, cellcomp_protein with POR, cellcomp_protein with SLIT3, cellcomp_protein with SLIT3, cellcomp_protein with BID, cellcomp_protein with BID, cellcomp_protein with TRAP1, cellcomp_protein with TRAP1, cellcomp_protein with PSMB4, cellcomp_protein with PSMB4. Definitions: MFs defined as following: An autosomal dominant disorder of CONNECTIVE TISSUE with abnormal features in the heart, the eye, and the skeleton. Cardiovascular manifestations include MITRAL VALVE PROLAPSE; AORTIC ANEURYSM; and AORTIC DISSECTION. Other features include lens displacement (ectopia lentis), disproportioned long limbs and enlarged DURA MATER (dural ectasia). Marfan syndrome (type 1) is associated with mutations in the gene encoding FIBRILLIN-1 (FBN1), a major element of extracellular microfibrils of connective tissue. Mutations in the gene encoding TYPE II TGF-BETA RECEPTOR (TGFBR2) are associated with Marfan syndrome type 2.. mitochondria defined as following: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed). CMs defined as following: A heterogeneous group of disorders characterized by a congenital defect in neuromuscular transmission at the NEUROMUSCULAR JUNCTION. This includes presynaptic, synaptic, and postsynaptic disorders (that are not of autoimmune origin). The majority of these diseases are caused by mutations of various subunits of the nicotinic acetylcholine receptor (RECEPTORS, NICOTINIC) on the postsynaptic surface of the junction. (From Arch Neurol 1999 Feb;56(2):163-7). cardiomyocytes defined as following: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary..", "label": "yes"} {"id": "converted_38", "sentence1": "Does physical activity influence gut hormones?", "sentence2": "Increases in blood PYY(3-36) levels were dependent on the exercise intensity (effect of session: P<0.001 by two-way ANOVA), whereas those in GLP-1 levels were similar between two different exercise sessions., A decrease in serum leptin levels (-48.4%, p < 0.001) was observed after intervention without changes in total peptide YY and insulin levels., ur data suggest that the control of spontaneous physical activity by gut hormones or their neuropeptide targets may represent an important mechanistic component of energy balance regulation, Hunger and gut hormones remained unchanged during the bed rest., weight-bearing exercise has a greater exercise-induced appetite suppressive effect compared with non-weight-bearing exercise, and both forms of exercise lowered acylated ghrelin and increased total PYY, but the changes did not differ significantly between exercise modes., Appetite (P < 0.0005) and acylated ghrelin (P < 0.002) were suppressed during exercise but more so during SIE. Peptide YY increased during exercise but most consistently during END (P < 0.05). Acylated ghrelin was lowest in the afternoon of SIE (P = 0.018) despite elevated appetite, Following the pre-exercise meal, ghrelin was suppressed ~17% and insulin and PYY were elevated ~157 and ~40%, respectively, relative to fasting (day 7). Following exercise, PYY, ghrelin, and GH were significantly (p < 0.0001) increased by ~11, ~16 and ~813%, respectively. The noted disruption in the typical inverse relationship between ghrelin and PYY following exercise suggests that interaction of these peptides may be at least partially responsible for post-exercise appetite suppression, Plasma levels of PYY and GLP-1 were increased by exercise, whereas plasma ghrelin levels were unaffected by exercise, These findings suggest ghrelin and PYY may regulate appetite during and after exercise,, significant (P < 0.05) interaction effects for hunger, acylated ghrelin, and PYY, indicating suppressed hunger and acylated ghrelin during aerobic and resistance exercise and increased PYY during aerobic exercise, 'exercise-induced anorexia' may potentially be linked to increased PYY, GLP-1 and PP levels., Hunger scores and PYY, GLP-1 and PP levels showed an inverse temporal pattern during the 1-h exercise/control intervention, Exercise significantly increased mean PYY, GLP-1 and PP levels, and this effect was maintained during the post-exercise period for GLP-1 and PP. No significant effect of exercise was observed on postprandial levels of ghrelin, following blood donation the strenuous exercise resulted in a marked reduction in the plasma leptin, We conclude that strenuous physical exercise; 1) fails to affect plasma leptin level but when performed after meal but not after blood withdrawal it results in an increase and fall in plasma leptin, and 2) the release of gut hormones (gastrin, CCK and PP) and stress hormones (norepinephrine, cortisol, GH) increase immediately after exercise independently of feeding or blood donation, the unrestricted exercise group has a significantly elevated SRIF-LI concentration, Exercise has recently been reported to influence ghrelin and PYY concentrations.[SEP]Relations: Norepinephrine has relations: drug_effect with Aggressive behavior, drug_effect with Aggressive behavior, drug_effect with Lactic acidosis, drug_effect with Lactic acidosis, drug_effect with Anxiety, drug_effect with Anxiety. Hydrocortisone has relations: drug_effect with Increased body weight, drug_effect with Increased body weight, drug_effect with Emotional lability, drug_effect with Emotional lability. Definitions: GLP-1 defined as following: A peptide of 36 or 37 amino acids that is derived from PROGLUCAGON and mainly produced by the INTESTINAL L CELLS. GLP-1(1-37 or 1-36) is further N-terminally truncated resulting in GLP-1(7-37) or GLP-1-(7-36) which can be amidated. These GLP-1 peptides are known to enhance glucose-dependent INSULIN release, suppress GLUCAGON release and gastric emptying, lower BLOOD GLUCOSE, and reduce food intake.. leptin defined as following: A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.. peptides defined as following: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.. PYY defined as following: Peptide YY (97 aa, ~11 kDa) is encoded by the human PYY gene. This protein is involved in hormone signaling to regulate gastrointestinal processes.. insulin defined as following: A synthetic or animal-derived form of insulin used in the treatment of diabetes mellitus. Therapeutic insulin is formulated to be short-, intermediate- and long-acting in order to individualize an insulin regimen according to individual differences in glucose and insulin metabolism. Therapeutic insulin may be derived from porcine, bovine or recombinant sources. Endogenous human insulin, a pancreatic hormone composed of two polypeptide chains, is important for the normal metabolism of carbohydrates, proteins and fats and has anabolic effects on many types of tissues.. GH defined as following: A 191-amino acid polypeptide hormone secreted by the human adenohypophysis (PITUITARY GLAND, ANTERIOR), also known as GH or somatotropin. Synthetic growth hormone, termed somatropin, has replaced the natural form in therapeutic usage such as treatment of dwarfism in children with growth hormone deficiency.. CCK defined as following: Cholecystokinin (115 aa, ~13 kDa) is encoded by the human CCK gene. This protein is involved in both pancreatic enzyme release and gallbladder contraction.. appetite defined as following: Natural recurring desire for food. Alterations may be induced by APPETITE DEPRESSANTS or APPETITE STIMULANTS.. gastrin defined as following: Gastrin (101 aa, ~11 kDa) is encoded by the human GAST gene. This protein plays a role in the modulation of food digestion by the gastrointestinal system.. cortisol defined as following: The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.. PP defined as following: A 36-amino acid pancreatic hormone that is secreted mainly by endocrine cells found at the periphery of the ISLETS OF LANGERHANS and adjacent to cells containing SOMATOSTATIN and GLUCAGON. Pancreatic polypeptide (PP), when administered peripherally, can suppress gastric secretion, gastric emptying, pancreatic enzyme secretion, and appetite. A lack of pancreatic polypeptide (PP) has been associated with OBESITY in rats and mice..", "label": "yes"} {"id": "converted_1968", "sentence1": "Is infertility characteristic of individuals with Fanconi anemia?", "sentence2": "PALB2 links BRCA1 and BRCA2 in homologous recombinational repair of DNA double strand breaks (DSBs). Mono-allelic mutations in PALB2 increase the risk of breast, pancreatic, and other cancers, and biallelic mutations cause Fanconi anemia (FA). , Moreover, mutant males showed reduced fertility due to impaired meiosis and increased apoptosis in germ cells. Interestingly, mutant meiocytes showed a significant defect in sex chromosome synapsis, which likely contributed to the germ cell loss and fertility defect., In females with Fanconi anemia (FA), infertility is often accompanied by diminished ovarian reserve and hypergonadotropic amenorrhea before the age of 30 years, suggesting primary ovarian insufficiency (POI)., Substantially reduced AMH levels in females with FA suggest a primary ovarian defect associated with reduced fertility. Measurement of AMH at the time of FA diagnosis and subsequent monitoring of AMH levels at regular intervals may be useful for the timely management of complications related to POI such as subfertility/infertility, osteoporosis, and menopausal symptoms., Fanconi anemia (FA) is a human disease of bone marrow failure, leukemia, squamous cell carcinoma, and developmental anomalies, including hypogonadism and infertility. , Reduced fertility is one clinical manifestation among other well known Fanconi anemia features. , Fanconi anemia (FA) is a human disease of bone marrow failure, leukemia, squamous cell carcinoma, and developmental anomalies, including hypogonadism and infertility, Targeted disruption of exons 1 to 6 of the Fanconi Anemia group A gene leads to growth retardation, strain-specific microphthalmia, meiotic defects and primordial germ cell hypoplasia., Fanconi anemia (FA) is a human disease of bone marrow failure, leukemia, squamous cell carcinoma, and developmental anomalies, including hypogonadism and infertility., To potentially reduce late effects of malignancy, chronic graft-versus-host disease (GVHD), endocrinopathy, and infertility in patients with Fanconi anemia (FA) undergoing HLA-matched related donor hematopoietic cell transplantation (HCT), we developed a regimen using fludarabine (FLU), cyclophosphamide (CY), and anti-thymocyte globulin (ATG) followed by infusion of T-cell depleted (TCD) bone marrow (BM) or unmanipulated umbilical cord blood (UCB)., Mutations in Fanca account for the majority of cases of Fanconi anemia (FA), a recessively inherited disease identified by congenital defects, bone marrow failure, infertility, and cancer susceptibility., FANCA is mutated in more than 60% of cases of Fanconi anemia (FA), a rare genetically heterogeneous autosomal recessive disorder characterized by bone marrow failure, endocrine tissue cancer susceptibility, and infertility., In females with Fanconi anemia (FA), infertility is often accompanied by diminished ovarian reserve and hypergonadotropic amenorrhea before the age of 30 years, suggesting primary ovarian insufficiency (POI)., Fanconi anemia (FA) is a complex cancer susceptibility disorder associated with DNA repair defects and infertility, yet the precise function of the FA proteins in genome maintenance remains unclear., Fanconi anemia (FA) is a genetic disease resulting in bone marrow failure, high cancer risks, and infertility, and developmental anomalies including microphthalmia, microcephaly, hypoplastic radius and thumb.[SEP]Relations: Fanconi anemia complementation group has relations: disease_phenotype_positive with Male infertility, disease_phenotype_positive with Male infertility, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_phenotype_positive with Abnormal heart morphology, disease_phenotype_positive with Abnormal heart morphology, disease_phenotype_positive with Abnormal renal morphology, disease_phenotype_positive with Abnormal renal morphology, disease_phenotype_positive with Abnormal facial shape, disease_phenotype_positive with Abnormal facial shape. Definitions: FANCA defined as following: Fanconi anemia caused by mutations of the FANCA gene. FANCA gene mutations are the most common cause of Fanconi anemia. This gene provides instructions for making a protein that is involved in the Fanconi anemia (FA) pathway.. cancer defined as following: A malignant tumor at the original site of growth.. BRCA2 defined as following: Breast cancer type 2 susceptibility protein (3418 aa, ~384 kDa) is encoded by the human BRCA2 gene. This protein plays a role in both cell cycle regulation and DNA repair.. breast defined as following: In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.. pancreatic defined as following: Peptide hormones secreted into the blood by cells in the ISLETS OF LANGERHANS of the pancreas. The alpha cells secrete glucagon; the beta cells secrete insulin; the delta cells secrete somatostatin; and the PP cells secrete pancreatic polypeptide.. ATG defined as following: Purified gamma globulin, with immunosuppressive activity. Obtained from animals that have been immunized with human thymocytes, antithymocyte globulin (ATG) specifically recognizes and destroys T lymphocytes. Although not completely understood, the mechanism of action appears to involve T lymphocyte clearance from the circulation and modulation of T lymphocyte activity. Administering ATG with chemotherapy prior to stem cell transplantation may reduce the risk of graft-versus-host (GVH) disease.. microphthalmia defined as following: Congenital or developmental anomaly in which the eyeballs are abnormally small.. FLU defined as following: Human ZMYND10 wild-type allele is located in the vicinity of 3p21.3 and is approximately 6 kb in length. This allele, which encodes zinc finger MYND domain-containing protein 10, is involved in motile ciliary function. Mutations in this gene are associated with primary ciliary dyskinesia-22.. leukemia defined as following: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006). cyclophosphamide defined as following: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.. fludarabine defined as following: A fluorinated nucleotide antimetabolite analog of the antiviral agent vidarabine (ara-A) with antineoplastic activity. Administered parenterally as a phosphate salt, fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite may inhibit DNA polymerase alpha, ribonucleotide reductase and DNA primase, thereby interrupting DNA synthesis and inhibiting tumor cell growth. (NCI04). T-cell defined as following: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. chronic graft-versus-host disease defined as following: Late chronic graft versus host disease is defined as presence of symptoms and signs 100 days after an allogenic transplant.. microcephaly defined as following: Head circumference below 2 standard deviations below the mean for age and gender. [PMID:15806441, PMID:19125436, PMID:25465325, PMID:9683597]. endocrinopathy defined as following: A non-neoplastic or neoplastic disorder that affects the endocrine system. Representative examples of non-neoplastic disorders include diabetes mellitus, hyperthyroidism, and adrenal gland insufficiency. Representative examples of neoplastic disorders include carcinoid tumor, neuroendocrine carcinoma, and pheochromocytoma.. BRCA1 defined as following: Breast cancer type 1 susceptibility protein (1863 aa, ~208 kDa) is encoded by the human BRCA1 gene. This protein plays a role in both the maintenance of DNA and the mediation of ubiquitin E3 ligase activity.. mutant defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. PALB2 defined as following: Partner and localizer of BRCA2 (1186 aa, ~131 kDa) is encoded by the human PALB2 gene. This protein may play roles in cell cycle checkpoints and the repair of damaged DNA resolved by recombination.. GVHD defined as following: Therapy to prevent or treat graft vs host disease.. primary ovarian insufficiency defined as following: Cessation of ovarian function after MENARCHE but before the age of 40, without or with OVARIAN FOLLICLE depletion. It is characterized by the presence of OLIGOMENORRHEA or AMENORRHEA, elevated GONADOTROPINS, and low ESTRADIOL levels. It is a state of female HYPERGONADOTROPIC HYPOGONADISM. Etiologies include genetic defects, autoimmune processes, chemotherapy, radiation, and infections. The most commonly known genetic cause is the expansion of a CGG repeat to 55 to 199 copies in the 5' untranslated region in the X-linked FMR1 gene.. HCT defined as following: The volume of packed RED BLOOD CELLS in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, ANEMIA shows a low value; POLYCYTHEMIA, a high value.. hypogonadism defined as following: Condition resulting from deficient gonadal functions, such as GAMETOGENESIS and the production of GONADAL STEROID HORMONES. It is characterized by delay in GROWTH, germ cell maturation, and development of secondary sex characteristics. Hypogonadism can be due to a deficiency of GONADOTROPINS (hypogonadotropic hypogonadism) or due to primary gonadal failure (hypergonadotropic hypogonadism).. AMH defined as following: Muellerian-inhibiting factor (560 aa, ~59 kDa) is encoded by the human AMH gene. This protein plays a role in the development of the male reproductive system.. germ cells defined as following: The reproductive cells in multicellular organisms at various stages during GAMETOGENESIS.. squamous cell carcinoma defined as following: A squamous cell carcinoma (SCC) arising from the anal canal or the anal margin (perianal skin). Human papillomavirus is detected in the majority of cases. Homosexual HIV-positive men have an increased risk of developing anal squamous cell carcinoma in comparison to the general male population. Symptoms include anal pruritus, discomfort when sitting, pain, change in bowel habit, and bleeding. The prognosis is generally better for anal margin SCC than for anal canal SCC.. gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. bone marrow failure defined as following: A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat. [DDD:wouwehand, HPO:probinson]. congenital defects defined as following: Malformations of organs or body parts during development in utero.. infertility defined as following: Complete inability to conceive or induce conception.. mutated defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. Fanconi anemia defined as following: Fanconi anemia caused by mutations of the FANCA gene. FANCA gene mutations are the most common cause of Fanconi anemia. This gene provides instructions for making a protein that is involved in the Fanconi anemia (FA) pathway..", "label": "yes"} {"id": "converted_3008", "sentence1": "Can Diazepam be beneficial in the treatment of traumatic brain injury?", "sentence2": "he present experiment examined the effects of diazepam, a positive modulator at the GABA(A) receptor, on survival and cognitive performance in traumatically brain-injured animals. I[SEP]Relations: Diazepam has relations: drug_effect with Memory impairment, drug_effect with Memory impairment, drug_effect with Loss of consciousness, drug_effect with Loss of consciousness, drug_effect with Pain, drug_effect with Pain, drug_effect with Sensory impairment, drug_effect with Sensory impairment, drug_effect with Headache, drug_effect with Headache. Definitions: diazepam defined as following: A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.. GABA(A) receptor defined as following: Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.. traumatic brain injury defined as following: A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.. Diazepam defined as following: A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity..", "label": "yes"} {"id": "converted_1335", "sentence1": "Is there increased incidence of incontinence in athletes?", "sentence2": "Urinary incontinence affects women of all ages, including top female athletes, but is often under-reported. The highest prevalence of urinary incontinence is reported in those participating in high impact sports., The prevalence of female stress urinary incontinence is high, and young adults are also affected, including athletes, especially those involved in \"high-impact\" sports, Analysis of these data suggests that perineal pressure is decreased in female athletes compared with nonathlete women. A lower perineal pressure correlates with increased symptoms of urinary incontinence and pelvic floor dysfunction., Urinary incontinence is a prevalent condition among athletes that is not openly discussed., High-level sport appears to be a significant independent risk factor for AI in healthy young women. , The prevalence of LUTS was 54.7%, and 30% for urinary incontinence., LUTS and incontinence are prevalent in female athletes., A relationship between sport or fitness activities and urinary incontinence (UI) previously has been described in women. , studies have also shown a high prevalence of SUI in young, physically fit female athletes. , There was urinary incontinence in female long-distance runners and a correlation with eating disorders., young female athletes participating in high-impact sports may be at higher risk for urinary incontinence., Results indicated that more than 25% of those completing surveys experienced incontinence and that more than 90% had never told anyone about their problem and had no knowledge of preventive measures; 16% reported incontinence negatively impacted their quality of life., There is a very high prevalence of urinary incontinence in women athletes., Women athletes should be counseled about the increased risk of urinary incontinence with ultra high-impact sports and eating disorders., Stress urinary incontinence is a barrier to women's participation in sport and fitness activities and, therefore, it may be a threat to women's health, self-esteem and well-being. The prevalence during sports among young, nulliparous elite athletes varies between 0% (golf) and 80% (trampolinists). The highest prevalence is found in sports involving high impact activities such as gymnastics, track and field, and some ball games, Urinary leakage is common among elite athletes and dancers, particularly during training, but also during daily life activities., There is a high prevalence of stress and urge incontinence in female elite athletes. The frequency of SUI and urge incontinence was significantly higher in eating disordered athletes compared with healthy athletes., High impact sports activities may produce urinary incontinence., Urinary incontinence during physical stresses is common in young nulliparous wome, Incontinence during physical stresses is common in young, highly fit, nulliparous women.[SEP]Relations: Urinary incontinence has relations: drug_effect with Lenalidomide, drug_effect with Lenalidomide, drug_effect with Cyclosporine, drug_effect with Cyclosporine, drug_effect with Ibuprofen, drug_effect with Ibuprofen, drug_effect with Urofollitropin, drug_effect with Urofollitropin, drug_effect with Felbamate, drug_effect with Felbamate. Definitions: urinary incontinence defined as following: Involuntary loss of URINE, such as leaking of urine. It is a symptom of various underlying pathological processes. Major types of incontinence include URINARY URGE INCONTINENCE and URINARY STRESS INCONTINENCE.. eating disorders defined as following: A broad group of psychological disorders with abnormal eating behaviors leading to physiological effects from overeating or insufficient food intake.. Urinary defined as following: The duct which coveys URINE from the pelvis of the KIDNEY through the URETERS, BLADDER, and URETHRA.. Stress urinary incontinence defined as following: Involuntary discharge of URINE as a result of physical activities that increase abdominal pressure on the URINARY BLADDER without detrusor contraction or overdistended bladder. The subtypes are classified by the degree of leakage, descent and opening of the bladder neck and URETHRA without bladder contraction, and sphincter deficiency.. AI defined as following: Pathological condition characterized by the backflow of blood from the ASCENDING AORTA back into the LEFT VENTRICLE, leading to regurgitation. It is caused by diseases of the AORTIC VALVE or its surrounding tissue (aortic root).. incontinence defined as following: Involuntary passage of stool or urine from the body..", "label": "yes"} {"id": "converted_3835", "sentence1": "Do exon 38 or 39 KMT2D missense variants cause Kabuki syndrome type 1 (KS1)?", "sentence2": "A restricted spectrum of missense KMT2D variants cause a multiple malformations disorder distinct from Kabuki syndrome., To investigate if specific exon 38 or 39 KMT2D missense variants (MVs) cause a condition distinct from Kabuki syndrome type 1 (KS1).METHODS: Multiple individuals, with MVs in exons 38 or 39 of KMT2D that encode a highly conserved region of 54 amino acids flanked by Val3527 and Lys3583, were identified and phenotyped. Functional tests were performed to study their pathogenicity and understand the disease mechanism.RESULTS: The consistent clinical features of the affected individuals, from seven unrelated families, included choanal atresia, athelia or hypoplastic nipples, branchial sinus abnormalities, neck pits, lacrimal duct anomalies, hearing loss, external ear malformations, and thyroid abnormalities. None of the individuals had intellectual disability. The frequency of clinical features, objective software-based facial analysis metrics, and genome-wide peripheral blood DNA methylation patterns in these patients were significantly different from that of KS1. Circular dichroism spectroscopy indicated that these MVs perturb KMT2D secondary structure through an increased disordered to ɑ-helical transition.CONCLUSION: KMT2D MVs located in a specific region spanning exons 38 and 39 and affecting highly conserved residues cause a novel multiple malformations syndrome distinct from KS1. Unlike KMT2D haploinsufficiency in KS1, these MVs likely result in disease through a dominant negative mechanism.[SEP]Relations: Kabuki syndrome has relations: disease_protein with KMT2D, disease_protein with KMT2D, disease_protein with KDM6A, disease_protein with KDM6A, disease_phenotype_positive with Generalized hypotonia, disease_phenotype_positive with Generalized hypotonia, disease_protein with RAP1B, disease_protein with RAP1B, disease_protein with RAP1A, disease_protein with RAP1A. Definitions: athelia defined as following: Absence of one or both mammary glands.. KS1 defined as following: This gene is involved in cellular homeostasis and chemotaxis.. MVs defined as following: A SI derived unit of electric potential and electromotive force that is equal to one million volts.. hearing loss defined as following: Partial or complete loss of the ability to detect or understand sounds resulting from damage to the outer, middle, or inner ear structures. Causes include exposure to loud noise, ear infections, injuries to the ear, genetic, and congenital disorders.. KMT2D defined as following: Histone-lysine N-methyltransferase MLL2 (5262 aa, ~564 kDa) is a transcriptional regulatory protein that is encoded by the human MLL2 gene and has a role in epigenetic transcriptional activation.. thyroid abnormalities defined as following: Pathological processes involving the THYROID GLAND.. exons defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. choanal atresia defined as following: A congenital abnormality that is characterized by a blocked CHOANAE, the opening between the nose and the NASOPHARYNX. Blockage can be unilateral or bilateral; bony or membranous.. intellectual disability defined as following: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28). exon defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA..", "label": "no"} {"id": "converted_2881", "sentence1": "Is collagen the most abundant human protein?", "sentence2": "As the most abundant protein in the body, collagen is essential to maintain the normal structure and strength of connective tissue, such as bones, skin, cartilage, and blood vessels., Collagen is the most abundant protein family in mammals., Collagen is a fibrillar protein that conforms the conjunctive and connective tissues in the human body, essentially skin, joints, and bones. This molecule is one of the most abundant in many of the living organisms due to its connective role in biological structures.[SEP]Relations: connective tissue has relations: anatomy_protein_present with COL3A1, anatomy_protein_present with COL3A1, anatomy_protein_present with COL1A1, anatomy_protein_present with COL1A1, anatomy_protein_present with GNS, anatomy_protein_present with GNS, anatomy_protein_present with GLMN, anatomy_protein_present with GLMN, anatomy_protein_present with BEST2, anatomy_protein_present with BEST2. Definitions: Collagen defined as following: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).. mammals defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. molecule defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. human body defined as following: Anatomical structure which is the aggregate material substance of an individual member of a species.. connective tissues defined as following: Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX.. cartilage defined as following: A non-vascular form of connective tissue composed of CHONDROCYTES embedded in a matrix that includes CHONDROITIN SULFATE and various types of FIBRILLAR COLLAGEN. There are three major types: HYALINE CARTILAGE; FIBROCARTILAGE; and ELASTIC CARTILAGE.. protein family defined as following: Collection of proteins that are evolutionarily related. This is reflected in the structural and functional similarities as well as in the extent of sequence conservation or residue identity. (from SCOP). collagen defined as following: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH)..", "label": "yes"} {"id": "converted_391", "sentence1": "Does the majority of the mitochondrial genomes abide to the second parity rule (PR2)?", "sentence2": "a large number of mitochondrial genomes significantly deviate from the 2nd parity rule in contrast to the eubacterial ones, mitochondria may be divided into three distinct sub-groups according to their overall deviation from the aforementioned parity rule., The behaviour of the large majority of the mitochondrial genomes may be attributed to their distinct mode of replication, which is fundamentally different from the one of the eubacteria., We tested all available organellar genomes and found that a large number of mitochondrial genomes significantly deviate from the 2nd parity rule in contrast to the eubacterial ones, although mitochondria are believed to have evolved from proteobacteria., The behaviour of the large majority of the mitochondrial genomes may be attributed to their distinct mode of replication, which is fundamentally different from the one of the eubacteria., We tested all available organellar genomes and found that a large number of mitochondrial genomes significantly deviate from the 2nd parity rule in contrast to the eubacterial ones, although mitochondria are believed to have evolved from proteobacteria., The behaviour of the large majority of the mitochondrial genomes may be attributed to their distinct mode of replication, which is fundamentally different from the one of the eubacteria, We tested all available organellar genomes and found that a large number of mitochondrial genomes significantly deviate from the 2nd parity rule in contrast to the eubacterial ones, although mitochondria are believed to have evolved from proteobacteria[SEP]Relations: mitochondrion has relations: cellcomp_protein with PARS2, cellcomp_protein with PARS2, cellcomp_protein with RARS2, cellcomp_protein with RARS2. mitochondrial genome maintenance has relations: bioprocess_protein with MGME1, bioprocess_protein with MGME1, bioprocess_protein with AKT3, bioprocess_protein with AKT3, bioprocess_protein with PIF1, bioprocess_protein with PIF1. Definitions: mitochondria defined as following: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed). eubacteria defined as following: A genus of gram-positive, rod-shaped bacteria found in cavities of man and animals, animal and plant products, infections of soft tissue, and soil. Some species may be pathogenic. No endospores are produced. The genus Eubacterium should not be confused with EUBACTERIA, one of the three domains of life.. mitochondrial genomes defined as following: The genetic complement of MITOCHONDRIA as represented in their DNA..", "label": "no"} {"id": "converted_2117", "sentence1": "Is Lennox-Gastaut Syndrome usually diagnosed in older adults?", "sentence2": "We studied 15 LGS patients (mean age ± 1 standard deviation [SD] = 28.7 ± 10.6 years) and 17 healthy controls (mean age ± 1 SD = 27.6 ± 6.6 years), children with Lennox-Gastaut syndrome, Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by mixed seizures, cognitive decline, and generalized slow (<3 Hz) spike wave discharges on electroencephalography, Clinical course and results of therapy were analysed in the group of 92 children, aged between 3 and 9 years, with diagnosed Lennox-Gastaut syndrome., We report the case of a 27-year-old man with a neurodevelopmental syndrome due to a 15q duplication, with intellectual disability, psychiatric disturbances, and an epileptic phenotype diagnosed as late-onset Lennox-Gastaut syndrome., Lennox-Gastaut syndrome is a relatively rare epilepsy syndrome that usually begins in early-mid childhood and is characterized by multiple seizure types, particularly generalized seizures, which are often resistant to antiepileptic drug medication, Lennox-Gastaut Syndrome is a severe childhood epilepsy syndrome characterised by the diagnostic triad of a slow spike and wave pattern on electroencephalogram, multiple seizure types and developmental delay, We report the case of a 27-year-old man with a neurodevelopmental syndrome due to a 15q duplication, with intellectual disability, psychiatric disturbances, and an epileptic phenotype diagnosed as late-onset Lennox-Gastaut syndrome.., The Lennox-Gastaut syndrome, a severe form of epilepsy that usually begins in early childhood, is difficult to treat., Lennox-Gastaut syndrome is a relatively rare epilepsy syndrome that usually begins in early-mid childhood and is characterized by multiple seizure types, particularly generalized seizures, which are often resistant to antiepileptic drug medication., The Lennox-Gastaut syndrome is an age-specific disorder, characterised by epileptic seizures, a characteristic electroencephalogram (EEG), psychomotor delay and behaviour disorders. It occurs more frequently in males and onset is usually before the age of eight, with a peak between three and five years. Late cases occurring in adolescence and early adulthood have rarely been reported. [SEP]Relations: Lennox-Gastaut syndrome has relations: disease_disease with childhood-onset epilepsy syndrome, disease_disease with childhood-onset epilepsy syndrome, disease_disease with childhood electroclinical syndrome, disease_disease with childhood electroclinical syndrome, disease_disease with childhood onset epileptic encephalopathy, disease_disease with childhood onset epileptic encephalopathy, disease_disease with syndromic disease, disease_disease with syndromic disease, disease_disease with developmental and epileptic encephalopathy, disease_disease with developmental and epileptic encephalopathy. Definitions: man defined as following: Members of the species Homo sapiens.. Lennox-Gastaut Syndrome defined as following: A syndrome characterized by frequent episodes of epilepsy during childhood. The epileptic episodes may be tonic, atonic, myoclonic, or absence seizures. It may be accompanied by mental retardation and behavioral problems.. LGS defined as following: Autosomal dominant disorder characterized by cone-shaped epiphyses in the hands and multiple cartilaginous exostoses. INTELLECTUAL DISABILITY and abnormalities of chromosome 8 are often present. The exostoses in this syndrome appear identical to those of hereditary multiple exostoses (EXOSTOSES, HEREDITARY MULTIPLE).. epilepsy defined as following: A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313). cognitive decline defined as following: Loss of previously present mental abilities, generally in adults. [HPO:probinson]. epilepsy syndrome defined as following: EPILEPTIC SEIZURES that are of similar type and age of onset and have other similar features (e.g., clinical course, EEG findings, genetic association and neuropathology).. intellectual disability defined as following: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28).", "label": "no"} {"id": "converted_3379", "sentence1": "Is NicVAX vaccine effective for smoking cessation?", "sentence2": "CONCLUSION: The nicotine vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support., First efficacy results of the nicotine vaccine 3'-AmNic-rEPA (NicVAX) showed that only a subgroup of the top 30% antibody responders achieved higher abstinence rates than placebo. , FINDINGS: There was no difference in abstinence rates between NicVAX and placebo from weeks 9 to 52 [27.7 versus 30.0%, odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.62-1.29] or weeks 37 to 52 (33.8 versus 33.2%, OR = 1.03, 95% CI = 0.73-1.46). The top 30% antibody responders, compared to the placebo group, showed a non-significant tendency towards higher abstinence rates from weeks 37 to 52 (42.2 versus 33.2%, OR = 1.47, 95% CI = 0.89-2.42), Unfortunately, the only vaccine tested in two large, randomized Phase III trials, 3'-amino-methyl-nicotine r-exoprotein A conjugate vaccine (NicVAX(®), Nabi Biopharmaceuticals, MD, USA), did not demonstrate efficacy., The RR for 12 month cessation in active and placebo groups was 1.35 (95% Confidence Interval (CI) 0.82 to 2.22) in the trial of NIC002 and 1.74 (95% CI 0.73 to 4.18) in one NicVAX trial. Two Phase III NicVAX trials, for which full results were not available, reported similar quit rates of approximately 11% in both groups., AUTHORS' CONCLUSIONS: There is currently no evidence that nicotine vaccines enhance long-term smoking cessation., 3'AmNic-rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. , Recently, the most advanced candidate vaccine, NicVAX, failed to meet the primary endpoint in two large phase III studies, although the correlation of higher abstinence rates in subjects with higher immunity to nicotine was observed., CONCLUSION\n\nThe nicotine vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support., First efficacy results of the nicotine vaccine 3'-AmNic-rEPA (NicVAX) showed that only a subgroup of the top 30% antibody responders achieved higher abstinence rates than placebo., CONCLUSION The nicotine vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support., First efficacy results of the nicotine vaccine 3'-AmNic-rEPA ( NicVAX ) showed that only a subgroup of the top 30 % antibody responders achieved higher abstinence rates than placebo, First efficacy results of the nicotine vaccine 3'-AmNic-rEPA (NicVAX) showed that only a subgroup of the top 30% antibody responders achieved higher abstinence rates than placebo., FINDINGS\nThere was no difference in abstinence rates between NicVAX and placebo from weeks 9 to 52 [27.7 versus 30.0%, odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.62-1.29] or weeks 37 to 52 (33.8 versus 33.2%, OR = 1.03, 95% CI = 0.73-1.46)., CONCLUSION\nThe nicotine vaccine, NicVAX, does not appear to improve the chances of stopping smoking when given in addition to varenicline and behavioural support.[SEP]Relations: Nicotine has relations: drug_drug with Niclosamide, drug_drug with Niclosamide, drug_drug with Celecoxib, drug_drug with Celecoxib, drug_drug with Nicardipine, drug_drug with Nicardipine, drug_drug with Mefenorex, drug_drug with Mefenorex, drug_drug with Desvenlafaxine, drug_drug with Desvenlafaxine. Definitions: varenicline defined as following: A partial agonist of the nicotinic acetylcholine receptor (nAChR) subtype alpha4beta2. Nicotine stimulation of central alpha4beta2 nAChRs located at presynaptic terminals in the nucleus accumbens causes the release of the neurotransmitter dopamine, which may be associated with the experience of pleasure; nicotine addiction constitutes a physiologic dependence related to this dopaminergic reward system. As an AChR partial agonist, varenicline attenuates the craving and withdrawal symptoms that occur with abstinence from nicotine but is not habit-forming itself.. antibody defined as following: A protein complex that in its canonical form is composed of two identical immunoglobulin heavy chains and two identical immunoglobulin light chains, held together by disulfide bonds and sometimes complexed with additional proteins. An immunoglobulin complex may be embedded in the plasma membrane or present in the extracellular space, in mucosal areas or other tissues, or circulating in the blood or lymph. [GOC:add, GOC:jl, ISBN:0781765196]. nicotine defined as following: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke..", "label": "no"} {"id": "converted_4703", "sentence1": "Does sphingosine-1 phosphoate suppress epiregulin?", "sentence2": "S1P-induced FOXO1 and EREG gene expression suggests that the activation of S1P-S1PR axis may cooperate with gonadotropins in modulating follicle development., S1P-dependent CREB phosphorylation induced FOXO1 and the EGF-like epiregulin-encoding gene (EREG), confirming the exclusive role of gonadotropins and interleukins in this process, but did not affect steroidogenesis. [SEP]Relations: interleukin-8 receptor binding has relations: molfunc_protein with YARS1, molfunc_protein with YARS1, molfunc_protein with CXCL8, molfunc_protein with CXCL8. cAMP response element binding protein binding has relations: molfunc_protein with CRTC1, molfunc_protein with CRTC1, molfunc_protein with CRTC3, molfunc_protein with CRTC3, molfunc_protein with CRTC2, molfunc_protein with CRTC2. Definitions: gonadotropins defined as following: A class of formulated therapeutic analogs of the endogenous gonadotropin that stimulates or promotes the function of the gonads. Therapeutic gonadotropins are derived from animal or recombinant sources. Gonadotropins include follicle-stimulating hormone, luteinizing hormone and chorionic gonadotropin. These agents stimulate discrete cellular components of the gonads, exerting effects in both males and females. (NCI04). FOXO1 defined as following: This gene is involved in transcriptional regulation and may play a role in myogenic growth and differentiation.. EREG defined as following: Proepiregulin (169 aa, ~19 kDa) is encoded by the human EREG gene. This protein plays a role in the promotion of cell proliferation.. interleukins defined as following: Formulated therapeutic analogs of one of a number of endogenous cytokine interleukins. Produced by T cells, macrophages, and other cells, interleukins bind to a specific surface receptor on immunohematopoietic cells, thereby inducing a multitude of biologic effects including stimulation of growth, differentiation, and proliferation of lymphocytes and eosinophils; activation of lymphocytes and macrophages; enhancement of mast cell activity; activation of the acute phase response; and stimulation of hematopoiesis. Some interleukins may enhance the host's immune response to malignant cells by stimulating lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL), which are capable of lysing some tumor cells. (NCI04). CREB defined as following: Ubiquitously or widely expressed human cAMP Responsive Element Binding Proteins (bZIP/CREB Family) are conserved nuclear bZIP domain dimeric transcription factors that bind to octameric DNA palindrome cAMP-response elements (CRE) present in many viral and cellular promoters and induce gene transcription in response to cAMP signaling pathways. CREB proteins bind to DNA as a homodimer or a heterodimer with JUN/c-Jun or ATF2/CREBP1. Increased cAMP levels following stimulation activate cAMP-dependent protein kinase A, which phosphorylates CREB proteins that stimulate transcription of cAMP-responsive genes. Calcium-regulated CREB transcription factors integrate calcium and cAMP signals. cAMP pathways provide a chief means by which cellular growth, differentiation, and function can be influenced by extracellular signals. (NCI). epiregulin defined as following: This gene plays a role in cellular biogenesis, organization and proliferation..", "label": "no"} {"id": "converted_3432", "sentence1": "Is Dexmecamylamine effective for depression?", "sentence2": "At treatment end, no significant differences were seen for change in MADRS total score with TC-5214 versus placebo. Furthermore, there were no significant differences in any of the secondary endpoints. , TC-5214 (dexmecamylamine) is a nicotinic channel modulator that has previously been evaluated for treatment of major depression disorder (MDD) and is currently being evaluated by Targacept as a treatment for overactive bladder. , In these 2 flexibly-dosed studies, no specific therapeutic effects were observed for TC-5214 (1-4 mg BID) adjunct to antidepressant in the primary endpoint or any secondary endpoint; however, TC-5214 was generally well tolerated. In conclusion, no antidepressant effect of TC-5214 was observed in these studies., TC-5214 (dexmecamylamine) is a nicotinic channel modulator that has previously been evaluated for treatment of major depression disorder (MDD) and is currently being evaluated by Targacept as a treatment for overactive bladder., No notable differences were observed between dexmecamylamine and placebo for any secondary end point., TC-5214 ( dexmecamylamine ) is a nicotinic channel modulator that has previously been evaluated for treatment of major depression disorder ( MDD ) and is currently being evaluated by Targacept as a treatment for overactive bladder . , TC-5214 (dexmecamylamine) is a nicotinic channel modulator that has previously been evaluated for treatment of major depression disorder (MDD) and is currently being evaluated by Targacept as a treatment for overactive bladder., At treatment end, no significant differences were seen for change in MADRS total score with TC-5214 versus placebo., In these 2 flexibly-dosed studies, no specific therapeutic effects were observed for TC-5214 (1-4 mg BID) adjunct to antidepressant in the primary endpoint or any secondary endpoint; however, TC-5214 was generally well tolerated.[SEP]Relations: Mecamylamine has relations: drug_drug with Dexetimide, drug_drug with Dexetimide, drug_drug with Dextran, drug_drug with Dextran, drug_drug with Dextromoramide, drug_drug with Dextromoramide, drug_drug with Dexmedetomidine, drug_drug with Dexmedetomidine, drug_drug with Dexniguldipine, drug_drug with Dexniguldipine. Definitions: MDD defined as following: Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5). antidepressant defined as following: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.. BID defined as following: Two times per day, at unspecified times..", "label": "no"} {"id": "converted_1546", "sentence1": "Is Rac1 involved in cancer cell invasion?", "sentence2": "In the Matrigel invasion assay, knockdown of CCR1 and inhibition of the ERK and Rac signaling pathways significantly decreased the number of invading cells., These results demonstrated for the first time that the interaction of CCR1 with CCL5 caused by increased expression of CCR1 promotes invasion of PC3PR cells by increasing secretion of MMPs 2 and 9 and by activating ERK and Rac signaling., These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes., Activated PAR1 induced RhoA and Rac1 phosphorylation, and subsequent overexpression of myosin IIA and filamin B which are stress fiber components that were identified by PMF analysis of peptide mass data obtained by MALDI-TOF/MS measurement. , These results demonstrate that PAR1 activation induces cell morphological change associated with cell motility via Rho family activation and cytoskeletal protein overexpression, and has a critical role in gastric cancer cell invasion and metastasis., Rac1 was found to be required for actopaxin-induced matrix degradation whereas inhibition of myosin contractility promoted degradation in the phosphomutant-expressing Quint cells, indicating that a balance of Rho GTPase signaling and regulation of cellular tension are important for the process., Taken together, this study demonstrates a new role for actopaxin phosphorylation in matrix degradation and cell invasion via regulation of Rho GTPase signaling., BART inhibits pancreatic cancer cell invasion by Rac1 inactivation through direct binding to active Rac1, We report that Binder of Arl Two (BART) plays a role in inhibiting cell invasion by regulating the activity of the Rho small guanosine triphosphatase protein Rac1 in pancreatic cancer cells., BART interacts with active forms of Rac1, and the BART-Rac1 complex localizes at the leading edges of migrating cancer cells. Suppression of BART increases active Rac1, thereby increasing cell invasion. Treatment of pancreatic cancer cells in which BART is stably knocked down with a Rac1 inhibitor decreases invasiveness. Thus, BART-dependent inhibition of cell invasion is likely associated with decreased active Rac1., The Rac1 inhibitor inhibits the lamellipodia formation that is stimulated by suppression of BART., Our results imply that BART regulates actin-cytoskeleton rearrangements at membrane ruffles through modulation of the activity of Rac1, which, in turn, inhibits pancreatic cancer cell invasion., It has been reported as an important inducer of cancer cell migration and invasion, with underlying molecular mechanisms involving the signalling mediated by its juxtamembrane domain, the secretion of matrix metalloproteases to the extracellular media, and the cleavage of a P-cadherin soluble form with pro-invasive activity. Intracellularly, this protein interferes with the endogenous cadherin/catenin complex, inducing p120-catenin delocalization to the cytoplasm, and the consequent activation of Rac1/Cdc42 and associated alterations in the actin cytoskeleton., Targeted down-regulation of RhoC led to sustained activation of Rac1 GTPase and morphological, molecular and phenotypic changes reminiscent of epithelial to mesenchymal transition., We also find that Rac1 GTPase mediates tight binding of prostate cancer cells to bone marrow endothelial cells and promotes retraction of endothelial cells required for tumor cell diapedesis., Finally, Rac1 leads to β1 integrin activation, suggesting a mechanism that Rac1 can mediate tight binding with endothelial cells., Together, our data suggest that Rac1 GTPase is key mediator of prostate cancer cell-bone marrow endothelial cell interactions., Furthermore, expression of dominant-negative Rac1 (T17N) could largely block EGF-induced PI3K/Akt-PAK1 activation and cell migration., Our study demonstrated that EGF-induced cell migration involves a cascade of signalling events, including activation of Rac1, generation of ROS and subsequent activation of PI3K/Akt and PAK1., Small GTPase proteins, including RhoA, RhoB, RhoC, Rac1, and cdc42, are important molecules for linking cell shape and cell-cycle progression because of their role in both cytoskeletal arrangements and mitogenic signaling., The suppression of MMP-2 expression by CTXG led to an inhibition of SW620 cells invasion and migration by inactivating Rac1 and Cdc42 but not RhoA GTPase., In conclusion, our data demonstrate that CTXG exerted anti-invasion action in SW620 cells by targeting MMP-2 though regulating the activities of Rac1, Cdc42 and their downstream transcriptional factor AP-1., ctivation of H-Ras and Rac1 correlates with epidermal growth factor-induced invasion in Hs578T and MDA-MB-231 breast carcinoma cells, We have previously shown that H-Ras, but not N-Ras, induces an invasive phenotype mediated by small GTPase Rac1 in MCF10A human breast epithelial cells., Moreover, siRNA-knockdown of Rac1 significantly inhibited the EGF-induced invasiveness in these cells., Our data demonstrate that the activation of H-Ras and the downstream molecule Rac1 correlates with EGF-induced breast cancer cell invasion, providing important information on the regulation of malignant progression in mammary carcinoma cells., At 50% growth-inhibiting concentration, icariin significantly suppressed tumor cells migration and invasion, which were traceable to down-regulation of Rac1 and VASP. , These results indicate that icariin exerts negative effects on tumor cell invasion and migration via the Rac1-dependent VASP pathway and may be a potential anti-cancer drug., RhoGDI2 modulates the invasiveness and metastatic ability of cancer cells through regulation of Rac1 activity., We also showed that GBM cells secrete Sema3A endogenously, and RNA interference-mediated downregulation of Sema3A inhibits migration and alters cell morphology that is dependent on Rac1 activity., LMO1 and Dock180, a bipartite Rac1 guanine nucleotide exchange factor, promote human glioma cell invasion, Here, we report for the first time that engulfment and cell motility 1 (ELMO1) and dedicator of cytokinesis 1 (Dock180), a bipartite Rac1 guanine nucleotide exchange factor (GEF), are evidently linked to the invasive phenotype of glioma cells., Inhibition of endogenous ELMO1 and Dock180 expression significantly impeded glioma cell invasion in vitro and in brain tissue slices with a concomitant reduction in Rac1 activation., Members of the Rac family of small GTPases are known to act as regulators of actin cytoskeletal structures and strongly influence the cellular processes of integrin-mediated adhesion and migration. Even though hyperactivated Rac proteins have been shown to influence metastatic processes, these proteins have never been directly linked to metastatic progression. , We show that increased activation of Rac proteins directly correlates with increasing metastatic potential in a panel of cell variants derived from a single metastatic breast cancer cell line (MDA-MB-435)., Expression of a dominant active Rac1 or a dominant active Rac3 resulted in a more invasive and motile phenotype., Moreover, expression of either dominant negative Rac1 or dominant negative Rac3 into the most metastatic cell variant resulted in decreased invasive and motile properties., This study correlates endogenous Rac activity with high metastatic potential and implicates Rac in the regulation of cell migration and invasion in metastatic breast cancer cells. Taken together, these results suggest a role for both the Rac1 and Rac3 GTPases in human breast cancer progression.[SEP]Relations: cytoplasm has relations: cellcomp_protein with RAC1, cellcomp_protein with RAC1, cellcomp_protein with RAB1C, cellcomp_protein with RAB1C, cellcomp_protein with RARS1, cellcomp_protein with RARS1, cellcomp_protein with RAD51C, cellcomp_protein with RAD51C. ELMO1 has relations: protein_protein with RAC1, protein_protein with RAC1. Definitions: LMO1 defined as following: Rhombotin-1 (156 aa, ~18 kDa) is encoded by the human LMO1 gene. This protein is involved in transcriptional regulation.. prostate cancer defined as following: A primary or metastatic malignant tumor involving the prostate gland. The vast majority are carcinomas.. RhoB defined as following: Rho-related GTP-binding protein RhoB (196 aa, ~22 kDa) is encoded by the human RHOB gene. This protein plays a role in the modulation of protein trafficking and the inhibition of tumorigenesis.. CCL5 defined as following: A member of the IL-8 superfamily of cytokines and released from platelets and activated T-cells, RANTES is a selective chemoattractant for eosinophils, monocytes, and T-lymphocytes. RANTES is one of the ligands for chemokine receptor CCR5. RANTES expression in peripheral lymphocytes increases exponentially following mitogenic or antigenic stimulation. RANTES is one of the major HIV-suppressive factors produced by CD8-positive T-cells.. RhoA defined as following: Transforming protein RhoA (193 aa, ~22 kDa) is encoded by the human RHOA gene. This protein is involved in the regulation of signal transduction pathways that control assembly of focal adhesions and actin stress fibers.. P-Rex1 defined as following: Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein (1659 aa, ~186 kDa) is encoded by the human PREX1 gene. This protein is involved in the propagation of intracellular signaling through guanine nucleotide exchange activity.. H-Ras defined as following: Human HRAS wild-type allele is located in the vicinity of 11p15.5 and is approximately 3 kb in length. This allele, which encodes GTPase HRas protein, is involved in cellular mitogenesis. Mutations of HRAS are implicated in Costello syndrome, bladder cancer and oral squamous cell carcinoma.. actin cytoskeleton defined as following: The part of the cytoskeleton (the internal framework of a cell) composed of actin and associated proteins. Includes actin cytoskeleton-associated complexes. [GOC:jl, ISBN:0395825172, ISBN:0815316194]. GEF defined as following: Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.. GTPases defined as following: Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.. ELMO1 defined as following: This gene plays a role in phagocytosis and signal transduction.. Rac3 defined as following: Ras-related C3 botulinum toxin substrate 3 (192 aa, ~21 kDa) is encoded by the human RAC3 gene. This protein is involved in the formation of lamellipodia and membrane ruffles.. RhoGDI2 defined as following: A rho GDP-dissociation inhibitor subtype that is highly expressed in hematopoietic cells and in LYMPHOCYTES. The expression of this subtype is associated with the regulation of CELL PROLIFERATION; TUMORIGENESIS; and APOPTOSIS.. PAK1 defined as following: Human PKN1 wild-type allele is located in the vicinity of 19p13.12 and is approximately 39 kb in length. This allele, which encodes serine/threonine-protein kinase N1 protein, plays a role in the phosphorylation of intermediate filaments and histone H3.. endothelial cells defined as following: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. Rac defined as following: An index reflecting the extent of drug accumulation in the body. It is usually expressed as the ratio of the area under a plasma concentration-time curve (AUC) during a dosage interval at steady state compared to the AUC of a dosage interval after the first dose. It is affected by rate of dose administration, bioavailability, and clearance.. cancer cells defined as following: Cells of, or derived from, a malignant tumor.. Rac proteins defined as following: A sub-family of RHO GTP-BINDING PROTEINS that is involved in regulating the organization of cytoskeletal filaments. This enzyme was formerly listed as EC 3.6.1.47.. Dock180 defined as following: Dedicator of cytokinesis protein 1 (1865 aa, ~215 kDa) is encoded by the human DOCK1 gene. This protein is involved in phagocytosis, apoptosis and signaling.. MDA-MB-435 defined as following: A cell line established at M.D. Anderson Cancer Center in 1976 from the pleural effusion of a 31 year old female patient with history of breast cancer. Gene expression analysis of the MDA-MB-435 cell line has revealed that the pattern of gene expression resembles that of melanoma cell lines. Further investigation has revealed that breast-specific genes were not expressed and melanocytic-specific genes were expressed in this cell line.. cytoplasm defined as following: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990). CCR1 defined as following: C-C chemokine receptor type 1 (355 aa, ~41 kDa) is encoded by the human CCR1 gene. This protein plays a role in chemokine-mediated signaling.. MMP-2 defined as following: A secreted endopeptidase homologous with INTERSTITIAL COLLAGENASE, but which possesses an additional fibronectin-like domain.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. tumor cell defined as following: Cells of, or derived from, a tumor.. RhoC defined as following: This gene plays a role in signal transduction. It is involved in several cellular functions including cytoskeletal remodeling and cell differentiation.. breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. Cdc42 defined as following: Cell division control protein 42 homolog (191 aa, ~21 kDa) is encoded by the human CDC42 gene. This protein is involved in cell cycle regulation, actin polymerization and GTP hydrolysis.. N-Ras defined as following: This gene plays a role in signal transduction and cell cycle regulation.. ERK defined as following: A superfamily of PROTEIN SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).. Sema3A defined as following: The prototypical and most well-studied member of the semaphorin family. Semaphorin-3A is an axon-repulsive guidance cue for migrating neurons in the developing nervous system. It has so far been found only in vertebrates, and binds to NEUROPILIN-1/plexin complex receptors on growth cones. Like other class 3 semaphorins, it is a secreted protein.. cytoskeletal protein defined as following: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.. Rac1 defined as following: This gene is involved in both cell motility and signal transduction.. molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. VASP defined as following: Vasodilator-stimulated phosphoprotein (380 aa, ~40 kDa) is encoded by the human VASP gene. This protein is involved in both cell motility and cell adhesion.. pancreatic cancer defined as following: A primary or metastatic malignant tumor involving the pancreas. Representative examples include carcinoma and lymphoma.. AP-1 defined as following: A multiprotein complex composed of the products of c-jun and c-fos proto-oncogenes. These proteins must dimerize in order to bind to the AP-1 recognition site, also known as the TPA-responsive element (TRE). AP-1 controls both basal and inducible transcription of several genes.. ROS defined as following: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.. integrin defined as following: A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors (RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.. molecular defined as following: Relating to or produced by or consisting of molecules.. RNA defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). myosin defined as following: A diverse superfamily of proteins that function as translocating proteins. They share the common characteristics of being able to bind ACTINS and hydrolyze MgATP. Myosins generally consist of heavy chains which are involved in locomotion, and light chains which are involved in regulation. Within the structure of myosin heavy chain are three domains: the head, the neck and the tail. The head region of the heavy chain contains the actin binding domain and MgATPase domain which provides energy for locomotion. The neck region is involved in binding the light-chains. The tail region provides the anchoring point that maintains the position of the heavy chain. The superfamily of myosins is organized into structural classes based upon the type and arrangement of the subunits they contain.. human defined as following: Members of the species Homo sapiens.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. gastric cancer defined as following: A primary or metastatic malignant neoplasm involving the stomach.. actin defined as following: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle..", "label": "yes"} {"id": "converted_2902", "sentence1": "Is lithium effective for treatment of amyotrophic lateral sclerosis?", "sentence2": "In terms of disease-modifying treatment options, several drugs such as dexpramipexole, pioglitazone, lithium, and many others have been tested in large multicenter trials, albeit with disappointing results., Despite several positive case reports and short studies, further controlled researches have failed to substantiate any positive effects of lithium exposure in amyotrophic lateral sclerosis. , The effect of lithium was different for UNC13A carriers (p = 0.027), but not for C9orf72 carriers (p = 0.22). The 12-month survival probability for UNC13A carriers treated with lithium carbonate improved from 40.1% (95% CI 23.2-69.1) to 69.7% (95% CI 50.4-96.3)., Studies in ALS showed consistently negative results and presented evidence against the use of lithium for the treatment of this disease., BACKGROUND\nLithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival., In a pilot clinical study that we recently published we found that lithium administration slows the progression of Amyotrophic Lateral Sclerosis (ALS) in human patients., BACKGROUND Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival., BACKGROUND A neuroprotective effect of lithium in amyotrophic lateral sclerosis (ALS) has been recently reported., Lithium delays progression of amyotrophic lateral sclerosis.ALS is a devastating neurodegenerative disorder with no effective treatment. , Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial.When you're short of breath, it's hard or uncomfortable for you to take in the oxygen your body needs. You may feel as if you're not getting enough air. Sometimes you can have mild breathing problems because of a stuffy nose or intense exercise. But shortness of breath can also be a sign of a serious disease.
Many conditions can make you feel short of breath:
If you often have trouble breathing, it is important to find out the cause.
. AF defined as following: Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.. pulmonary hypertension defined as following: Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.. myocardial ischemia defined as following: Thickening and loss of elasticity of the CORONARY ARTERIES, leading to progressive arterial insufficiency (CORONARY DISEASE).. heart disease defined as following: Pathological conditions involving the HEART including its structural and functional abnormalities.. cardiovascular defined as following: The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body.. sudden cardiac death defined as following: Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005). stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810). sleep apnea defined as following: Disorders characterized by multiple cessations of respirations during sleep that induce partial arousals and interfere with the maintenance of sleep. Sleep apnea syndromes are divided into central (see SLEEP APNEA, CENTRAL), obstructive (see SLEEP APNEA, OBSTRUCTIVE), and mixed central-obstructive types.. polycythemia defined as following: An increase in the total red cell mass of the blood. (Dorland, 27th ed). cardiac arrhythmias defined as following: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction..", "label": "yes"} {"id": "converted_3706", "sentence1": "Do genes with monoallelic expression contribute proportionally to genetic diversity in humans?", "sentence2": "Genes with monoallelic expression contribute disproportionately to genetic diversity in humans., An unexpectedly large number of human autosomal genes are subject to monoallelic expression (MAE). Our analysis of 4,227 such genes uncovers surprisingly high genetic variation across human populations. This increased diversity is unlikely to reflect relaxed purifying selection. Remarkably, MAE genes exhibit an elevated recombination rate and an increased density of hypermutable sequence contexts. However, these factors do not fully account for the increased diversity. We find that the elevated nucleotide diversity of MAE genes is also associated with greater allelic age: variants in these genes tend to be older and are enriched in polymorphisms shared by Neanderthals and chimpanzees. Both synonymous and nonsynonymous alleles of MAE genes have elevated average population frequencies. We also observed strong enrichment of the MAE signature among genes reported to evolve under balancing selection. We propose that an important biological function of widespread MAE might be the generation of cell-to-cell heterogeneity; the increased genetic variation contributes to this heterogeneity., Genes with monoallelic expression contribute disproportionately to genetic diversity in humans[SEP]Relations: myoclonic-astastic epilepsy has relations: disease_protein with RAPGEF2, disease_protein with RAPGEF2, disease_protein with SLC6A1, disease_protein with SLC6A1, disease_phenotype_positive with Developmental regression, disease_phenotype_positive with Developmental regression, disease_protein with AP2M1, disease_protein with AP2M1, disease_phenotype_positive with Global developmental delay, disease_phenotype_positive with Global developmental delay. Definitions: polymorphisms defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.. humans defined as following: Members of the species Homo sapiens.. Neanderthals defined as following: Common name for an extinct species of the Homo genus. Fossils have been found in Europe and Asia. Genetic evidence suggests that limited interbreeding with modern HUMANS (Homo sapiens) took place.. MAE defined as following: A generalized myoclonic-atonic seizure is a type of generalized motor seizure characterized by a myoclonic jerk followed by an atonic motor component. [HPO:jalbers, PMID:28276060, PMID:28276064]. Genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "no"} {"id": "converted_4647", "sentence1": "Is telomestatin, a novel statin drug used to treat high cholesterol?", "sentence2": "Telomestatin is a natural product isolated from Streptomyces anulatus 3533-SV4 and has been shown to be a very potent telomerase inhibitor., Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular g-quadruplex., Activity of a novel G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095), , G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095),, We found that treatment with telomestatin reproducibly inhibited telomerase activity in the BCR-ABL-positive leukemic cell lines, A novel telomerase inhibitor, telomestatin, isolated from Streptomyces anulatus is the most potent telomerase inhibitor so far., Telomerase inhibitor, telomestatin, a specific mechanism to interact with telomere structure, Telomestatin specifically inhibited telomerase without affecting reverse transcriptases and polymerases., In addition, telomestatin induced telomere shortening, but its ratio was extremely faster than that observed in physiological telomere shortening., A novel telomerase inhibitor, telomestatin, isolated from Streptomyces anulatus is the most potent telomerase inhibitor so far. , ructure has been yet resolved for the complex with telomestatin, one of the most promising G-quadruplex-targeting anticancer drug candidates. Here, Telomestatin, a strong telomerase inhibitor with G-quadruplex stabilizing activity, is a potential therapeutic agent for treating cancers., Thus, telomestatin provide the novel therapeutic molecular target for cancer chemotherapy., Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin: in vitro and in vivo studies in acute leukemia., Activity of a novel G-quadruplex-interactive telomerase inhibitor, telomestatin (SOT-095), against human leukemia cells: involvement of ATM-dependent DNA damage response pathways.[SEP]Relations: telomerase inhibitor activity has relations: molfunc_protein with POT1, molfunc_protein with POT1, molfunc_protein with TEN1, molfunc_protein with TEN1, molfunc_protein with PINX1, molfunc_protein with PINX1, molfunc_protein with PIF1, molfunc_protein with PIF1. Telomere Extension By Telomerase has relations: pathway_protein with TERT, pathway_protein with TERT. Definitions: telomerase defined as following: An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.. acute leukemia defined as following: A clonal (malignant) hematopoietic disorder with an acute onset, affecting the bone marrow and the peripheral blood. The malignant cells show minimal differentiation and are called blasts, either myeloid blasts (myeloblasts) or lymphoid blasts (lymphoblasts).. human defined as following: Members of the species Homo sapiens.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. telomere defined as following: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.. Telomerase inhibitor defined as following: Any substance that inhibits telomerase, a ribonucleoprotein enzyme complex that adds telomeric sequences to the 3-ends of eukaryotic chromosomes. Telomerase is quiescent in most normal cells but active in most tumors..", "label": "no"} {"id": "converted_1430", "sentence1": "Is the UGT1A1*28 polymorphism associated with irinotecan response in Caucasians?", "sentence2": "These variants are associated with greater risk of serious toxicity., Homozygous carriers of UGT1A1*28 as well as those with additional UGT1A variants can suffer from severe irinotecan toxicity[SEP]Relations: Irinotecan has relations: drug_protein with UGT1A1, drug_protein with UGT1A1, drug_protein with UGT1A9, drug_protein with UGT1A9, drug_protein with CYP3A7, drug_protein with CYP3A7, drug_protein with CYP3A4, drug_protein with CYP3A4, drug_protein with TOP1MT, drug_protein with TOP1MT. Definitions: variants defined as following: An alteration or difference from a norm or standard.. UGT1A defined as following: Human UGT1A1 wild-type allele is located in the vicinity of 2q37 and is approximately 13 kb in length. This allele, which encodes UDP-glucuronosyltransferase 1-1 protein, plays a role in the transformation of small lipophilic molecules into water-soluble metabolites. Certain allelic variants of the UGT1A1 gene cause Crigler-Najjar syndrome type I, type II, Gilbert syndrome or transient familial neonatal hyperbilirubinemia.. irinotecan defined as following: A semisynthetic derivative of camptothecin, a cytotoxic, quinoline-based alkaloid extracted from the Asian tree Camptotheca acuminata. Irinotecan, a prodrug, is converted to a biologically active metabolite 7-ethyl-10-hydroxy-camptothecin (SN-38) by a carboxylesterase-converting enzyme. One thousand-fold more potent than its parent compound irinotecan, SN-38 inhibits topoisomerase I activity by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks that inhibit DNA replication and trigger apoptotic cell death. Because ongoing DNA synthesis is necessary for irinotecan to exert its cytotoxic effects, it is classified as an S-phase-specific agent.. UGT1A1*28 defined as following: Human UGT1A1*28 allele is located in the vicinity of 2q37 and is approximately 13 kb in length. This allele, which encodes UDP-glucuronosyltransferase 1-1 protein, plays a role in the transformation of small lipophilic molecules into water-soluble metabolites. UGT1A1*28 allele has a polymorphism in the promoter region that is associated with decreased transferase activity and decreases in both tolerance and effectiveness of cancer therapeutics and antiviral drugs.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. polymorphism defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level..", "label": "yes"} {"id": "converted_985", "sentence1": "Is JTV519 (K201) a potential drug for the prevention of arrhythmias?", "sentence2": "We compared the suppressive effect of K201 (JTV519), a multiple-channel blocker and cardiac ryanodine receptor-calcium release channel (RyR2) stabilizer, with that of diltiazem, a Ca(2+ )channel blocker, in 2 studies of isoproterenol-induced (n = 30) and ischemic-reperfusion-induced VAs (n = 38) in rats. , After administration of isoproterenol under Ca(2+) loading, fatal VA frequently occurred in the vehicle (9 of 10 animals, 90%) and diltiazem (8 of 10, 80%) groups, and K201 significantly suppressed the incidences of arrhythmia and mortality (2 of 10, 20%). In the reperfusion study, the incidence and the time until occurrence of reperfusion-induced VA and mortality were significantly suppressed in the K201 (2 of 15 animals, 13%) and diltiazem (1 of 9 animals, 11%) groups compared to the vehicle group (8 of 14 animals, 57%). , K201 markedly suppressed both the isoproterenol-induced and the reperfusion-induced VAs, whereas diltiazem did not suppress the isoproterenol-induced VA., JTV519 (K201) is a newly developed 1,4-benzothiazepine drug with antiarrhythmic and cardioprotective properties. It appears to be very effective in not only preventing but also in reversing the characteristic myocardial changes and preventing lethal arrhythmias., The novel antiarrhythmic drug K201 (4-[3-{1-(4-benzyl)piperidinyl}propionyl]-7-methoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine monohydrochloride) is currently in development for treatment of atrial fibrillation. K201 not only controls intracellular calcium release by the ryanodine receptors, but also possesses a ventricular action that might predispose to torsade de pointes arrhythmias. , The RyR is currently used as a therapeutic target in malignant hyperthermia where dantrolene is effective and to relieve ventricular arrhythmia, with the use of JTV519 and flecainide., Finally, KN-3 and JTV519, two compounds that stabilize RyR2 in the closed state, prevent the induction of triggered activity and suppress the inducibility of sustained AF. , JTV-519 greatly reduced the frequency of ouabain-induced arrhythmogenic events., Stabilization of RyR2 by JTV-519 effectively reduces these triggered arrhythmias., These findings may reveal the anti-arrhythmic potential of K201., The preferential ryanodine receptor stabilizer (K201) possesses antiarrhythmic effects through calcium regulation. , The drug K201 (JTV-519) increases inotropy and suppresses arrhythmias in failing hearts, but the effects of K201 on normal hearts is unknown. , K201 fails to prevent DADs in RyR2(R4496C+/-) myocytes and ventricular arrhythmias in RyR2(R4496C+/-) mice, In vivo administration of K201 failed to prevent induction of polymorphic ventricular tachycardia (VT) in RyR2(R4496C+/-) mice., The 1,4-benzothiazepine JTV519, which increases the binding affinity of calstabin-2 for RyR2, inhibited the diastolic SR Ca2+ leak, monophasic action potential alternans and triggered arrhythmias., In arrhythmias, the calstabin2 stabiliser JTV519 did not prevent arrhythmias in calstabin2-/- mice, but reduced the arrhythmias in calstabin2+/- mice, illustrating the antiarrhythmic potential of stabilising calstablin2. , In three models of arrhythmias, the calstabin2 stabiliser JTV519 did not prevent arrhythmias in calstabin2(-/-) mice, but reduced the arrhythmias in calstabin2(+/-) mice, illustrating the antiarrhythmic potential of stabilising calstabin2. , A derivative of 1,4-benzothiazepine (JTV519) increased the affinity of calstabin2 for RyR2, which stabilized the closed state of RyR2 and prevented the Ca2+ leak that triggers arrhythmias. , JTV-519 had significant protective effects on atrial fibrillation in the canine sterile pericarditis model, mainly by increasing effective refractory period, suggesting that it may have potential as a novel antiarrhythmic agent for atrial fibrillation., JTV-519 significantly decreased the mean number of sustained atrial fibrillation episodes (from 4.2 +/- 2.9 to 0 +/- 0, P < 0.01). , We conclude that JTV-519 can exert antiarrhythmic effects against AF by inhibiting repolarizing K(+) currents. The drug may be useful for the treatment of AF in patients with ischaemic heart disease.[SEP]Relations: Arrhythmia has relations: drug_effect with Oseltamivir, drug_effect with Oseltamivir, drug_effect with Venlafaxine, drug_effect with Venlafaxine, drug_effect with Levonorgestrel, drug_effect with Levonorgestrel, drug_effect with Ranitidine, drug_effect with Ranitidine. Dantrolene has relations: drug_drug with JNJ-26489112, drug_drug with JNJ-26489112. Definitions: flecainide defined as following: A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial ARRHYTHMIAS and TACHYCARDIAS.. dantrolene defined as following: Skeletal muscle relaxant that acts by interfering with excitation-contraction coupling in the muscle fiber. It is used in spasticity and other neuromuscular abnormalities. Although the mechanism of action is probably not central, dantrolene is usually grouped with the central muscle relaxants.. arrhythmia defined as following: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.. RyR defined as following: A voltage-gated calcium-release channel complex of the sarcoplasmic or endoplasmic reticulum. It plays an important role in the excitation-contraction (E-C) coupling of muscle cells. RyR comprises a family of ryanodine receptors, widely expressed throughout the animal kingdom. [GOC:ame, PMID:22822064]. ventricular arrhythmias defined as following: A disorder characterized by an electrocardiographic finding of an atypical cardiac rhythm resulting from a pathologic process in the cardiac ventricles.. malignant hyperthermia defined as following: Rapid and excessive rise of temperature accompanied by muscular rigidity following general anesthesia.. drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. VT defined as following: An abnormally rapid ventricular rhythm usually in excess of 150 beats per minute. It is generated within the ventricle below the BUNDLE OF HIS, either as autonomic impulse formation or reentrant impulse conduction. Depending on the etiology, onset of ventricular tachycardia can be paroxysmal (sudden) or nonparoxysmal, its wide QRS complexes can be uniform or polymorphic, and the ventricular beating may be independent of the atrial beating (AV dissociation).. isoproterenol defined as following: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.. myocytes defined as following: Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal (MUSCLE FIBERS, SKELETAL), cardiac (MYOCYTES, CARDIAC), and smooth (MYOCYTES, SMOOTH MUSCLE). They are derived from embryonic (precursor) muscle cells called MYOBLASTS.. polymorphic defined as following: The quality or state of being able to assume different forms.. pericarditis defined as following: Inflammation of the PERICARDIUM from various origins, such as infection, neoplasm, autoimmune process, injuries, or drug-induced. Pericarditis usually leads to PERICARDIAL EFFUSION, or CONSTRICTIVE PERICARDITIS.. ventricular arrhythmia defined as following: An electrocardiographic finding of an atypical cardiac rhythm resulting from a pathologic process in the cardiac ventricles.. diltiazem defined as following: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.. ventricular tachycardia defined as following: An electrocardiographic finding of three or more consecutive complexes of ventricular organ with a rate greater than a certain threshold (100 or 120 beats per minute are commonly used). The QRS complexes are wide and have an abnormal morphology. (CDISC). rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. atrial fibrillation defined as following: An electrocardiographic finding of a supraventricular arrhythmia characterized by the replacement of consistent P waves by rapid oscillations or fibrillatory waves that vary in size, shape and timing and are accompanied by an irregularly irregular ventricular response. (CDISC). canine defined as following: The formula to calculate body surface area in dogs. It is mathematically defined as: BSA (m^2) = (10.0 x Weight(g)^2/3)/1000. ischaemic heart disease defined as following: Thickening and loss of elasticity of the CORONARY ARTERIES, leading to progressive arterial insufficiency (CORONARY DISEASE).. arrhythmias defined as following: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction..", "label": "yes"} {"id": "converted_1475", "sentence1": "Is aganglionic megacolon a feature of Down syndrome?", "sentence2": "Down syndrome (DS) is recognized by characteristic facial features, intellectual disability, and an increased risk for cardiac malformations and duodenal atresia. Recently, Hirschsprung disease (HSCR), or congenital aganglionic megacolon, has been seen more often among patients with DS, Of the 17 patients with HD who were studied, 10 were isolated (58.8%) and seven (41.1%) were associated to other structural abnormalities and psychomotor retardation. Three of the cases in this latter group were due to chromosome pathology (trisomy 21, Down syndrome), The authors report the case of a female infant with Down syndrome, aganglionic megacolon, severe diarrhea, and jejunal biopsy with ultrastructural changes consistent with microvillous atrophy. The patient condition improved after a colostomy performed in the setting of the treatment of Hirschprung disease, Hirschsprung disease, or congenital aganglionic megacolon, is commonly assumed to be a sex-modified multifactorial trait. To test this hypothesis, complex segregation analysis was performed on data on 487 probands and their families. Demographic information on probands and the recurrence risk to relatives of probands are presented. An increased sex ratio (3.9 male:female) and an elevated risk to sibs (4%), as compared with the population incidence (0.02%), are observed, with the sex ratio decreasing and the recurrence risk to sibs increasing as the aganglionosis becomes more extensive. Down syndrome was found at an increased frequency among affected individuals but not among their unaffected sibs, and the increase was not associated with maternal age, Intestinal microvillous atrophy in a patient with Down syndrome and aganglionic megacolon., The authors report the case of a female infant with Down syndrome, aganglionic megacolon, severe diarrhea, and jejunal biopsy with ultrastructural changes consistent with microvillous atrophy., The authors report the case of a female infant with Down syndrome, aganglionic megacolon, severe diarrhea, and jejunal biopsy with ultrastructural changes consistent with microvillous atrophy., The authors report the case of a female infant with Down syndrome, aganglionic megacolon, severe diarrhea, and jejunal biopsy with ultrastructural changes consistent with microvillous atrophy[SEP]Relations: Down syndrome has relations: disease_phenotype_positive with Aganglionic megacolon, disease_phenotype_positive with Aganglionic megacolon, disease_phenotype_positive with Hypoplastic iliac wing, disease_phenotype_positive with Hypoplastic iliac wing, disease_protein with STAG2, disease_protein with STAG2. Hirschsprung disease has relations: disease_phenotype_positive with Aganglionic megacolon, disease_phenotype_positive with Aganglionic megacolon. hirschsprung disease, susceptibility to has relations: disease_phenotype_positive with Aganglionic megacolon, disease_phenotype_positive with Aganglionic megacolon. Definitions: HD defined as following: A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen.. diarrhea defined as following: An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.. aganglionosis defined as following: Congenital MEGACOLON resulting from the absence of ganglion cells (aganglionosis) in a distal segment of the LARGE INTESTINE. The aganglionic segment is permanently contracted thus causing dilatation proximal to it. In most cases, the aganglionic segment is within the RECTUM and SIGMOID COLON.. Down syndrome defined as following: A chromosome disorder associated either with an extra CHROMOSOME 21 or an effective TRISOMY for chromosome 21. Clinical manifestations include HYPOTONIA, short stature, BRACHYCEPHALY, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, single transverse palmar crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213). duodenal atresia defined as following: A congenital malformation characterized by the absence of a normal opening in a part of the duodenum.. jejunal biopsy defined as following: Removal of tissue from the jujunum for microscopic examination, using an endoscope.. intellectual disability defined as following: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28).", "label": "yes"} {"id": "converted_1570", "sentence1": "Does neuroglobin has neuroprotective properties in the setting of traumatic brain injury?", "sentence2": "Neuroglobin has shown rich neuroprotective effects against cerebral hypoxia, and therefore has the potential to impact outcomes after traumatic brain injury (TBI). , Neuroglobin (Ngb) is proposed to be a neuron-specific, hypoxia-responsive, neuroprotective protein. , CONCLUSION: The increased expression of neuroglobin in traumatic brain injury informed us that neuroglobin had anti-apoptosis action in post-injury neuron. It could protect the neuron from traumatic stress and secondary ischemia and hypoxia insults during ultra-early and acute stages., Neuroglobin-overexpression reduces traumatic brain lesion size in mice., BACKGROUND: Accumulating evidence has demonstrated that over-expression of Neuroglobin (Ngb) is neuroprotective against hypoxic/ischemic brain injuries. , CONCLUSION: Ngb over-expression reduced traumatic lesion volume, which might partially be achieved by decreasing oxidative stress., Neuroglobin upregulation offers neuroprotection in traumatic brain injury., OBJECTIVES: The aim of this study was to investigate rat neuroglobin (rNGB) expression level after traumatic brain injury (TBI) and further study its neuroprotective effects in TBI when it was overexpressed in adenoviral vector., CONCLUSIONS: NGB was upregulated in TBI and overexpressed rNGB had a significant neuroprotection in TBI. , This study suggested that rNGB overexpression may be a new strategy for treating of TBI., Neuroglobin has shown rich neuroprotective effects against cerebral hypoxia, and therefore has the potential to impact outcomes after traumatic brain injury (TBI)., The aim of this study was to investigate rat neuroglobin (rNGB) expression level after traumatic brain injury (TBI) and further study its neuroprotective effects in TBI when it was overexpressed in adenoviral vector., Accumulating evidence has demonstrated that over-expression of Neuroglobin (Ngb) is neuroprotective against hypoxic/ischemic brain injuries., Various studies seem to indicate that neuroglobin is a neuroprotective agent when overexpressed, acting as a potent inhibitor of oxidative and nitrosative stress. [SEP]Relations: brain injury has relations: contraindication with Phenobarbital, contraindication with Phenobarbital, contraindication with Isopropamide, contraindication with Isopropamide, contraindication with Homatropine, contraindication with Homatropine, contraindication with Difenoxin, contraindication with Difenoxin, contraindication with Cyclopentolate, contraindication with Cyclopentolate. Definitions: neuroglobin defined as following: A vertebrate globin that is expressed predominantly in the brain where it is involved in oxygen transport. It protects neurons from APOPTOSIS during OXIDATIVE STRESS.. neuron defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. traumatic brain injury defined as following: A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.. adenoviral vector defined as following: One of a number of genetically-engineered adenoviruses designed to insert a gene of interest into a eukaryotic cell where the gene of interest is subsequently expressed. Unlike most other vectors, adenovirus vectors have the ability to infect post-mitotic cells. Thus, these agents are especially useful for gene transfer into neuronal cells. (NCI04). hypoxia defined as following: A disorder characterized by a decrease in the level of oxygen in the body.. cerebral hypoxia defined as following: A reduction in brain oxygen supply due to ANOXEMIA (a reduced amount of oxygen being carried in the blood by HEMOGLOBIN), or to a restriction of the blood supply to the brain, or both. Severe hypoxia is referred to as anoxia and is a relatively common cause of injury to the central nervous system. Prolonged brain anoxia may lead to BRAIN DEATH or a PERSISTENT VEGETATIVE STATE. Histologically, this condition is characterized by neuronal loss which is most prominent in the HIPPOCAMPUS; GLOBUS PALLIDUS; CEREBELLUM; and inferior olives..", "label": "yes"} {"id": "converted_1241", "sentence1": "Is poly (ADP- ribosylation) involved in transcriptional control?", "sentence2": "Histone phosphorylation, ubiquitylation, SUMOylation and poly-ADP-ribosylation, as well as ATP-dependent nucleosome remodeling complexes, play equally pivotal roles in the maintenance of transcriptional fidelity, oly(ADP-ribose) polymerase-1 (PARP-1; EC 2.4.2.30) is an abundant nuclear protein that is involved in DNA repair, cell cycle control, programmed cell death and transcriptional regulation., Many lines of evidence suggest that poly(ADP-ribose) polymerase-1 (Parp-1) is involved in transcriptional regulation of various genes as a coactivator or a corepressor by modulating chromatin structure, These results suggest that Parp-1 is required to maintain transcriptional regulation of a wide variety of genes on a genome-wide scale, PARP-1 was identified as a part of the mH2A1.1 nucleosome complex and was found to be associated with the Hsp70.1 promoter, Upon heat shock, the Hsp70.1 promoter-bound PARP-1 is released to activate transcription through ADP-ribosylation of other Hsp70.1 promoter-bound proteins, Cycloheximide-induced cells were treated with two chemical inhibitors of poly(ADP-ribose) polymerase. 3-Aminobenzamide inhibited 75% of PAP gene induction and 4-hydroxyquinazolone, the highly specific inhibitor of the enzyme, blocked almost completely PAP expression, suggesting that ADP-ribosylation was indeed required for the upregulation of PAP gene expression by cycloheximide, inhibitors of poly(ADP-ribose) polymerase suppressed UV-induced HIV-1 gene expression but not tat-mediated expression, oly(ADP-ribose) polymerase inhibitors suppress UV-induced human immunodeficiency virus type 1 gene expression[SEP]Relations: TIPARP has relations: bioprocess_protein with protein mono-ADP-ribosylation, bioprocess_protein with protein mono-ADP-ribosylation, bioprocess_protein with protein ADP-ribosylation, bioprocess_protein with protein ADP-ribosylation, bioprocess_protein with protein auto-ADP-ribosylation, bioprocess_protein with protein auto-ADP-ribosylation, molfunc_protein with protein ADP-ribosylase activity, molfunc_protein with protein ADP-ribosylase activity, molfunc_protein with NAD+ ADP-ribosyltransferase activity, molfunc_protein with NAD+ ADP-ribosyltransferase activity. Definitions: Parp-1 defined as following: This gene is involved in ADP-ribosylation of proteins.. cycloheximide defined as following: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.. PAP defined as following: Blood pressure in the pulmonary artery.. corepressor defined as following: A subclass of repressor proteins that do not directly bind DNA. Instead, co-repressors generally act via their interaction with DNA-BINDING PROTEINS such as a TRANSCRIPTIONAL SILENCING FACTORS or NUCLEAR RECEPTORS.. coactivator defined as following: RNA-binding protein 14 (669 aa, ~69 kDa) is encoded by the human RBM14 gene. This protein plays a role in the modulation of gene expression.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. EC 2.4.2.30 defined as following: Poly [ADP-ribose] polymerase 2 (583 aa, ~66 kDa) is encoded by the human PARP2 gene. This protein is involved in the initiation of DNA repair..", "label": "yes"} {"id": "converted_963", "sentence1": "Is STAT3 involved in EIF2AK2-dependent suppression of autophagy?", "sentence2": "STAT3 may act as a competitive inhibitor of EIF2AK2. Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. Conversely, the overexpression of wild-type STAT3 as well as of STAT3 mutants that cannot be phosphorylated by JAK2 or are excluded from the nucleus inhibits autophagy. However, STAT3 mutants that fail to interact with EIF2AK2 are unable to suppress autophagy, Both STAT3-targeting agents (i.e., Stattic, JSI-124 and WP1066) and EIF2AK2 activators (such as the double-strand RNA mimetic polyinosinic:polycytidylic acid) are capable of disrupting the inhibitory interaction between STAT3 and EIF2AK2 in cellula, A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex, These results reveal an unsuspected crosstalk between cellular metabolism (fatty acids), pro-inflammatory signaling (STAT3), innate immunity (EIF2AK2), and translational control (EIF2S1) that regulates autophagy, Cytoplasmic STAT3 represses autophagy by inhibiting PKR activity, The SH2 domain of STAT3 was found to interact with the catalytic domain of the eIF2α kinase 2 EIF2AK2, best known as protein kinase R (PKR). Pharmacological and genetic inhibition of STAT3 stimulated the activating phosphorylation of PKR and consequent eIF2α hyperphosphorylation. Moreover, PKR depletion inhibited autophagy as initiated by chemical STAT3 inhibitors or free fatty acids like palmitate, STAT3-targeting chemicals and palmitate caused the disruption of inhibitory STAT3-PKR interactions, followed by PKR-dependent eIF2α phosphorylation, which facilitates autophagy induction, Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy., A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1., A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1, Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy, However, STAT3 mutants that fail to interact with EIF2AK2 are unable to suppress autophagy, Direct interaction between STAT3 and EIF2AK2 controls fatty acid-induced autophagy, A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1. , Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. , Direct interaction between STAT3 and EIF2AK2 controls fatty acid-induced autophagy., These results unravel an unsuspected mechanism of autophagy control that involves STAT3 and PKR as interacting partners., Both STAT3-targeting agents (i.e., Stattic, JSI-124 and WP1066) and EIF2AK2 activators (such as the double-strand RNA mimetic polyinosinic:polycytidylic acid) are capable of disrupting the inhibitory interaction between STAT3 and EIF2AK2 in cellula, yet only the latter does so in cell-free systems in vitro. A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1., A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1. These results reveal an unsuspected crosstalk between cellular metabolism (fatty acids), pro-inflammatory signaling (STAT3), innate immunity (EIF2AK2), and translational control (EIF2S1) that regulates autophagy., Thus, STAT3 may act as a competitive inhibitor of EIF2AK2. Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy., Indeed, pharmacological or genetic inhibition of STAT3 stimulates EIF2AK2-dependent EIF2S1 phosphorylation and autophagy. Conversely, the overexpression of wild-type STAT3 as well as of STAT3 mutants that cannot be phosphorylated by JAK2 or are excluded from the nucleus inhibits autophagy., , Stattic, JSI-124 and WP1066) and EIF2AK2 activators (such as the double-strand RNA mimetic polyinosinic:polycytidylic acid) are capable of disrupting the inhibitory interaction between STAT3 and EIF2AK2 in cellula, yet only the latter does so in cell-free systems in vitro. A further screen designed to identify EIF2AK2-dependent autophagy inducers revealed that several fatty acids including palmitate trigger autophagy via a pathway that involves the disruption of the STAT3-EIF2AK2 complex as well as the phosphorylation of mitogen-activated protein kinase 8/c-Jun N-terminal kinase 1 (MAPK8/JNK1) and EIF2S1.[SEP]Relations: EIF2AK2 has relations: protein_protein with STAT3, protein_protein with STAT3, protein_protein with STAT2, protein_protein with STAT2, protein_protein with STAT1, protein_protein with STAT1, pathway_protein with Inhibition of PKR, pathway_protein with Inhibition of PKR, molfunc_protein with protein phosphatase regulator activity, molfunc_protein with protein phosphatase regulator activity. Definitions: WP1066 defined as following: An orally bioavailable, small molecule inhibitor of signaling transducer and activator 3 (STAT3), with potential antineoplastic and immunomodulatory activities. Upon administration, STAT3 inhibitor WP1066 blocks the intranuclear translocation of p-STAT, thereby suppressing STAT3 signaling and decreasing the levels of downstream products including c-Myc. Additionally, WP1066 may upregulate costimulatory molecules including CD80 and CD86 on human microglia, and reverse glioma cancer stem cell (gCSC)-mediated innate and adaptive immune suppression allowing for the restoration of antitumor effector immune responses. The STAT3 pathway is overly active in many cancer types and is implicated in CSC-mediated growth, recurrence and resistance to conventional chemotherapies.. catalytic domain defined as following: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.. fatty acids defined as following: Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed). STAT3 defined as following: Signal transducer and activator of transcription 3 (770 aa, ~88 kDa) is encoded by the human STAT3 gene. This protein plays a role in cytokine signaling and gene expression.. EIF2S1 defined as following: Eukaryotic translation initiation factor 2 subunit 1 (315 aa, ~36 kDa) is encoded by the human EIF2S1 gene. This protein plays a role in the initiation of protein translation.. EIF2AK2 defined as following: This gene plays a role in the negative regulation of protein synthesis.. nucleus defined as following: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). SH2 domain defined as following: A region of protein sequence similarity among members of the SRC family of cytoplasmic tyrosine kinases, and other proteins. The SH2 domain usually mediates binding to phosphotyrosine and neighboring residues of target proteins.. polycytidylic acid defined as following: A group of cytosine ribonucleotides in which the phosphate residues of each cytosine ribonucleotide act as bridges in forming diester linkages between the ribose moieties.. PKR defined as following: A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.. JAK2 defined as following: Tyrosine-protein kinase JAK2 (1132 aa, ~131 kDa) is encoded by the human JAK2 gene. This protein is involved in immunity, tyrosine phosphorylation and signal transduction.. mitogen-activated protein kinase defined as following: A superfamily of PROTEIN SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES)..", "label": "yes"} {"id": "converted_4032", "sentence1": "Is G3BP1 found in stress granules?", "sentence2": "RAS GTPase-activating protein-binding protein (G3BP1) is an RNA-binding protein that is essential for assembling stress granules. , Within SGs, single-molecule localization microscopy revealed distributed hotspots of immobilized G3BP1 and IMP1 that reflect the presence of relatively immobile nanometer-sized nanocores., Using super-resolution and expansion microscopy, we find that the SG component UBAP2L [11, 12] and the core protein G3BP1 [5, 11-13] occupy different domains inside SGs. [SEP]Relations: stress granule assembly has relations: bioprocess_protein with G3BP1, bioprocess_protein with G3BP1, bioprocess_protein with G3BP2, bioprocess_protein with G3BP2. G3BP1 has relations: cellcomp_protein with cytoplasmic stress granule, cellcomp_protein with cytoplasmic stress granule, bioprocess_protein with stress granule assembly, bioprocess_protein with stress granule assembly, protein_protein with G3BP2, protein_protein with G3BP2. Definitions: stress granules defined as following: A dense aggregation in the cytosol composed of proteins and RNAs that appear when the cell is under stress. [GOC:ans, PMID:17284590, PMID:17601829, PMID:17967451, PMID:20368989]. SGs defined as following: A rare, autosomal dominant inherited syndrome often caused by mutations in the SKI gene. It is characterized by premature fusion of skull bones and distinctive facial features, including a long, narrow head, hypertelorism, exophthalmos, downslanting palpebral fissures, a high, narrow palate, micrognathia, and low-set ears. The bodies of affected individuals resemble those of people with Marfan syndrome..", "label": "yes"} {"id": "converted_1766", "sentence1": "Is ocrelizumab effective for treatment of multiple sclerosis?", "sentence2": " Advances made in immunomodulation are driving the progress being made in the treatment of MS. Ocrelizumab is the first treatment with positive results in the primarily progressive forms and tocilizumab, a drug product for rheumatoid arthritis, stands out as a potential candidate for the treatment of neuromyelitis optica., Expert commentary: The recent encouraging results of the ocrelizumab trial in PP MS, the first to reach the primary disability endpoint, indicate B cells as a promising therapeutic target to prevent disease progression. , Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis., Ocrelizumab for the treatment of relapsing-remitting multiple sclerosis., Expert commentary: The topline results of two phase-III randomized clinical trials demonstrate superiority of ocrelizumab over interferon beta in RRMS patients with regards to clinical and paraclinical outcome parameters. , The efficacy of three of them, rituximab, ocrelizumab and ofatumumab in MS has been confirmed by placebo-controlled clinical trials demonstrating a significant reduction of the annualized relapsing rate (ARR), new gadolinium-enhancing (GdE) and T2 lesions. , Ongoing PMS trials are currently being conducted with the phosphodiesterase inhibitor ibudilast, S1P modulator siponimod and anti-B-cell therapy ocrelizumab. , RECENT FINDINGS: Novel and imminently emerging DMTs for the treatment of RRMS include alemtuzumab, daclizumab, ocrelizumab, pegylated interferon-β-1a, and three times weekly glatiramer acetate. , To summarize mechanisms of action, efficacy, and safety of novel and imminently emerging disease-modifying treatments (DMTs) intended to be used in relapsing-remitting multiple sclerosis (RRMS).Novel and imminently emerging DMTs for the treatment of RRMS include alemtuzumab, daclizumab, ocrelizumab, pegylated interferon-β-1a, and three times weekly glatiramer acetate, Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial., We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis. , In multiple sclerosis (MS), B cell-depleting therapy using monoclonal anti-CD20 Abs, including rituximab (RTX) and ocrelizumab, effectively reduces disease activity. , Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis.Most of the presented cell-depleting and myeloablative therapies are highly effective treatment options but are also accompanied by significant risks., The armamentarium of approved disease-modifying therapies in MS and those in development include: (1) the first approved, moderately effective, injectable interferon-β and glatiramer acetate; (2) oral drugs (fingolimod, laquinimod, teriflunomide, dimethyl fumarate); (3) monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab); and (4) immunosuppressive agents (e.g. mitoxantrone)., BACKGROUND: B lymphocytes are implicated in the pathogenesis of multiple sclerosis. We aimed to assess efficacy and safety of two dose regimens of the humanised anti-CD20 monoclonal antibody ocrelizumab in patients with relapsing-remitting multiple sclerosis.METHODS: We did a multicentre, randomised, parallel, double-blind, placebo-controlled study involving 79 centres in 20 countries. Patients aged 18-55 years with relapsing-remitting multiple sclerosis were randomly assigned (1:1:1:1) via an interactive voice response system to receive either placebo, low-dose (600 mg) or high-dose (2000 mg) ocrelizumab in two doses on days 1 and 15, or intramuscular interferon beta-1a (30 ìg) once a week., Ocrelizumab for the treatment of relapsing-remitting multiple sclerosis., The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects., Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial., Ocrelizumab also shows efficacy in the primary progressive form of multiple sclerosis.[SEP]Relations: Ocrelizumab has relations: drug_drug with Otelixizumab, drug_drug with Otelixizumab, drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Crenezumab, drug_drug with Crenezumab, drug_drug with Nemolizumab, drug_drug with Nemolizumab, drug_drug with Pexelizumab, drug_drug with Pexelizumab. Definitions: ocrelizumab defined as following: A Fc-modified, humanized monoclonal antibody directed against the B-cell CD20 cell surface antigen, with immunosuppressive activity. Ocrelizumab binds to CD20 on the surfaces of B-cells, triggering complement-dependent cell lysis (CDCL) and antibody-dependent cell-mediated cytotoxicity (ADCC) of B-cells overexpressing CD20. The CD20 antigen, a non-glycosylated cell surface phosphoprotein that acts as a calcium ion channel, is found on over 90% of B-cells, B-cell lymphomas, and other lymphoid tumor cells of B-cell origin; it plays an important role in B-cell functioning.. ofatumumab defined as following: A fully human, high-affinity IgG1 monoclonal antibody directed against the B cell CD20 cell surface antigen with potential antineoplastic activity. Ofatumumab binds specifically to CD20 on the surfaces of B cells, triggering complement-dependent cell lysis (CDCL) and antibody-dependent cell-mediated cytotoxicity (ADCC) of B cells overexpressing CD20. The CD20 antigen, found on over 90% of B cells, B cell lymphomas, and other B cells of lymphoid tumors of B cell origin, is a non-glycosylated cell surface phosphoprotein that acts as a calcium ion channel; it is exclusively expressed on B cells during most stages of B cell development.. interferon beta defined as following: A recombinant protein which is chemically identical to or similar to endogenous interferon beta with antiviral and anti-tumor activities. Endogenous interferons beta are cytokines produced by nucleated cells (predominantly natural killer cells) upon exposure to live or inactivated virus, double-stranded RNA or bacterial products. These agents bind to specific cell-surface receptors, resulting in the transcription and translation of genes with an interferon-specific response element. The proteins so produced mediate many complex effects, including antiviral (the most important being inhibition of viral protein synthesis), antiproliferative and immune modulating effects. The recombinant therapeutic forms of interferon beta are interferon beta 1-a and interferon beta 1-b. (NCI05). glatiramer acetate defined as following: A random polymer of L-ALANINE, L-GLUTAMIC ACID, L-LYSINE, and L-TYROSINE that structurally resembles MYELIN BASIC PROTEIN. It is used in the treatment of RELAPSING-REMITTING MULTIPLE SCLEROSIS.. interferon beta-1a defined as following: A recombinant form of the endogenous cytokine human interferon (IFN) beta-1a, with antiproliferative, antiviral and immunomodulating activities. Upon administration, interferon beta-1a targets and binds to specific type I IFN receptors, which eventually results in the transcription and translation of genes containing an interferon-specific response element and leads to the production of various anti-viral proteins and modulates the production of various immune-modulating proteins. This reduces the production of certain pro-inflammatory cytokines while upregulating the anti-inflammatory cytokine interleukin 10 (IL-10), upregulates the expression of major histocompatibility (MHC) I proteins which allows for increased presentation of peptides derived from viral antigens, and activates CD8+ T cells as well as other immune cells. Endogenous IFN-beta-1a is produced following viral infection and it plays a key role in innate immune response against viral pathogens.. alemtuzumab defined as following: Any monoclonal antibody directed against the cell surface glycoprotein CD52, regardless of the antibody type (e.g., rat, mouse, humanized).. daclizumab defined as following: An anti-TAC (INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT) humanized monoclonal antibody (immunoglobulin G1 disulfide with human-mouse monoclonal clone 1H4 light chain, dimer) that is used in the treatment of ACUTE RELAPSING MULTIPLE SCLEROSIS.. rheumatoid arthritis defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. rituximab defined as following: A murine-derived monoclonal antibody and ANTINEOPLASTIC AGENT that binds specifically to the CD20 ANTIGEN and is used in the treatment of LEUKEMIA; LYMPHOMA and RHEUMATOID ARTHRITIS.. relapsing-remitting multiple sclerosis defined as following: The most common clinical variant of MULTIPLE SCLEROSIS, characterized by recurrent acute exacerbations of neurologic dysfunction followed by partial or complete recovery. Common clinical manifestations include loss of visual (see OPTIC NEURITIS), motor, sensory, or bladder function. Acute episodes of demyelination may occur at any site in the central nervous system, and commonly involve the optic nerves, spinal cord, brain stem, and cerebellum. (Adams et al., Principles of Neurology, 6th ed, pp903-914). multiple sclerosis defined as following: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903). ibudilast defined as following: An orally bioavailable inhibitor of cyclic nucleotide phosphodiesterase (PDE), mainly PDE-3, -4, -10, and -11, with anti-(neuro)inflammatory, vasorelaxant, bronchodilator, analgesic, neuroprotective and potential anti-tumor activities. Ibudilast (IBD) is able to cross the blood-brain barrier (BBB). Upon administration, IBD exerts its potential anti-tumor activity against glioblastoma multiforme (GBM) cells by inhibiting PDE-4 and the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF), which results in a decrease in MIF, its receptor CD74, and AKT expression, and attenuates the immunosuppressive properties of monocytic myeloid-derived suppressor cells (MDSCs) and reduces T-regulatory cells (Tregs). This causes GBM cell apoptosis and inhibits GBM cell proliferation. In addition, IBD reduces, through its inhibitory effect on various PDEs, the production of certain pro-inflammatory cytokines, such as interleukin-6 (IL-6), IL- 1beta, leukotriene B4, and tumor necrosis factor-alpha (TNF-a). IBD also upregulates the anti-inflammatory cytokine (IL-10), and promotes the production of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-4 (NT-4). It also blocks toll-like receptor-4 (TLR-4), inhibits nitric oxide (NO) synthesis and reduces the level of reactive oxygen species (ROS). It also prevents platelet aggregation, causes cerebral vasodilation, bronchial smooth muscle relaxation, and improves cerebral blood flow. In addition, IBD attenuates the PDE-mediated activation of glial cells and abrogates PDE-mediated neuroinflammation and neurodegeneration. MIF is secreted by cancer stem cells (CSCs) and is highly expressed within GBM and plays a key role in tumor cell proliferation. Co-expression of MIF and CD74 in GBM is associated with poor patient survival.. fingolimod defined as following: An orally available derivate of myriocin and sphingosine-1-phosphate receptor 1 (S1PR1, S1P1) modulator, with potential anti-inflammatory and immunomodulating activities. Upon oral administration, fingolimod, as a structural analogue of sphingosine, selectively targets and binds to S1PR1 on lymphocytes and causes transient receptor activation followed by S1PR1 internalization and degradation. This results in the sequestration of lymphocytes in lymph nodes. By preventing egress of lymphocytes. fingolimod reduces both the amount of circulating peripheral lymphocytes and the infiltration of lymphocytes into target tissues. This prevents a lymphocyte-mediated immune response and may reduce inflammation. S1PR1, a G-protein coupled receptor, plays a key role in lymphocyte migration from lymphoid tissues. Fingolimod also shifts macrophages to an anti-inflammatory M2 phenotype, and modulates their proliferation, morphology, and cytokine release via inhibition of the transient receptor potential cation channel, subfamily M, member 7 (TRPM7).. PMS defined as following: An exceedingly rare autosomal dominant developmental anomaly reported in 1986 in nine individuals among four generations of the same family. The syndrome has clinical characteristics of four-limb postaxial polydactyly and progressive myopia. There have been no further descriptions in the literature since 1986.. low-dose defined as following: A reduced quantity of a therapeutic agent prescribed to be taken at one time or at stated intervals.. dimethyl fumarate defined as following: An orally bioavailable methyl ester of fumaric acid and activator of nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2, Nfe2l2), with potential neuroprotective, immunomodulating and radiosensitizing activities. Although the exact mechanism of action through which dimethyl fumarate exerts its neuroprotective and immunomodulatory effects have yet to be fully understood, upon oral administration, dimethyl fumarate is converted into its active metabolite monomethyl fumarate (MMF) and MMF binds to Nrf2. Subsequently, Nrf2 translocates to the nucleus and binds to the antioxidant response element (ARE). This induces the expression of a number of cytoprotective genes, including NAD(P)H quinone oxidoreductase 1 (NQO1), sulfiredoxin 1 (Srxn1), heme oxygenase-1 (HO1, HMOX1), superoxide dismutase 1 (SOD1), gamma-glutamylcysteine synthetase (gamma-GCS), thioredoxin reductase-1 (TXNRD1), glutathione S-transferase (GST), glutamate-cysteine ligase catalytic subunit (Gclc) and glutamate-cysteine ligase regulatory subunit (Gclm); this also increases the synthesis of the antioxidant glutathione (GSH). The intraneuronal synthesis of GSH may protect neuronal cells from damage due to oxidative stress. Dimethyl fumarate also appears to inhibit the nuclear factor-kappa B (NF-kB)-mediated pathway, modulates the production of certain cytokines and induces apoptosis in certain T-cell subsets. Its radiosensitizing activity is due to this agent's ability to bind to and sequester intracellular GSH, thereby depleting intracellular GSH and preventing its anti-oxidative effects. This enhances the cytotoxicity of ionizing radiation in hypoxic cancer cells. Nrf2, a leucine zipper transcription factor, plays a key role in redox homeostasis and cytoprotection against oxidative stress.. B cells defined as following: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.. mitoxantrone defined as following: An anthracenedione-derived antineoplastic agent.. RTX defined as following: A naturally occurring capsaicin analog found in the latex of the cactus Euphorbia resinifera with analgesic activity. Resiniferatoxin (RTX) binds to and activates the transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel in the plasma membrane of primary afferent sensory neurons. This increases the permeability to cations, and leads to an influx of calcium and sodium ions. This results in membrane depolarization, causing an irritant effect, followed by desensitization of the sensory neurons thereby inhibiting signal conduction in afferent pain pathways and causing analgesia. TRPV1, a member of the transient receptor potential channel (TRP) superfamily, is a heat- and chemo-sensitive calcium/sodium ion channel that is selectively expressed in a subpopulation of pain-sensing primary afferent neurons.. drug product defined as following: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.. tocilizumab defined as following: A recombinant, humanized IgG1 monoclonal antibody directed against the interleukin-6 receptor (IL-6R) with immunosuppressant activity. Tocilizumab targets and binds to both the soluble form of IL-6R (sIL-6R) and the membrane-bound form (mIL-6R), thereby blocking the binding of IL-6 to its receptor. This prevents IL-6-mediated signaling. IL-6, a pro-inflammatory cytokine that plays an important role in the regulation of the immune response, is overproduced in autoimmune disorders, certain types of cancers and possibly various other inflammatory conditions..", "label": "yes"} {"id": "converted_665", "sentence1": "Has overexpression of sirtuins been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae)?", "sentence2": "In addition, Sir2 overexpression prevents Rif1 deletion from disrupting Sir2 at IGS1 and shortening lifespan. , Roles for sirtuin proteins at telomeres are thought to promote lifespan in yeast and mammals., Overexpression of sirtuins (NAD(+)-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae), When overexpressed, the NAD-dependent protein deacetylase Sir2 extends the lifespan of both budding yeast , When overexpressed in primary mouse embryo fibroblasts (MEFs), SIRT1 antagonizes PML-induced acetylation of p53 and rescues PML-mediated premature cellular senescence. [SEP]Relations: megaloblastic anemia (disease) has relations: contraindication with Phenytoin, contraindication with Phenytoin, contraindication with Primidone, contraindication with Primidone. NAD-dependent histone deacetylase activity has relations: molfunc_protein with SIRT1, molfunc_protein with SIRT1, molfunc_protein with SIRT2, molfunc_protein with SIRT2, molfunc_protein with SIRT3, molfunc_protein with SIRT3. Definitions: sirtuins defined as following: A homologous family of regulatory enzymes that are structurally related to the protein silent mating type information regulator 2 (Sir2) found in Saccharomyces cerevisiae. Sirtuins contain a central catalytic core region which binds NAD. Several of the sirtuins utilize NAD to deacetylate proteins such as HISTONES and are categorized as GROUP III HISTONE DEACETYLASES. Several other sirtuin members utilize NAD to transfer ADP-RIBOSE to proteins and are categorized as MONO ADP-RIBOSE TRANSFERASES, while a third group of sirtuins appears to have both deacetylase and ADP ribose transferase activities.. p53 defined as following: Human TP53 wild-type allele is located in the vicinity of 17p13.1 and is approximately 19 kb in length. This allele, which encodes cellular tumor antigen p53 protein, plays a role in cell cycle regulation during the G0/G1transition. Alterations of the TP53 gene occur as both somatic and germline mutations in human malignancies in select cancer-prone families with Li-Fraumeni syndrome.. telomeres defined as following: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.. Sir2 defined as following: Catalysis of the reaction: histone N6-acetyl-L-lysine + H2O = histone L-lysine + acetate. This reaction requires the presence of NAD, and represents the removal of an acetyl group from a histone. [PMID:28450737]. mammals defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. SIRT1 defined as following: A sirtuin family member found primarily in the CELL NUCLEUS. It is an NAD-dependent deacetylase with specificity towards HISTONES and a variety of proteins involved in gene regulation.. IGS1 defined as following: An autosomal recessive disorder caused by mutations in the CUBN or AMN genes. It is characterized by vitamin B12 deficiency due to selective malabsorption of the vitamin, and usually results in megaloblastic anemia appearing in childhood (but not immediately after birth)..", "label": "yes"} {"id": "converted_2887", "sentence1": "Is the enzyme ERAP2 associated with the disease birdshot chorioretinopathy?", "sentence2": "Allele-specific Alterations in the Peptidome Underlie the Joint Association of HLA-A*29:02 and Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) with Birdshot Chorioretinopathy., BSCR is also associated with endoplasmic reticulum aminopeptidase 2 (ERAP2), an enzyme involved in processing HLA class I ligands, thus implicating the A*29:02 peptidome in this disease. , A genome-wide association study identifies a functional ERAP2 haplotype associated with birdshot chorioretinopathy.[SEP]Relations: birdshot chorioretinopathy has relations: disease_protein with HLA-A, disease_protein with HLA-A, disease_phenotype_positive with Retinal pigment epithelial atrophy, disease_phenotype_positive with Retinal pigment epithelial atrophy, disease_phenotype_positive with Epiretinal membrane, disease_phenotype_positive with Epiretinal membrane, disease_phenotype_positive with Arcuate scotoma, disease_phenotype_positive with Arcuate scotoma. ERAP2 has relations: disease_protein with ileocolitis, disease_protein with ileocolitis. Definitions: BSCR defined as following: A form of chorioretinitis characterized by multiple small, cream-colored LESIONS, symmetrically scattered mainly around the OPTIC DISK. These lesions are the most distinctive sign and often appear at the level of the RETINAL PIGMENT EPITHELIUM but, on occasion, suggest an even deeper infiltration and may ultimately lead to visual loss. An association with HLA-A29 antigen (see HLA-A ANTIGENS) has been observed in nearly all patients.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown..", "label": "yes"} {"id": "converted_4316", "sentence1": "Is fusobacterium associated with Lemierre's syndrome?", "sentence2": "Invasive infections with Fusobacterium necrophorum including Lemierre's syndrome: an 8-year Swedish nationwide retrospective study., Lemierre's syndrome is defined as an oropharyngeal infection due to Fusobacterium necrophorum,, Lemierre's syndrome is a rare but life-threatening condition characterized by an oropharyngeal infection typically secondary to Fusobacterium necrophorum resulting in septic thrombophlebitis of the internal jugular vein. , Lemierre's syndrome is a rare condition that results from oropharyngeal infection with the gram-negative, anaerobic Fusobacterium necrophorum., INTRODUCTION: Like Fusobacterium necrophorum, Fusobacterium nucleatum is capable causing Lemierre's syndrome., [Lemierre syndrome variant: Hepatic abscesses and hepatic venous thrombosis due to Fusobacterium nucleatum septicemia]., Fusobacterium necrophorum-induced sepsis: an unusual case of Lemierre's syndrome., F necrophorum is most commonly associated with Lemierre's syndrome: a septic thrombophlebitis of the internal jugular vein., Fusobacterium necrophorum Septicemia Leading to Lemierre's Syndrome in an Immunocompetent Individual: A Case Report., We present a case of a patient with Lemierre's syndrome caused by Fusobacterium necrophorum who developed a right frontal lobe brain abscess., Lemierre's syndrome secondary to Fusobacterium necrophorum infection, a rare cause of hepatic abscess., Lemierre's syndrome is an uncommon complication of pharyngitis commonly associated with an anaerobic gram negative bacterium, Fusobacterium necrophorum., The following presentation is a case of Lemierre's syndrome in a 23-year-old healthy individual who is infected by a rare species: Fusobacterium nucleatum., However, Fusobacterium species causing Lemierre's variant gastrointestinal syndrome has only been reported in case reports., Fusobacterium species is known for being a causative agent for Lemierre's syndrome, which is characterized by thrombophlebitis of the jugular vein., The Fusobacterium species is known for its association with septic thrombophlebitis of the internal jugular vein (Lemierre's syndrome). Lemierre's syndrome is as, Lemierre's syndrome due to Fusobacterium necrophorum., Fusobacterium species are well described as the causative pathogen in Lemierre's syndrome, a suppurative thrombophlebitis of the jugular vein. However, they are less r, Introduction: Lemierre's syndrome is a rare but serious complication of an oral infection mostly related to Fusobacterium necrophorum. This condition combines j, Fusobacterium necrophorum is a gram-negative anaerobic bacterium that is the causative agent of the invasive disease Lemierre's syndrome., INTRODUCTION: Lemierre's syndrome is defined as an oropharyngeal infection due to Fusobacterium necrophorum, associated with septic thrombophlebitis of the internal , Fusobacterium nucleatum is a gram-negative bacillius commonly found in oropharynx and is traditionally associated with Lemierre syndrome, which is characterized by history of recent oropharyngeal infection, internal jugular vein thrombosis, and isolation of anaerobic pathogens, mainly Fuosobacterium necrophorum. Ho, Lemierre's syndrome is an uncommon complication of pharyngitis commonly associated with an anaerobic gram negative bacterium, Fusobacterium necrophorum. , Fusobacterium species is known for being a causative agent for Lemierre's syndrome, which is characterized by thrombophlebitis of the jugular vein. , Lemierre's syndrome is a systemic complication commonly caused by oropharyngeal infection by Fusobacterium species, which manifests itself as an internal jugular vein thrombosis formation. , Lemierre's syndrome is a rare but serious condition, characterized by disseminated infection with Fusobacterium necrophorum, most often originating from the oropharynx. T, Lemierre's syndrome is a rare clinical condition that generally develops secondary to oropharyngeal infection caused by Fusobacterium necrophorum, which is an anaerobic bacteria. , Lemierre's syndrome, a systemic anaerobic infection caused by Fusobacterium necrophorum, is characterized by an acute oropharyngeal infection, septic thrombophlebitis of the internal jugular veins, sepsis, and multiple metastatic infections. It c, Lemierre's syndrome, a systemic anaerobic infection caused by Fusobacterium necrophorum, is characterized by an acute oropharyngeal infection, septic thrombophlebitis of the internal jugular vein, sepsis, and multiple metastatic infections. It c, Fusobacterium necrophorum is a rare infection most notable for causing Lemierre's syndrome., We present a patient with an atypical presentation of Fusobacterium infection, the genus responsible for Lemierre's syndrome., INTRODUCTION: Like Fusobacterium necrophorum, Fusobacterium nucleatum is capable causing Lemier, Fusobacterium necrophorum, a well‐known cause of Lemierre's syndrome, was identified., We report an unusual case of Lemierre's syndrome due to a rare species of Fusobacterium, that is, Fusobacterium nucleatum preceded by Mycoplasma pneumoniae pharyngitis and followed later by Epstein-Barr virus infectious mononucleosis., We present a case of invasive Fusobacterium infection that meets all criteria for Lemierre syndrome except lacking internal jugular thrombosis., Fusobacterium necrophorum is ananaerobic Gram-negative bacillus and is the most common organism reported to cause Lemierre's syndrome which usually occurs one to three weeks post pharyngitis or oropharyngeal surgery., Lemierre's disease: postanginal bacteremia and pulmonary involvement caused by Fusobacterium necrophorum., Increased diagnosis of Lemierre syndrome and other Fusobacterium necrophorum infections at a Children's Hospital., The Fusobacterium species is known for its association with septic thrombophlebitis of the internal jugular vein (Lemierre's syndrome)., Fusobacterium species have rarely been implicated in cases of gastrointestinal variant of Lemierre's syndrome., Fusobacterium species are well described as the causative pathogen in Lemierre's syndrome, a suppurative thrombophlebitis of the jugular vein., F. necrophorum is unique among non-spore-forming anaerobes, first for its virulence and association with Lemierre's syndrome as a monomicrobial infection and second because it seems probable that it is an exogenously acquired infection., Fusobacteria are most often associated with the classic presentation of Lemierre's syndrome consisting of a sore throat, internal jugular vein thrombophlebitis, and septic emboli to the lungs., Fusobacterium necrophorum plays a causal role in a rare and life-threatening condition, Lemierre's syndrome., Lemierre's syndrome is a rare disorder of young adults caused by the anaerobic bacterium, Fusobacterium necrophorum and occasionally by other Fusobacterium species (F. nucleatum, F. mortiferum and F. varium etc)., Lemierre's syndrome is a severe complication of Fusobacterium necrophorum oropharyngeal infection associated with metastatic foci of infection, internal jugular vein thrombosis, and septicemia., Short blood culture time-to-positivity in Fusobacterium necrophorum bacteremia is associated with Lemierre's syndrome., The causative organisms are the anaerobic fusobacteria, most commonly Fusobacterium necrophorum., In a 3-year prospective study, all cases of disseminated Fusobacterium necrophorum infections found in Denmark from 1998 to 2001 were analysed, with the aim of describing the epidemiology and clinical features of the variants of Lemierre's syndrome and disseminated non-head-and-neck-associated F. necrophorum infections.[SEP]Relations: Lemierre syndrome has relations: disease_disease with commensal bacterial infectious disease, disease_disease with commensal bacterial infectious disease, disease_disease with bacterial infectious disease with sepsis, disease_disease with bacterial infectious disease with sepsis. Fusobacterium infectious disease has relations: disease_disease with anaerobic bacteria infectious disease, disease_disease with anaerobic bacteria infectious disease, disease_disease with anaerobic bacteria infectious disease, disease_disease with anaerobic bacteria infectious disease, disease_disease with gram-negative bacterial infections, disease_disease with gram-negative bacterial infections. Definitions: variants defined as following: An alteration or difference from a norm or standard.. pharyngitis defined as following: Inflammation of the throat (PHARYNX).. Septicemia defined as following: Systemic disease associated with the presence of pathogenic microorganisms or their toxins in the blood.. Fusobacterium infection defined as following: Infections with bacteria of the genus FUSOBACTERIUM.. Lemierre's disease defined as following: A superinfection of the damaged oropharyngeal mucosa by FUSOBACTERIUM NECROPHORUM leading to the secondary septic THROMBOPHLEBITIS of the internal jugular vein.. Hepatic abscesses defined as following: Solitary or multiple collections of PUS within the liver as a result of infection by bacteria, protozoa, or other agents.. infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. Fusobacteria defined as following: A phylum of anaerobic Gram-negative bacteria that are a normal component of the gut flora.. oropharynx defined as following: The middle portion of the pharynx that lies posterior to the mouth, inferior to the SOFT PALATE, and superior to the base of the tongue and EPIGLOTTIS. It has a digestive function as food passes from the mouth into the oropharynx before entering ESOPHAGUS.. Fusobacterium nucleatum defined as following: A species of gram-negative, anaerobic, rod-shaped bacteria isolated from the gingival margin and sulcus and from infections of the upper respiratory tract and pleural cavity.. Fusobacterium necrophorum defined as following: A species of gram-negative, non-spore-forming bacteria isolated from the natural cavities of man and other animals and from necrotic lesions, abscesses, and blood.. lungs defined as following: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.. thrombophlebitis defined as following: Inflammation of a vein associated with a blood clot (THROMBUS).. organism defined as following: A living entity.. fusobacterium defined as following: A genus of gram-negative, anaerobic, rod-shaped bacteria found in cavities of humans and other animals. No endospores are formed. Some species are pathogenic and occur in various purulent or gangrenous infections.. Lemierre's syndrome defined as following: A superinfection of the damaged oropharyngeal mucosa by FUSOBACTERIUM NECROPHORUM leading to the secondary septic THROMBOPHLEBITIS of the internal jugular vein..", "label": "yes"} {"id": "converted_2308", "sentence1": "Is there an RNAi drug being developed to treat amyloidosis?", "sentence2": "Patisiran is an investigational RNA interference (RNAi) therapeutic in development for the treatment of hereditary ATTR (hATTR) amyloidosis, a progressive disease associated with significant disability, morbidity, and mortality.[SEP]Relations: primary amyloidosis has relations: disease_disease with AL amyloidosis, disease_disease with AL amyloidosis. Definitions: amyloidosis defined as following: A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. Various signs and symptoms depend on the location and size of the deposits.. RNA defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed).", "label": "yes"} {"id": "converted_2671", "sentence1": "Is a mutation of the ZIKV's membrane protein prM responsible for the microcephaly in new-born infants?", "sentence2": "Here we show that a single serine-to-asparagine substitution [Ser139→Asn139(S139N)] in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates in neonatal mice., A single mutation in the prM protein of Zika virus contributes to fetal microcephaly.[SEP]Definitions: microcephaly defined as following: Head circumference below 2 standard deviations below the mean for age and gender. [PMID:15806441, PMID:19125436, PMID:25465325, PMID:9683597]. human defined as following: Members of the species Homo sapiens.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer..", "label": "yes"} {"id": "converted_1187", "sentence1": "Is there any link between conserved noncoding elements and alternative splicing in vertebrates?", "sentence2": "Some of the most highly conserved sequences occur in genes encoding RNA binding proteins, particularly the RNA splicing-associated SR genes. Differences in sequence conservation between plants and animals are likely to reflect differences in the biology of the organisms, with plants being much more able to tolerate genomic deletions and whole-genome duplication events due, in part, to their far greater fecundity compared with vertebrates.[SEP]Relations: vertebra has relations: anatomy_anatomy with non-transverse process-bearing vertebra, anatomy_anatomy with non-transverse process-bearing vertebra. protein binding has relations: molfunc_protein with SPRYD7, molfunc_protein with SPRYD7, molfunc_protein with SPG7, molfunc_protein with SPG7, molfunc_protein with SPIC, molfunc_protein with SPIC, molfunc_protein with SP7, molfunc_protein with SP7. Definitions: vertebrates defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes.. organisms defined as following: A living entity.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. plants defined as following: Multicellular, eukaryotic life forms of kingdom Plantae. Plants acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations. It is a non-taxonomical term most often referring to LAND PLANTS. In broad sense it includes RHODOPHYTA and GLAUCOPHYTA along with VIRIDIPLANTAE.. RNA binding proteins defined as following: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA..", "label": "yes"} {"id": "converted_3132", "sentence1": "Can you computationally predict Molecular Recognition Features (MoRFs) regions in Intrinsically Disordered Proteins (IDPs)?", "sentence2": "Predicting Functions of Disordered Proteins with MoRFpred., Intrinsically disordered proteins and regions are involved in a wide range of cellular functions, and they often facilitate protein-protein interactions. Molecular recognition features (MoRFs) are segments of intrinsically disordered regions that bind to partner proteins, where binding is concomitant with a transition to a structured conformation. MoRFs facilitate translation, transport, signaling, and regulatory processes and are found across all domains of life. A popular computational tool, MoRFpred, accurately predicts MoRFs in protein sequences. MoRFpred is implemented as a user-friendly web server that is freely available at http://biomine.cs.vcu.edu/servers/MoRFpred/ . We describe this predictor, explain how to run the web server, and show how to interpret the results it generates. We also demonstrate the utility of this web server based on two case studies, focusing on the relevance of evolutionary conservation of MoRF regions., MoRFPred-plus: Computational Identification of MoRFs in Protein Sequences using Physicochemical Properties and HMM profiles., Intrinsically Disordered Proteins (IDPs) lack stable tertiary structure and they actively participate in performing various biological functions. These IDPs expose short binding regions called Molecular Recognition Features (MoRFs) that permit interaction with structured protein regions. Upon interaction they undergo a disorder-to-order transition as a result of which their functionality arises. Predicting these MoRFs in disordered protein sequences is a challenging task.METHOD: In this study, we present MoRFpred-plus, an improved predictor over our previous proposed predictor to identify MoRFs in disordered protein sequences. Two separate independent propensity scores are computed via incorporating physicochemical properties and HMM profiles, these scores are combined to predict final MoRF propensity score for a given residue. The first score reflects the characteristics of a query residue to be part of MoRF region based on the composition and similarity of assumed MoRF and flank regions. The second score reflects the characteristics of a query residue to be part of MoRF region based on the properties of flanks associated around the given residue in the query protein sequence. The propensity scores are processed and common averaging is applied to generate the final prediction score of MoRFpred-plus.RESULTS: Performance of the proposed predictor is compared with available MoRF predictors, MoRFchibi, MoRFpred, and ANCHOR. Using previously collected training and test sets used to evaluate the mentioned predictors, the proposed predictor outperforms these predictors and generates lower false positive rate. In addition, MoRFpred-plus is a downloadable predictor, which makes it useful as it can be used as input to other computational tools., OPAL: prediction of MoRF regions in intrinsically disordered protein sequences., Intrinsically disordered proteins lack stable 3-dimensional structure and play a crucial role in performing various biological functions. Key to their biological function are the molecular recognition features (MoRFs) located within long disordered regions. Computationally identifying these MoRFs from disordered protein sequences is a challenging task. In this study, we present a new MoRF predictor, OPAL, to identify MoRFs in disordered protein sequences. OPAL utilizes two independent sources of information computed using different component predictors. The scores are processed and combined using common averaging method. The first score is computed using a component MoRF predictor which utilizes composition and sequence similarity of MoRF and non-MoRF regions to detect MoRFs. The second score is calculated using half-sphere exposure (HSE), solvent accessible surface area (ASA) and backbone angle information of the disordered protein sequence, using information from the amino acid properties of flanks surrounding the MoRFs to distinguish MoRF and non-MoRF residues.Results: OPAL is evaluated using test sets that were previously used to evaluate MoRF predictors, MoRFpred, MoRFchibi and MoRFchibi-web. The results demonstrate that OPAL outperforms all the available MoRF predictors and is the most accurate predictor available for MoRF prediction. It is available at http://www.alok-ai-lab.com/tools/opal/., OPAL+: Length-Specific MoRF Prediction in Intrinsically Disordered Protein Sequences., Intrinsically disordered proteins (IDPs) contain long unstructured regions, which play an important role in their function. These intrinsically disordered regions (IDRs) participate in binding events through regions called molecular recognition features (MoRFs). Computational prediction of MoRFs helps identify the potentially functional regions in IDRs. In this study, OPAL+, a novel MoRF predictor, is presented. OPAL+ uses separate models to predict MoRFs of varying lengths along with incorporating the hidden Markov model (HMM) profiles and physicochemical properties of MoRFs and their flanking regions. Together, these features help OPAL+ achieve a marginal performance improvement of 0.4-0.7% over its predecessor for diverse MoRF test sets. This performance improvement comes at the expense of increased run time as a result of the requirement of HMM profiles. OPAL+ is available for download at https://github.com/roneshsharma/OPAL-plus/wiki/OPAL-plus-Download., Computational Identification of MoRFs in Protein Sequences Using Hierarchical Application of Bayes Rule., Key to their regulatory function is often the binding to globular protein domains via sequence elements known as molecular recognition features (MoRFs). Development of computational tools for the identification of candidate MoRF locations in amino acid sequences is an important task and an area of growing interest. Given the relative sparseness of MoRFs in protein sequences, the accuracy of the available MoRF predictors is often inadequate for practical usage, which leaves a significant need and room for improvement. In this work, we introduce MoRFCHiBi_Web, which predicts MoRF locations in protein sequences with higher accuracy compared to current MoRF predictors.METHODS: Three distinct and largely independent property scores are computed with component predictors and then combined to generate the final MoRF propensity scores. The first score reflects the likelihood of sequence windows to harbour MoRFs and is based on amino acid composition and sequence similarity information. It is generated by MoRFCHiBi using small windows of up to 40 residues in size. The second score identifies long stretches of protein disorder and is generated by ESpritz with the DisProt option. Lastly, the third score reflects residue conservation and is assembled from PSSM files generated by PSI-BLAST. These propensity scores are processed and then hierarchically combined using Bayes rule to generate the final MoRFCHiBi_Web predictions.RESULTS: MoRFCHiBi_Web was tested on three datasets. Results show that MoRFCHiBi_Web outperforms previously developed predictors by generating less than half the false positive rate for the same true positive rate at practical threshold values., Computational identification of MoRFs in protein sequences., In this study, we introduce MoRFCHiBi, a new computational approach for fast and accurate prediction of MoRFs in protein sequences. MoRFCHiBi combines the outcomes of two support vector machine (SVM) models that take advantage of two different kernels with high noise tolerance. The first, SVMS, is designed to extract maximal information from the general contrast in amino acid compositions between MoRFs, their surrounding regions (Flanks), and the remainders of the sequences. The second, SVMT, is used to identify similarities between regions in a query sequence and MoRFs of the training set.RESULTS: We evaluated the performance of our predictor by comparing its results with those of two currently available MoRF predictors, MoRFpred and ANCHOR. Using three test sets that have previously been collected and used to evaluate MoRFpred and ANCHOR, we demonstrate that MoRFCHiBi outperforms the other predictors with respect to different evaluation metrics. In addition, MoRFCHiBi is downloadable and fast, which makes it useful as a component in other computational prediction tools.AVAILABILITY AND IMPLEMENTATION: http://www.chibi.ubc.ca/morf/., OPAL: prediction of MoRF regions in intrinsically disordered protein sequences.Supplementary data are available at Bioinformatics online., Computational prediction of MoRFs helps identify the potentially functional regions in IDRs.[SEP]Relations: response to amino acid has relations: bioprocess_protein with CASP3, bioprocess_protein with CASP3, bioprocess_protein with GIP, bioprocess_protein with GIP, bioprocess_protein with ALAD, bioprocess_protein with ALAD, bioprocess_protein with ARG1, bioprocess_protein with ARG1, bioprocess_protein with GLRB, bioprocess_protein with GLRB. Definitions: proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. Protein Sequences defined as following: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.. SVMT defined as following: Human SLC18A2 wild-type allele is located in the vicinity of 10q25 and is approximately 38 kb in length. This allele, which encodes synaptic vesicular amine transporter protein, is involved in the subcellular localization of neurotransmitters.. HSE defined as following: An acute (or rarely chronic) inflammatory process of the brain caused by SIMPLEXVIRUS infections which may be fatal. The majority of infections are caused by human herpesvirus 1 (HERPESVIRUS 1, HUMAN) and less often by human herpesvirus 2 (HERPESVIRUS 2, HUMAN). Clinical manifestations include FEVER; HEADACHE; SEIZURES; HALLUCINATIONS; behavioral alterations; APHASIA; hemiparesis; and COMA. Pathologically, the condition is marked by a hemorrhagic necrosis involving the medial and inferior TEMPORAL LOBE and orbital regions of the FRONTAL LOBE. (From Adams et al., Principles of Neurology, 6th ed, pp751-4). residue defined as following: A single unit within a polymer; a recognizable molecular fragment embedded in a larger molecule.. ANCHOR defined as following: A 25-item self-report questionnaire that utilizes a five-point rating scale to assess the physical and psychological symptoms and physical impact of anal cancer experienced in the past seven days.. MoRF defined as following: Human KAT6B wild-type allele is located in the vicinity of 10q22.2 and is approximately 207 kb in length. This allele, which encodes histone acetyltransferase KAT6B protein, is involved in the modulation of both histone acetylation and transcriptional activation. A chromosomal aberration involving the gene and the CREBBP gene, translocation t(10;16)(q22;p13), is associated with acute myeloid leukemias..", "label": "yes"} {"id": "converted_4667", "sentence1": "Is Ameloblastoma (AB) a common benign tumor occurring in the brain?", "sentence2": "Ameloblastoma is a benign odontogenic tumor which undergoes malignant transformation to ameloblastic carcinoma. , Ameloblastomas are benign tumors that most commonly affecting the mandible. , Ameloblastoma is a neoplasm arising in the craniofacial skeleton., Ameloblastoma is an invasive odontogenic tumor, and for reconstruction, i, Ameloblastoma is a locally aggressive, benign epithelial odontogenic neoplasm currently classified to include conventional, unicystic, and extraosseous/peripheral subtypes. , Ameloblastoma (AM) is a slow growing and aggressive benign tumor with an odontogenic epithelial origin arising from the mandible or maxilla., The ameloblastoma is a benign but aggressive neoplasm of odontogenic origin., Ameloblastoma is a rare odontogenic tumor of the jaw., Ameloblastoma is the most common epithelial odontogenic tumor., Ameloblastoma or adamantinoma is the rarest of the three forms of tumor of the odontogenic type., Ameloblastoma is a benign locally invasive odontogenic tumor., Ameloblastoma is the second most common benign epithelial odontogenic tumor and though it is of a benign nature, it is locally invasive, has a high recurrence rate and could potentially become malignant., BACKGROUND: The ameloblastoma is the most common odontogenic epithelial tumor, which belong to benign neoplasms that present a painless course, and usually occur in the oromaxillo-facial region., Ameloblastoma is the most common odontogenic tumor of epithelial origin, and though it is of a benign nature, it frequently infiltrates the bone, has a high rate of recurrence and could potentially become malignant., OBJECTIVES: Ameloblastoma is a benign, slow-growing, locally invasive epithelial tumor of odontogenic origin, with unlimited growth capacity and a strong tendency to recur., Ameloblastoma, a benign but locally aggressive odontogenic tumor, often demonstrates metastasis despite benign histological features and this variant is termed as metastasizing ameloblastoma (METAM). , Ameloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic malignant neoplasm and the malignant counterpart of benign epithelial odontogenic tumor of ameloblastoma (AB) by the WHO classification. AC, BACKGROUND: The ameloblastoma is the most common odontogenic epithelial tumor, which belong to benign neoplasms that present a painless course, and usually occur in the oromaxillo-fac, Peripheral ameloblastoma is a benign odontogenic tumor with the same histological characteristics as the centrally located ameloblastoma, but appearing in the gingiva and mucosa of the tooth-bearing area of the jaws., BACKGROUND Ameloblastoma (AB) is a common odontogenic epithelial tumor, with locally invasive behavior and high recurrence., Ameloblastoma(AB) is an aggressive and slow-growing tumor with high recurrence rate, which arises from odontogenic epithelium., Ameloblastoma (AB) is the most common benign epithelial odontogenic tumor occurring in the jawbone., or growth. Ameloblastoma (AB) is a relatively common odontogenic epithelial neoplasm that manifests local infiltrative intraosse, Ameloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic malignant neoplasm and the malignant counterpart of benign epithelial odontogenic tumor of ameloblastoma (AB) by the WHO classification., Ameloblastoma is a benign epithelial odontogenic tumor that typically arises in the mandible or maxilla or, rarely, in the immediate adjacent soft tissues, nic epithelial components with a mature fibrous stroma. It is the second most common odontogenic neoplasm following odontome. Acanthomatous ameloblast, OBJECTIVE AND IMPORTANCE: Ameloblastoma is a locally aggressive benign tumor, commonly occurring in the mandible, BACKGROUND AND OVERVIEW: Ameloblastoma is an odontogenic tumor predominantly occurring in patients who are in their 20s and 30s, BACKGROUND: The ameloblastoma is the most common odontogenic epithelial tumor, which belong to benign neoplasms that present a painless course, and usually occur in the oromaxillo-facial region, BACKGROUND: Ameloblastoma is a neoplasm classified as a benign epithelial odontogenic tumor of the jaws, grow slowly and are locally invasive, BACKGROUND: Ameloblastoma is a frequent odontogenic benign tumor characterized by local invasiveness, high risk of recurrence and occasional metastasis and malignant transformation, BACKGROUND: Ameloblastoma is a rare benign odontogenic tumor with locally aggressive behavior and a high recurrence rate, BACKGROUND: Ameloblastoma is a benign odontogenic tumor, exhibiting local invasiveness and high rate of recurrence, BACKGROUND: Ameloblastoma is a rare benign odontogenic tumor with a metastasis rate estimated at 2% of cases, mainly involving the lung (80%) and lymph nodes (20%).METHODS: We hereby present the case of a 26 year old patient with a history of locally recurrent mandibular ameloblastoma who developed a temporal intracranial ameloblastoma tumor requiring a collaborative neurosurgical and maxillo-facial radical surgical approach.CONCLUSION: Although ameloblastomas are histologically benign, the temporal topography questions the dissemination pathophysiology of the tumor (metastasis or local extension through temporal muscle fibers), mainly relevant , Ameloblastoma is a histologically benign tumor derived from odontogenic apparatus., BACKGROUND: Ameloblastoma is a benign odontogenic tumour that may exhibit aggressive biological behaviour with local recurrence and metastasis following initial surgica, Ameloblastomas are histologically benign tumors derived from the odontogenic apparatus., Ameloblastoma is a benign odontogenic tumor generally present in the jaw bone., Ameloblastoma is a locally aggressive tumor derived from odontogenic epithelium., Ameloblastoma is the most common clinically significant epithelial odontogenic tumor, and is considered a benign but locally aggressive tumor of the craniofacial region., Ameloblastoma (AB), which is the most common odontogenic tumor, may originate from the dental lamina remnants.[SEP]Relations: ameloblastoma has relations: disease_disease with benign epithelial neoplasm, disease_disease with benign epithelial neoplasm, disease_disease with benign epithelial neoplasm, disease_disease with benign epithelial neoplasm, disease_disease with benign epithelial neoplasm, disease_disease with benign epithelial neoplasm, disease_disease with bone ameloblastoma, disease_disease with bone ameloblastoma, disease_disease with bone ameloblastoma, disease_disease with bone ameloblastoma. Definitions: variant defined as following: An alteration or difference from a norm or standard.. Ameloblastic carcinoma defined as following: A rare, cytologically malignant ameloblastoma that may metastasize.. adamantinoma defined as following: A low grade malignant neoplasm arising from the long bones. The tibia is the most frequently affected bone site. Patients present with swelling which may or may not be associated with pain. Morphologically, it is characterized by a biphasic pattern consisting of an epithelial and an osteofibrous component. The vast majority of cases recur if they are not treated with radical surgery. In a minority of cases the tumor may metastasize to other anatomic sites including lymph nodes, lungs, liver, brain, and skeleton.. Ameloblastoma defined as following: An immature epithelial tumor of the JAW originating from the epithelial rests of Malassez or from other epithelial remnants of the ENAMEL from the developmental period. It is a slowly growing tumor, usually benign, but displays a marked propensity for invasive growth.. benign odontogenic tumour defined as following: A benign, slow growing neoplasm arising from tooth-forming tissues. It occurs in the maxillofacial skeleton or the gingiva. Representative examples include adenomatoid odontogenic tumor, calcifying cystic odontogenic tumor, and squamous odontogenic tumor.. benign tumors defined as following: A neoplasm which is characterized by the absence of morphologic features associated with malignancy (severe cytologic atypia, tumor cell necrosis, and high mitotic rate). Benign neoplasms remain confined to the original site of growth and do not metastasize to other anatomic sites.. jaw bone defined as following: Bony structure of the mouth that holds the teeth. It consists of the MANDIBLE and the MAXILLA.. maxilla defined as following: One of a pair of irregularly shaped bones that form the upper jaw. A maxillary bone provides tooth sockets for the superior teeth, forms part of the ORBIT, and contains the MAXILLARY SINUS.. odontogenic neoplasm defined as following: Neoplasms produced from tooth-forming tissues.. neoplasm defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. soft tissues defined as following: A general term comprising tissue that is not hardened or calcified; including muscle, fat, blood vessels, nerves, tendons, ligaments and fascia.. aggressive behavior defined as following: Behavior which may be manifested by destructive and attacking action which is verbal or physical, by covert attitudes of hostility or by obstructionism.. metastasizing ameloblastoma defined as following: A rare, well differentiated, cytologically benign ameloblastoma which paradoxically metastasizes.. benign tumor defined as following: A neoplasm which is characterized by the absence of morphologic features associated with malignancy (severe cytologic atypia, tumor cell necrosis, and high mitotic rate). Benign neoplasms remain confined to the original site of growth and do not metastasize to other anatomic sites..", "label": "no"} {"id": "converted_4631", "sentence1": "Is taxilin a cancer marker?", "sentence2": "Αlpha-Taxilin (α-Taxilin) has been found as one of the novel, significantly up regulated protein in RA, Expression of α-taxilin has been implicated in the development of human glioblastoma, hepatocellular carcinoma and renal cell carcinoma. , α-Taxilin, a binding partner of the syntaxin family, is a candidate tumor marker. , Expression of α-taxilin in hepatocellular carcinoma correlates with growth activity and malignant potential of the tumor.[SEP]Relations: Clear cell renal cell carcinoma has relations: disease_phenotype_positive with Blau syndrome, disease_phenotype_positive with Blau syndrome, disease_phenotype_positive with renal cell carcinoma (disease), disease_phenotype_positive with renal cell carcinoma (disease). liver carcinoma in situ has relations: disease_disease with in situ carcinoma, disease_disease with in situ carcinoma, disease_disease with bile duct carcinoma in situ, disease_disease with bile duct carcinoma in situ, disease_disease with carcinoma of liver and intrahepatic biliary tract, disease_disease with carcinoma of liver and intrahepatic biliary tract. Definitions: glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO). renal cell carcinoma defined as following: A malignant epithelial neoplasm of the kidney characterized by the presence of lipid-containing clear cells within a vascular network. The tumor may metastasize to unusual sites and late metastasis is common.. human defined as following: Members of the species Homo sapiens.. hepatocellular carcinoma defined as following: A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.. RA defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. taxilin defined as following: Alpha-taxilin (546 aa, ~62 kDa) is encoded by the human TXLNA gene. This protein is involved in vesicular trafficking..", "label": "yes"} {"id": "converted_1134", "sentence1": "Are Drosophila ultraconserved elements candidate ncRNAs?", "sentence2": "Highly constrained intergenic Drosophila ultraconserved elements are candidate ncRNAs., Here, we report the discovery and characterization of UCEs from 12 sequenced Drosophila species. We identified 98 elements ≥80 bp long with very high conservation across the Drosophila phylogeny. Population genetic analyses reveal that these UCEs are not present in mutational cold spots. Instead we infer that they experience a level of selective constraint almost 10-fold higher compared with missense mutations in protein-coding sequences, which is substantially higher than that observed previously for human UCEs. About one-half of these Drosophila UCEs overlap the transcribed portion of genes, with many of those that are within coding sequences likely to correspond to sites of ADAR-dependent RNA editing. For the remaining UCEs that are in nongenic regions, we find that many are potentially capable of forming RNA secondary structures. Among ten chosen for further analysis, we discovered that the majority are transcribed in multiple tissues of Drosophila melanogaster. We conclude that Drosophila species are rich with UCEs and that many of them may correspond to novel noncoding RNAs., Highly Constrained Intergenic Drosophila Ultraconserved Elements Are Candidate ncRNAs[SEP]Definitions: conservation defined as following: The maintenance of certain characteristics in an unchanged condition..", "label": "yes"} {"id": "converted_3736", "sentence1": "Is αCGRP a member of the CGRP family?", "sentence2": "αCGRP, another amyloidogenic member of the CGRP family., Therefore, in this work, we investigated the amyloidogenic profile of αCGRP, a 37-residue-long peptide hormone, utilizing both biophysical experimental techniques and Molecular Dynamics simulations. These efforts unravel a novel amyloidogenic member of the CGRP family and provide insights into the mechanism underlying the αCGRP polymerization., These efforts unravel a novel amyloidogenic member of the CGRP family and provide insights into the mechanism underlying the αCGRP polymerization., These efforts unravel a novel amyloidogenic member of the CGRP family and provide insights into the mechanism underlying the αCGRP polymerization.[SEP]Relations: neuropeptide hormone activity has relations: molfunc_protein with GRP, molfunc_protein with GRP, molfunc_protein with AGRP, molfunc_protein with AGRP, molfunc_protein with CCK, molfunc_protein with CCK, molfunc_protein with QRFP, molfunc_protein with QRFP, molfunc_protein with PRLH, molfunc_protein with PRLH. Definitions: CGRP defined as following: A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.. peptide hormone defined as following: OBSOLETE. (Was not defined before being made obsolete). [GOC:ai].", "label": "yes"} {"id": "converted_1237", "sentence1": "Has the protein GFP been used in transgenesis for live protein imaging?", "sentence2": "we review recent advancement in the functional studies of the three different GnRH neuron systems, mainly focusing on the electrophysiological analysis of the GnRH-green fluorescent protein (GFP) transgenic animals., founders were found to be transgenic for GFP., GFP expression was detected in a wide range of murine tissues, Transgenic Xenopus laevis for live imaging in cell and developmental biology., The stable transgenesis of genes encoding functional or spatially localized proteins, fused to fluorescent proteins such as green fluorescent protein (GFP) or red fluorescent protein (RFP), is an extremely important research tool in cell and developmental biology., GFP-transgenic animals for in vivo imaging: rats, rabbits, and pigs., We have further extended the techniques of genetic engineering to rats, rabbits, and pigs, and have created corresponding GFP-transgenic animals., The results revealed that the 3.6-GFP transgenic animals provide a unique model for direct analysis of cellular and molecular mechanisms of pulp repair and tertiary dentinogenesis in vivo., Long-term effects of PERV-specific RNA interference in transgenic pigs., green fluorescent protein (GFP) as reporter of the vector system were consistently expressed in transgenic animals., The ability to specify the expression levels of exogenous genes inserted in the genomes of transgenic animals is critical for the success of a wide variety of experimental manipulations. , Welfare assessment in transgenic pigs expressing green fluorescent protein (GFP)., transgenic animals expressing GFP with wildtype animals along various stages of post natal development, Production of transgenic chickens expressing a tetracycline-inducible GFP gene., transgenic animals can be readily created to express fluorescently tagged proteins or reporters, These findings suggest that mhc2dab:GFP and cd45:DsRed transgenic lines will be instrumental in elucidating the immune response in the zebrafish., f 33 mice born, 28 (81%) carried the transgene DNA and 15 (55.5%) were GFP-positive., Lentiviral vectors containing the green fluorescent protein gene have been successfully used to select transgenic embryos before transfer to a surrogate mother, Typically transgenes are generated by placing a promoter upstream of a GFP reporter gene or cDNA of interest, and this often produces a representative expression pattern., Survival and immunogenicity of mesenchymal stem cells from the green fluorescent protein transgenic rat in the adult rat brain., This problem has been lessened by the availability of transgenic animals that express \"reporter\" genes, such as green fluorescent protein (GFP), full-length GFP fusion proteins was examined, in transgenic animals, , Two stable transgenic lines express GFP prior to hair-bundle formation, we generated two transgenic pigs by somatic cell nuclear transfer (SCNT) that express green fluorescent protein (GFP) driven by cytomegalovirus (CMV)., Fluorescent proteins such as the green fluorescent protein (GFP) have widely been used in transgenic animals as reporter genes. , Green Fluorescent Protein (GFP) is used extensively as a reporter for transgene expression in Drosophila and other organisms.[SEP]Relations: Animal protein allergy has relations: phenotype_phenotype with Allergy, phenotype_phenotype with Allergy, phenotype_phenotype with Animal dander allergy, phenotype_phenotype with Animal dander allergy. lymphocyte anergy has relations: bioprocess_bioprocess with tolerance induction, bioprocess_bioprocess with tolerance induction, bioprocess_bioprocess with B cell anergy, bioprocess_bioprocess with B cell anergy, bioprocess_bioprocess with T cell anergy, bioprocess_bioprocess with T cell anergy. Definitions: mesenchymal stem cells defined as following: An undifferentiated stromal cell with the ability to develop into the cells that form distinct mesenchymal tissues; such as bone, muscle, connective tissue, blood vessels, and lymphatic tissue.. transgenic animals defined as following: Experimental organism whose genome has been altered by the transfer of a gene or genes from another species or breed.. pulp defined as following: A richly vascularized and innervated connective tissue of mesodermal origin, contained in the central cavity of a tooth and delimited by the dentin, and having formative, nutritive, sensory, and protective functions. (Jablonski, Dictionary of Dentistry, 1992). rabbits defined as following: Taxonomic family which includes rabbits and hares.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. green fluorescent protein defined as following: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.. cDNA defined as following: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.. zebrafish defined as following: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research.. cellular defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. transgenes defined as following: Genes that are introduced into an organism using GENE TRANSFER TECHNIQUES.. genomes defined as following: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.. RFP defined as following: Zinc finger protein RFP (513 aa, ~58 kDa) is encoded by the human TRIM27 gene. This protein is involved in the modulation of both gene transcription and apoptosis.. reporter genes defined as following: Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.. murine defined as following: Any of numerous species of small rodents belonging to the genus Mus and various related genera of the family Muridae.. organisms defined as following: A living entity.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. GFP defined as following: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species..", "label": "yes"} {"id": "converted_167", "sentence1": "Is CD84 genetically associated with arthritis?", "sentence2": "The SNP is predicted to disrupt transcription factor binding site motifs in the 3' UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1 × 10(-11) in 228 non-RA patients and P = 0.004 in 132 RA patients), Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity, Three members of this gene family, Ly108, Ly9, and CD84, exhibit polymorphisms that strongly influence susceptibility to systemic autoimmunity, notably in mice, but also in some human populations[SEP]Relations: Rheumatoid arthritis has relations: disease_phenotype_positive with IgG4-related retroperitoneal fibrosis, disease_phenotype_positive with IgG4-related retroperitoneal fibrosis, disease_phenotype_positive with hereditary xanthinuria, disease_phenotype_positive with hereditary xanthinuria, phenotype_phenotype with Arthritis, phenotype_phenotype with Arthritis, drug_effect with Interferon alfa-2b, drug_effect with Interferon alfa-2b, disease_phenotype_positive with achalasia (disease), disease_phenotype_positive with achalasia (disease). Definitions: peripheral blood mononuclear cells defined as following: A peripheral blood cell with a single nucleus. This category includes lymphocytes and monocytes.. Ly108 defined as following: Human SLAMF6 wild-type allele is located in the vicinity of 1q23.2 and is approximately 38 kb in length. This allele, which encodes SLAM family member 6 protein, plays a role as a coreceptor in natural killer cell activation.. Ly9 defined as following: T-lymphocyte surface antigen Ly-9 (655 aa, ~72 kDa) is encoded by the human LY9 gene. This protein is involved in the positive regulation of helper T-cell Th17 differentiation.. allele defined as following: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.. human defined as following: Members of the species Homo sapiens.. RA defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. 3' UTR defined as following: The sequence at the 3' end of messenger RNA that does not code for product. This region contains transcription and translation regulating sequences.. polymorphisms defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.. SNP defined as following: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.. etanercept defined as following: A recombinant version of soluble human TNF receptor fused to an IgG FC fragment that binds specifically to TUMOR NECROSIS FACTOR and inhibits its binding with endogenous TNF receptors. It prevents the inflammatory effect of TNF and is used to treat RHEUMATOID ARTHRITIS; PSORIATIC ARTHRITIS and ANKYLOSING SPONDYLITIS.. arthritis defined as following: Acute or chronic inflammation of JOINTS..", "label": "yes"} {"id": "converted_3173", "sentence1": "Can prevnar 13 be used in children?", "sentence2": "PCV13 is approved for routine vaccination of all infants as a 4-dose series at age 2, 4, 6, and 12-15 months for children who previously received 1 or more doses of the 7-valent pneumococcal conjugate vaccine (PCV7), and for children with underlying medical conditions that increase their risk for pneumococcal disease or its complications. , Based on published immunogenicity and safety data, as well as the recent recommendations by the ACIP for routine use in infants and indications for high-risk pediatric patients, PCV13 is a revised formulation of pneumococcal vaccine that should be included on pharmacy formularies., To review the immunogenicity, efficacy, and safety of the 13-valent pneumococcal conjugate vaccine (PCV13) for use in pediatric patients.[SEP]", "label": "yes"} {"id": "converted_3074", "sentence1": "Has strimvelis been approved by the European Medicines Agency?", "sentence2": "Strimvelis (autologous CD34+ cells transduced to express adenosine deaminase [ADA]) is the first ex vivo stem cell gene therapy approved by the European Medicines Agency (EMA), indicated as a single treatment for patients with ADA-severe combined immunodeficiency (ADA-SCID) who lack a suitable matched related bone marrow donor. [SEP]Relations: cellular response to stem cell factor stimulus has relations: bioprocess_bioprocess with cellular response to cytokine stimulus, bioprocess_bioprocess with cellular response to cytokine stimulus. severe combined immunodeficiency due to LAT deficiency has relations: disease_phenotype_positive with Immune dysregulation, disease_phenotype_positive with Immune dysregulation, disease_phenotype_positive with Splenomegaly, disease_phenotype_positive with Splenomegaly. multiple acyl-CoA dehydrogenase deficiency has relations: disease_phenotype_positive with Lacticaciduria, disease_phenotype_positive with Lacticaciduria, disease_phenotype_positive with Cardiorespiratory arrest, disease_phenotype_positive with Cardiorespiratory arrest. Definitions: ADA-SCID defined as following: Severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency is a form of SCID characterized by profound lymphopenia and very low immunoglobulin levels of all isotypes resulting in severe and recurrent opportunistic infections.. adenosine deaminase defined as following: This gene is involved in nucleotide metabolism and cellular immunity.. EMA defined as following: An autosomal recessive disorder of fatty acid oxidation, and branched chain amino acids (AMINO ACIDS, BRANCHED-CHAIN); LYSINE; and CHOLINE catabolism, that is due to defects in either subunit of ELECTRON TRANSFER FLAVOPROTEIN or its dehydrogenase, electron transfer flavoprotein-ubiquinone oxidoreductase (EC 1.5.5.1).. stem cell defined as following: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.. ADA defined as following: Catalysis of the reaction: acetaldehyde + CoA + NAD+ = acetyl-CoA + NADH + H+. [EC:1.2.1.10].", "label": "yes"} {"id": "converted_1260", "sentence1": "Was tamoxifen tested for treatment of glioma patients?", "sentence2": "Tamoxifen might have a role in the initial treatment of high-grade gliomas and should be studied in future Phase II trials building on the newly established platform of concurrent chemoradiotherapy., The addition of high-dose tamoxifen to standard radiotherapy does not improve the survival of patients with diffuse intrinsic pontine glioma., In this study, in which tamoxifen was used in conjunction with radiotherapy, progression free survival was shown to be less good when compared with historical data HR = 3.1 (CI: 1.7-5.7)., The addition of high-dose tamoxifen, although well tolerated, confers no clinical benefit to patients treated with diffuse intrinsic pontine glioma treated with standard radiotherapy., CONCLUSIONS: Carboplatin and high dose tamoxifen has similar response rates to other regimens for recurrent malignant gliomas and are probably equivalent to those found using tamoxifen as monotherapy. , CONCLUSIONS: Pegylated liposomal doxorubicin administered alone or in combination with tamoxifen is safe and moderately effective in patients with recurrent high-grade glioma., Protein kinase C (PKC) inhibitors such as high-dose tamoxifen and hypericin also have been used in the treatment of malignant gliomas. , Considering these facts, polyethylene-glycol-liposomal doxorubicin with and without tamoxifen was evaluated within two sequential Phase II trials performed at our institution. , In a parallel phase-II-study investigating post-operative treatment with tamoxifen (TAM), carboplatin and radiation therapy for glioblastomas, 16 of 49 patients (33%) showed multifocal recurrence, which developed after a mean of 46 weeks, raising the question of an association with therapy., Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study. Brainstem Glioma Cooperative Group., PURPOSE: The efficacy of radiation therapy (RT) combined with tamoxifen (TX) was tested in patients diagnosed with diffuse brainstem gliomas in a multicenter trial., CONCLUSION: This treatment combination produced no significant change in the overall poor prognosis of these patients. Most tumors responded initially to treatment but recurred as the study progressed. A minority of patients seemed to benefit from the extended use of TX. , Tamoxifen, a protein kinase C inhibitor when administered in high dosages, is currently being used as an adjuvant in the treatment of patients with malignant gliomas., We present a patient with a recurrent malignant glioma who was continued on high dose tamoxifen despite radiologic documented doubling of the tumor size and who eventually showed a delayed response to this agent nine months after initiation of treatment., The combination of oral tamoxifen (120 to 240 mg/m2/day) and subcutaneous interferon-alpha [6 x 10(6) U three times per week] was associated with significant neurotoxicity in this group of recurrent glioma patients, resulting in early study closure., A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood., Phase I clinical trial assessing temozolomide and tamoxifen with concomitant radiotherapy for treatment of high-grade glioma., Prolonged treatment with biologic agents for malignant glioma: a case study with high dose tamoxifen., Tamoxifen as a potential treatment of glioma., We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial. , PURPOSE: The efficacy of radiation therapy (RT) combined with tamoxifen (TX) was tested in patients diagnosed with diffuse brainstem gliomas in a multicenter trial. , We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial., The efficacy of radiation therapy (RT) combined with tamoxifen (TX) was tested in patients diagnosed with diffuse brainstem gliomas in a multicenter trial., The efficacy of radiation therapy (RT) combined with tamoxifen (TX) was tested in patients diagnosed with diffuse brainstem gliomas in a multicenter trial., We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial. Eligible patients had radiographically measurable recurrent gliomas of any grade after initial radiation therapy., Thyroid function was suppressed to reduce IGF-1 levels in glioma patients and high-dose tamoxifen administered. Propylthiouracil was used to induce chemical hypothyroidism in 22 patients with recurrent glioma., Activity against recurrent gliomas has been reported for both tamoxifen and interferon alpha, agents that have more acceptable toxicity profiles and that can be administered in an outpatient setting. We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial., Thyroid function was suppressed to reduce IGF-1 levels in glioma patients and high-dose tamoxifen administered., Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study., We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial., The subsequent in vitro testing of the tumor that was removed after the recurrence of tumor (22 months after the initiation of tamoxifen) revealed loss of sensitivity to tamoxifen., The combination of oral tamoxifen (120 to 240 mg/m2/day) and subcutaneous interferon-alpha [6 x 10(6) U three times per week] was associated with significant neurotoxicity in this group of recurrent glioma patients, resulting in early study closure.[SEP]Relations: Tamoxifen has relations: drug_effect with Lymphedema, drug_effect with Lymphedema, drug_drug with Glisoxepide, drug_drug with Glisoxepide, drug_drug with Glyburide, drug_drug with Glyburide, drug_effect with Erythema, drug_effect with Erythema, drug_effect with Edema, drug_effect with Edema. Definitions: malignant glioma defined as following: A grade 3 or grade 4 glioma arising from the central nervous system. This category includes glioblastoma, anaplastic astrocytoma, anaplastic ependymoma, anaplastic oligodendroglioma, and anaplastic oligoastrocytoma.. PKC defined as following: Paroxysmal kinesigenic dyskinesia (PKD) is a form of paroxysmal dyskinesia (see this term), characterized by recurrent brief involuntary hyperkinesias, such as choreoathetosis, ballism, athetosis or dystonia, triggered by sudden movements.. carboplatin defined as following: An organoplatinum compound that possesses antineoplastic activity.. protein kinase C defined as following: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.. Tamoxifen defined as following: One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.. gliomas defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21). biologic agents defined as following: Endogenously synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.. IGF-1 defined as following: A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.. doxorubicin defined as following: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.. hypericin defined as following: An anthraquinone derivative that is naturally found in the yellow flower of Hypericum perforatum (St. John's wort) with antidepressant, potential antiviral, antineoplastic and immunostimulating activities. Hypericin appears to inhibit the neuronal uptake of serotonin, norepinephrine, dopamine, gamma-amino butyric acid (GABA) and L-glutamate, which may contribute to its antidepressant effect. Hypericin may also prevent the replication of encapsulated viruses probably due to inhibition of the assembly and shedding of virus particles in infected cells. This agent also exerts potent phototoxic effects by triggering apoptotic signaling that results in formation of reactive oxygen species.. glioblastomas defined as following: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.. temozolomide defined as following: A dacarbazine derivative that is used as an alkylating antineoplastic agent for the treatment of MALIGNANT GLIOMA and MALIGNANT MELANOMA.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. neurotoxicity defined as following: Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. TAM defined as following: A conserved AMINO ACID SEQUENCE located in the intracellular domains of a family of transmembrane proteins involved in various IMMUNE RESPONSES. The CONSENSUS SEQUENCE of this motif is YXXL(or I)X(6-8)YXXL(or I) (where X denotes any amino acid). When phosphorylated ITAM motifs provide docking sites for PROTEIN TYROSINE KINASES of the Syk family thus forming signaling complexes which lead to activation of immune responses.. Propylthiouracil defined as following: A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534). tamoxifen defined as following: One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM..", "label": "yes"} {"id": "converted_4238", "sentence1": "Does daily atemoya juice intake change the pharmacokinetics of CYP1A2 substrates?", "sentence2": "Atemoya juice significantly inhibited CYP1A2 activity in human liver microsomes, but not the activities of CYP2C9 and CYP3A. In spite of this inhibition, preadministration of atemoya had no effect on the pharmacokinetics of phenacetin, a CYP1A2 substrate, in rats. , The results indicate that a daily intake of atemoya would not change the pharmacokinetics of CYP1A2 substrates such as phenacetin as well as CYP2C9- and CYP3A-substrate drugs.[SEP]Relations: Phenacetin has relations: drug_protein with CYP1A2, drug_protein with CYP1A2, drug_protein with CYP2A6, drug_protein with CYP2A6, drug_protein with CYP2E1, drug_protein with CYP2E1, drug_drug with Atenolol, drug_drug with Atenolol, drug_protein with CYP2A13, drug_protein with CYP2A13. Definitions: CYP2C9 defined as following: A cytochrome P-450 subtype that has specificity for acidic XENOBIOTICS. It oxidizes a broad range of important clinical drugs that fall under the categories of NONSTEROIDAL ANTI-INFLAMMATORY AGENTS; HYPOGLYCEMIC AGENTS; ANTCOAGULANTS; and DIURETICS.. phenacetin defined as following: A phenylacetamide that was formerly used in ANALGESICS but nephropathy and METHEMOGLOBINEMIA led to its withdrawal from the market. (From Smith and Reynard, Textbook of Pharmacology,1991, p431). rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. CYP3A defined as following: A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.. human defined as following: Members of the species Homo sapiens.. CYP1A2 substrates defined as following: Any substance acted upon by cytochrome P450 1A2..", "label": "no"} {"id": "converted_1599", "sentence1": "Is there any protein that undergoes both mono-ubiquitination and poly-ubiquitination?", "sentence2": "The yeast G protein alpha subunit Gpa1 represents a rare example of a protein that undergoes both mono- and poly-ubiquitination. , Expression of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation, whereas p34 knockdown results in PTEN mono-ubiquitination., These fingers possess E3 activities of mono-ubiquitination and poly-ubiquitination, respectively, with ubiquitin-conjugating enzyme (E2)-binding capabilities. , Instead of promoting poly-ubiquitination and degradation, we show that Smurf2 actually induces multiple mono-ubiquitination of Smad3 in vivo., mono-ubiquitination of CIITA dramatically increases its transactivity whereas poly-ubiquitination leads to CIITA degradation., This leads to a model in which Lys134 of LDB1 can be either mono-ubiquitinated, leading to stabilization, or poly-ubiquitinated, leading to degradation by the proteasome pathway. , mono-ubiquitination of CIITA increases its transactivity, whereas poly-ubiquitination of CIITA leads to its degradation, PS1 ubiquitination after PI3K inhibition is represented by the multiple mono-ubiquitination, instead of poly-ubiquitination, Our observations support a novel functional relationship between parkin and Hsc/Hsp70 and support the notion that parkin is a multi-purpose E3 ubiquitin ligase capable of modifying proteins either via attachment of alternatively linked poly-ubiquitin chains or through multiple mono-ubiquitination to achieve alternate biological outcomes, our results indicate that Hsp70 facilitates CHIP-mediated poly-ubiquitination of Smad1 whereas it attenuates CHIP-meditated mono-ubiquitination of Smad1., Whereas poly-ubiquitination targets protein substrates for proteasomal degradation, mono-ubiquitination is known to regulate protein trafficking in the endosomal system and to target cargo proteins for lysosomal degradation., Our results suggest that oxidative stress induces not only poly-ubiquitination but also mono-ubiquitination of LDH-A, which may be involved in its lysosomal degradation during unloading., wild type Smad4 is a relatively stable protein that undergoes mono- or oligo-ubiquitination, a modification not linked to protein degradation, These data suggest that oligo-ubiquitination positively regulates Smad4 function, whereas poly-ubiquitination primarily occurs in unstable cancer mutants and leads to protein degradation., We found that Ro52 was strongly conjugated by a single molecule of ubiquitin in cells. Although the biological relevance of this mono-ubiquitination was not defined, the function of Ro52 might be modified by the mono-ubiquitination. We also found that Ro52 was conjugated with poly-ubiquitin chain in cells (poly-ubiquitination)[SEP]Relations: E3 ubiquitin ligases ubiquitinate target proteins has relations: pathway_protein with WAC, pathway_protein with WAC, pathway_protein with UBA52, pathway_protein with UBA52, pathway_protein with PAF1, pathway_protein with PAF1, pathway_protein with PEX2, pathway_protein with PEX2, pathway_protein with H2BC6, pathway_protein with H2BC6. Definitions: Ro52 defined as following: This gene is involved in the modulation of protein ubiquitination.. LDH-A defined as following: A member of the LACTATE DEHYDROGENASES isozyme family, Lactate Dehydrogenase 5 is localized to liver and skeletal muscle cells where its expression increases in liver disease and striated muscle trauma respectively.. Gpa1 defined as following: This gene plays a role in protein hormone signaling.. CIITA defined as following: MHC class II transactivator (1130 aa, ~123 kDa) is encoded by the human CIITA gene. This protein plays a role in the expression of HLA class II genes.. Smad3 defined as following: Mothers against decapentaplegic homolog 3 (425 aa, ~48 kDa) is encoded by the human SMAD3 gene. This protein plays a role in the modulation of transforming growth factor (TGF)-beta-mediated signaling and gene expression.. PTEN defined as following: Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (403 aa, ~47 kDa) is encoded by the human PTEN gene. This protein plays a role in signaling and as both a dual-specificity phosphoprotein phosphatase and a lipid phosphatase.. PTEN protein defined as following: A lipid phosphatase that contains a C2 DOMAIN and acts on phosphatidylinositol-3,4,5-trisphosphate to regulate various SIGNAL TRANSDUCTION PATHWAYS. It modulates CELL GROWTH PROCESSES; CELL MIGRATION; and APOPTOSIS. Mutations in PTEN are associated with COWDEN DISEASE and PROTEUS SYNDROME as well as NEOPLASTIC CELL TRANSFORMATION.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. Smurf2 defined as following: E3 ubiquitin-protein ligase SMURF2 (748 aa, ~86 kDa) is encoded by the human SMURF2 gene. This protein is involved in the modulation of SMAD/TGF-beta receptor complex degradation.. Smad4 defined as following: Mothers against decapentaplegic homolog 4 (552 aa, ~60 kDa) is encoded by the human SMAD4 gene. This protein is involved in cytokine signaling and transcription factor activity.. LDB1 defined as following: Human LDB2 wild-type allele is located in the vicinity of 4p16 and is approximately 397 kb in length. This allele, which encodes LIM domain-binding protein 2, plays a role in the modulation of gene transcription.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. mutants defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. cancer defined as following: A malignant tumor at the original site of growth.. Hsp70 defined as following: A family of structurally related proteins that are involved in both protein folding and cellular stress responses. The members of this family are approximately 70 kDa.. parkin defined as following: E3 ubiquitin-protein ligase parkin (465 aa, ~52 kDa) is encoded by the human PRKN gene. This protein may play a role in the ubiquitination of proteins targeted for proteasomal degradation.. p34 defined as following: This gene is involved in both transcription and repair of DNA.. Smad1 defined as following: Human GARS1 wild-type allele is located in the vicinity of 7p14.3 and is approximately 39 kb in length. This allele, which encodes glycine-tRNA ligase protein, is involved in the synthesis of glycyl-tRNA. Mutation of the gene is associated with type 2D Charcot-Marie-Tooth disease and distal hereditary motor neuropathy, type Va.. modification defined as following:Respond with exceptions, completions and modifications or revisions done before completion
. PS1 defined as following: Human PSEN1 wild-type allele is located in the vicinity of 14q24.3 and is approximately 87 kb in length. This allele, which encodes presenilin-1 protein, is involved in the modulation of proteolytic processing. Mutation of the gene is associated with early-onset Alzheimer disease and frontotemporal dementia.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary..", "label": "yes"} {"id": "converted_2245", "sentence1": "Is there a sequence bias in MNase digestion patterns?", "sentence2": "In addition, unlike MNase, MPE-Fe(II) cleaves nuclear DNA with little sequence bias., These findings collectively indicate that MPE-seq provides a unique and straightforward means for the genome-wide analysis of chromatin structure with minimal DNA sequence bias., Micrococcal nuclease does not substantially bias nucleosome mapping., MNase has hitherto been very widely used to map nucleosomes, although concerns have been raised over its potential to introduce bias., These results indicate that biases in nucleosome positioning data collected using MNase are, under our conditions, not significant., Signal variation in these simulations reveals an important DNA sampling bias that results from a neighborhood effect of MNase digestion techniques., Standardized collection of MNase-seq experiments enables unbiased dataset comparisons., Here, we show that the cutting preference of MNase in combination with size selection generates a sequence-dependent bias in the resulting fragments., We propose that combined MNase/exoIII digestion can be applied to in situ chromatin for unbiased genome-wide mapping of nucleosome positions that is not influenced by DNA sequences at the core/linker junctions., Signal variation in these simulations reveals an important DNA sampling bias that results from a neighborhood effect of MNase digestion techniques., Signal variation in these simulations reveals an important DNA sampling bias that results from a neighborhood effect of MNase digestion techniques., These results indicate that biases in nucleosome positioning data collected using MNase are, under our conditions, not significant.., Micrococcal nuclease does not substantially bias nucleosome mapping., We find that maize MNase-hypersensitive (MNase HS) regions localize around active genes and within recombination hotspots, focusing biased gene conversion at their flanks.[SEP]Relations: nucleosome mobilization has relations: bioprocess_protein with BPTF, bioprocess_protein with BPTF, bioprocess_protein with POLE3, bioprocess_protein with POLE3, bioprocess_protein with INO80, bioprocess_protein with INO80, bioprocess_protein with ARID1A, bioprocess_protein with ARID1A, bioprocess_bioprocess with chromatin remodeling, bioprocess_bioprocess with chromatin remodeling. Definitions: DNA sequences defined as following: The sequence of nucleotide residues along a DNA chain.. Micrococcal nuclease defined as following: An enzyme that catalyzes the endonucleolytic cleavage to 3'-phosphomononucleotide and 3'-phospholigonucleotide end-products. It can cause hydrolysis of double- or single-stranded DNA or RNA. (From Enzyme Nomenclature, 1992) EC 3.1.31.1.. nucleosome defined as following: A complex comprised of DNA wound around a multisubunit core and associated proteins, which forms the primary packing unit of DNA into higher order structures. [GOC:elh]. nuclear DNA defined as following: The DNA that is normally located in the nucleus of a eukaryotic cell.. nucleosomes defined as following: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4..", "label": "yes"} {"id": "converted_1585", "sentence1": "Can Preimplantation Genetic Diagnosis (PGD) be used for gender selection?", "sentence2": "This testing is used for identifying singlegene disorders, chromosomal abnormalities, mitochondrial disorders, gender selection in non-mendelian disorders with unequal gender distribution, aneuploidy screening, and other preconceptually identified genetic abnormalities in prospective parents. , Although many clinics offer PGD for HA by gender selection, an approach that detects the presence of the underlying F8 mutation has several advantages. , Preimplantation genetic diagnosis (PGD) for gender selection for non-medical reasons has been considered an unethical procedure by several authors and agencies in the Western society on the basis that it could disrupt the sex ratio, that it discriminates against women and that it leads to disposal of normal embryos of the non-desired gender. In this study, the analysis of a large series of PGD procedures for gender selection from a wide geographical area in the USA shows that, in general, there is no deviation in preference towards any specific gender except for a preference of males in some ethnic populations of Chinese, Indian and Middle Eastern origin that represent a small percentage of the US population. , In response to one specific question, one-third of the couples agreed to use the donor child as a lifetime organ donor and supported the use of PGD for non-medical gender selection. , More specifically, I illustrate how the prescriptions of deliberative democracy can be applied to the issue of regulating non-medical uses of pre-implantation genetic diagnosis (PGD), such as gender selection. , Private clinics were more likely than other programs to be on either the East or West Coast, list certain PGD risks (e.g., diagnostic error), note that PGD was new or controversial, reference source of PGD information, provide accuracy rates of genetic testing of embryos, and offer gender selection for social reasons., The purpose of this article is to ascertain and appraise the ethical issues inherent to the utilisation of preimplantation genetic diagnosis for gender selection in infertile patients anticipating undergoing a medically indicated assisted reproductive technique procedure. Performance of preimplantation genetic diagnosis per request specifically for gender selection by an infertile couple undergoing medically indicated assisted reproductive technique may not breach the principles of ethics, and is unlikely to alter the population balance of sexes., One possible use of PGD is to perform gender selection for couples whose offspring are at increased risk of disorders that do not follow Mendelian inheritance, but which are substantially more common in one sex than another (unequal sex incidence). Here, we examine the clinical and ethical issues to be considered prior to offering PGD gender selection to reduce the risk of a child being affected by a non-Mendelian condition with unequal sex incidence. , New uses of PGD have been reported in the past year for screening embryos for susceptibility to cancer, for late-onset diseases, for HLA-matching for existing children, and for gender. , This article describes current and likely future uses of PGD, and then analyses the ethical issues posed by new uses of PGD to screen embryos for susceptibility and late-onset conditions, for HLA-matching for tissue donation to an existing child, and for gender selection., The use of PGD for sex selection arouses considerable debate, especially in countries like India that have a marked cultural preference for boys. It is argued that using PGD for sex selection is a treatment option that can be ethically offered to couples who desire to use this technology to plan their families., Another concern is the use of this technology for nongenetic disorders such as gender selection. [SEP]Relations: chromosome separation has relations: bioprocess_protein with SMARCAD1, bioprocess_protein with SMARCAD1, bioprocess_protein with RECQL5, bioprocess_protein with RECQL5. Prostaglandin D2 has relations: drug_protein with PTGDR2, drug_protein with PTGDR2, drug_drug with Magnesium salicylate, drug_drug with Magnesium salicylate, drug_drug with Pirprofen, drug_drug with Pirprofen. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. PGD defined as following: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects.. mitochondrial disorders defined as following: Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.. chromosomal abnormalities defined as following: Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS..", "label": "yes"} {"id": "converted_1414", "sentence1": "Are genes symmetrically distributed between leading and lagging DNA strand in bacteria?", "sentence2": "Genomic DNA is used as the template for both replication and transcription, whose machineries may collide and result in mutagenesis, among other damages. Because head-on collisions are more deleterious than codirectional collisions, genes should be preferentially encoded on the leading strand to avoid head-on collisions, as is observed in most bacterial genomes examined., Most genes in bacteria are encoded on the leading strand of replication. This presumably avoids the potentially detrimental head-on collisions that occur between the replication and transcription machineries when genes are encoded on the lagging strand., The majority of bacterial genes are located on the leading strand, genes of some functional categories such as ribosome have higher preferences to be on the leading strands, genes of some functional categories such as transcription factor have higher preferences on the lagging strands, essential genes are more preferentially situated at the leading strand than at the lagging strand, remarkable strand-bias of the distribution of essential genes, Head-on encounters between the replication and transcription machineries on the lagging DNA strand can lead to replication fork arrest and genomic instability. To avoid head-on encounters, most genes, especially essential and highly transcribed genes, are encoded on the leading strand such that transcription and replication are co-directional., Replication-associated purine asymmetry may contribute to strand-biased gene distribution., strand-biased gene distribution (SGD), SGD correlates not only with polC, but also with purine asymmetry (PAS), In bacteria, most genes are on the leading strand of replication, a phenomenon attributed to collisions between the DNA and RNA polymerases., genes whose expression is important for fitness are selected to the leading strand because this reduces the duration of these interruptions, Among prokaryotic genomes, the distribution of genes on the leading and lagging strands of the replication fork is known to be biased. , We show that the evidence they provided is invalid and that the existence of lagging strand encoded genes is explainable by a balance between deleterious mutations that bring genes from the leading to the lagging strand and purifying selection purging such mutants., Based on those experimentally determined for 10 bacteria, we find that essential genes are more preferentially situated at the leading strand than at the lagging strand, for all the 10 genomes studied, confirming previous findings based on either smaller datasets or putatively assigned ones by homology search., The majority of bacterial genes are located on the leading strand, and the percentage of such genes has a large variation across different bacteria., Most genes in bacteria are encoded on the leading strand of replication., This paradox could be explained by assuming that the stronger mutation pressure and selection after inversion preferentially eliminate genes transferred from the leading to the lagging DNA strand., We have shown that the relative number of translocations which have switched positions of genes from the leading to the lagging DNA strand is lower than the number of translocations which have transferred genes from the lagging strand to the leading strand of prokaryotic genomes., Most genes in bacteria are encoded on the leading strand of replication, The majority of bacterial genes are located on the leading strand, and the percentage of such genes has a large variation across different bacteria, We have shown that the relative number of translocations which have switched positions of genes from the leading to the lagging DNA strand is lower than the number of translocations which have transferred genes from the lagging strand to the leading strand of prokaryotic genomes, Using Monte Carlo methods, we have simulated, under experimentally determined directional mutation pressure, the divergence rate and the elimination rate of genes depending on their location in respect to the leading/lagging DNA strands in the asymmetric prokaryotic genome[SEP]Relations: transcription factor binding has relations: molfunc_protein with CD34, molfunc_protein with CD34, molfunc_protein with TWIST1, molfunc_protein with TWIST1, molfunc_protein with SMARCA1, molfunc_protein with SMARCA1, molfunc_protein with MAFB, molfunc_protein with MAFB. Bacteremia has relations: disease_phenotype_positive with staphylococcal pneumonia, disease_phenotype_positive with staphylococcal pneumonia. Definitions: bacterial genomes defined as following: The genetic complement of a BACTERIA as represented in its DNA.. strand defined as following: The orientation of a genomic element on the double stranded molecule.. transcription factor defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. mutagenesis defined as following: Production of genetic alterations by any technique, including chemicals, radiation, recombination, or other molecular biology methods.. bacterial genes defined as following: The functional hereditary units of BACTERIA.. PAS defined as following: A 26-item, retrospective questionnaire designed to assess the degree of an individual's achievement of developmental goals from childhood through adulthood, prior to the onset of schizophrenia. This rating scale includes measures for sociability and social withdrawal, peer relationships, scholastic performance, adaptation to school, and ability to form socio-sexual relationships. Performance is scored on a 7-point scale ranging from 0 (healthiest adjustment) to 6 (lowest adjustment).. Genomic DNA defined as following: The DNA that is part of the normal chromosomal complement of an organism.. essential genes defined as following: Those genes found in an organism which are necessary for its viability and normal function.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. ribosome defined as following: Multicomponent ribonucleoprotein structures found in the CYTOPLASM of all cells, and in MITOCHONDRIA, and PLASTIDS. They function in PROTEIN BIOSYNTHESIS via GENETIC TRANSLATION.. translocations defined as following: Any type of genetic recombination involving exchange of DNA between non-homologous chromosomes, which often occurs as the result of non-homologous end-joining of broken DNA strands. Chromosomal translocation is involved in repairing broken DNA and in maintaining cell viability at the expense of long term genomic stability. This process is is associated with particular types of leukemia, infertility and Down Syndrome.. bacteria defined as following: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive..", "label": "no"} {"id": "converted_79", "sentence1": "Are there any urine biomarkers for chronic kidney disease?", "sentence2": "Kidney and urine proteomic biomarkers are considered as promising diagnostic tools to predict CKD progression early in diabetic nephropathy, facilitating timely and selective intervention that may reduce the related health-care expenditures., Both blood and urine biomarkers are reviewed in this paper and offer a considerable opportunity to enhance the understanding of the pathophysiology and known epidemiology of these recently defined syndromes., Cardiorenal syndromes (CRS) have been subclassified as five defined entities which represent clinical circumstances in which both the heart and the kidney are involved in a bidirectional injury and dysfunction via a final common pathway of cell-to-cell death and accelerated apoptosis mediated by oxidative stress., There is a strong association between both acute and chronic dysfunction of the heart and kidneys with respect to morbidity and mortality., Both blood and urine biomarkers, including the assessment of catalytic iron, a critical element to the generation of oxygen-free radicals and oxidative stress, are reviewed in this paper., Identification of urine biomarkers has proven to be beneficial in recent years because of ease of handling, stability, and the ability to standardize the various markers to creatinine or other peptides generally already present in the urine. Recent markers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and podocin have garnered a lot of attention. The emergence of these and other biomarkers is largely because of the evolution of novel genomic and proteomic applications in investigations of acute kidney injury and chronic kidney disease.[SEP]Relations: diabetic nephropathy has relations: disease_disease with chronic kidney disease, disease_disease with chronic kidney disease. Chronic kidney disease has relations: phenotype_phenotype with Stage 1 chronic kidney disease, phenotype_phenotype with Stage 1 chronic kidney disease, phenotype_phenotype with Stage 2 chronic kidney disease, phenotype_phenotype with Stage 2 chronic kidney disease, phenotype_phenotype with Renal insufficiency, phenotype_phenotype with Renal insufficiency, disease_phenotype_positive with nephrotic syndrome,, disease_phenotype_positive with nephrotic syndrome,. Definitions: CKD defined as following: Impairment of the renal function secondary to chronic kidney damage persisting for three or more months.. peptides defined as following: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.. NGAL defined as following: Human LCN2 wild-type allele is located in the vicinity of 9q34 and is approximately 5 kb in length. This allele, which encodes neutrophil gelatinase-associated lipocalin protein, may be involved in both the modulation of inflammation and the regulation of the transport of hydrophobic substances (ie. retinol, lipopolysaccharide). The expression of this gene may be elevated in many cancers and inflammatory diseases.. CRS defined as following: Transplacental infection of the fetus with rubella usually in the first trimester of pregnancy, as a consequence of maternal infection, resulting in various developmental abnormalities in the newborn infant. They include cardiac and ocular lesions, deafness, microcephaly, mental retardation, and generalized growth retardation. (From Dorland, 27th ed). genomic defined as following: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.. acute kidney injury defined as following: Sudden and sustained deterioration of the kidney function characterized by decreased glomerular filtration rate, increased serum creatinine or oliguria.. diabetic nephropathy defined as following: KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.. chronic kidney disease defined as following: Impairment of the renal function secondary to chronic kidney damage persisting for three or more months..", "label": "yes"} {"id": "converted_4497", "sentence1": "Should istiratumab be used for Pancreatic Cancer?", "sentence2": "CONCLUSIONS: Istiratumab failed to improve the efficacy of SOC chemotherapy in this patient setting. , In the high IGF-1 cohort, median PFS was 3.6 and 7.3 months in the experimental versus control arms, respectively [hazard ratio (HR) = 1.88, P = 0.027]. In the high IGF-1/HRG+ subgroup (n = 44), median PFS was 4.1 and 7.3 months, respectively (HR = 1.39, P = 0.42).[SEP]Relations: insulin-like growth factor I binding has relations: molfunc_protein with ITGAV, molfunc_protein with ITGAV, molfunc_protein with ITGA6, molfunc_protein with ITGA6, molfunc_protein with ITGB3, molfunc_protein with ITGB3, molfunc_protein with INSR, molfunc_protein with INSR, molfunc_protein with ITGB4, molfunc_protein with ITGB4. Definitions: IGF-1 defined as following: A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.. Pancreatic Cancer defined as following: A primary or metastatic malignant tumor involving the pancreas. Representative examples include carcinoma and lymphoma..", "label": "no"} {"id": "converted_1215", "sentence1": "Is zolpidem an antibiotic?", "sentence2": "Zolpidem is a short-acting imidazopyridine hypnotic drug that is metabolized mainly by CYP3A4., FGIN-1-27 and alpidem, like the neurosteroid 3 alpha,21-dehydroxy-5 alpha-pregnane-20-one (THDOC), clonazepam and zolpidem (the direct allosteric modulators of gamma-aminobutyric acidA receptors) delay the onset of isoniazid and metrazol-induced convulsions., olpidem is a new, short-acting hypnotic of imidazopyridine structure which binds selectively to a subpopulation of receptors involved in the action of benzodiazepines [omega 1 (BZ1) sites of the gamma-aminobutyric acidA receptors], lpidem is a new, short-acting hypnotic of imidazopyridine structure which binds selectively to a subpopulation of receptors involved in the action of benzodiazepines [omega 1 (BZ1) sites of the gamma-aminobutyric acidA receptors], In contrast, after repeated treatment with zolpidem, there was no change in its ability to produce sedative and anticonvulsant effects., Zolpidem, a novel nonbenzodiazepine hypnotic. I. Neuropharmacological and behavioral effects., Zolpidem [N,N,6-trimethyl-2-(4-methylphenyl)imidazo[1,2-a]pyridine-3-acetamide hemitartrate] is reported to be a rapid onset, short duration hypnotic that interacts at the benzodiazepine recognition site., The imidazopyridine zolpidem is a short-acting hypnotic chemically distinct from benzodiazepines (BZs)., According to its peculiar neuropharmacologic activity (selectivity for the omega 1-BZ receptors), zolpidem is expected to be a pure hypnotic, without the other effects of BZs.[SEP]Relations: Zolpidem has relations: drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Diacerein, drug_drug with Diacerein, drug_drug with Zotepine, drug_drug with Zotepine, drug_drug with Vitamin E, drug_drug with Vitamin E, drug_drug with Medazepam, drug_drug with Medazepam. Definitions: CYP3A4 defined as following: Catalysis of the reactions: taurochenodeoxycholate + NADPH + H+ + O2 = taurohyocholate + NADP+ + H2O, and lithocholate + NADPH + H+ + O2 = hyodeoxycholate + NADP+ + H2O. [RHEA:23644]. gamma-aminobutyric acidA receptors defined as following: Cell-surface proteins that bind GAMMA-AMINOBUTYRIC ACID with high affinity and trigger changes that influence the behavior of cells. GABA-A receptors control chloride channels formed by the receptor complex itself. They are blocked by bicuculline and usually have modulatory sites sensitive to benzodiazepines and barbiturates. GABA-B receptors act through G-proteins on several effector systems, are insensitive to bicuculline, and have a high affinity for L-baclofen.. zolpidem defined as following: An imidazopyridine derivative and short-acting GABA-A receptor agonist that is used for the treatment of INSOMNIA.. BZs defined as following: A hereditary disease characterized by multiple ectodermal, mesodermal, and endodermal nevoid and neoplastic anomalies. Facial trichilemmomas and papillomatous papules of the oral mucosa are the most characteristic lesions. Individuals with this syndrome have a high risk of BREAST CANCER; THYROID CANCER; and ENDOMETRIAL CANCER. This syndrome is associated with mutations in the gene for PTEN PHOSPHATASE.. benzodiazepines defined as following: A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.. clonazepam defined as following: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of GAMMA-AMINOBUTYRIC ACID receptor responses.. isoniazid defined as following: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis..", "label": "no"} {"id": "converted_4540", "sentence1": "Do only changes in coding regions of MEF2C cause developmental disorders?", "sentence2": "Non-coding region variants upstream of MEF2C cause severe developmental disorder through three distinct loss-of-function mechanisms., Clinical genetic testing of protein-coding regions identifies a likely causative variant in only around half of developmental disorder (DD) cases. The contribution of regulatory variation in non-coding regions to rare disease, including DD, remains very poorly understood. We screened 9,858 probands from the Deciphering Developmental Disorders (DDD) study for de novo mutations in the 5' untranslated regions (5' UTRs) of genes within which variants have previously been shown to cause DD through a dominant haploinsufficient mechanism. We identified four single-nucleotide variants and two copy-number variants upstream of MEF2C in a total of ten individual probands. We developed multiple bespoke and orthogonal experimental approaches to demonstrate that these variants cause DD through three distinct loss-of-function mechanisms, disrupting transcription, translation, and/or protein function. These non-coding region variants represent 23% of likely diagnoses identified in MEF2C in the DDD cohort, but these would all be missed in standard clinical genetics approaches. Nonetheless, these variants are readily detectable in exome sequence data, with 30.7% of 5' UTR bases across all genes well covered in the DDD dataset. Our analyses show that non-coding variants upstream of genes within which coding variants are known to cause DD are an important cause of severe disease and demonstrate that analyzing 5' UTRs can increase diagnostic yield. We also show how non-coding variants can help inform both the disease-causing mechanism underlying protein-coding variants and dosage tolerance of the gene.[SEP]Relations: developmental disability has relations: disease_protein with MECP2, disease_protein with MECP2. MEF2C has relations: disease_protein with intellectual disability, disease_protein with intellectual disability, disease_protein with autism spectrum disorder, disease_protein with autism spectrum disorder, disease_protein with autism (disease), disease_protein with autism (disease), disease_protein with autism susceptibility 1, disease_protein with autism susceptibility 1. Definitions: variants defined as following: An alteration or difference from a norm or standard.. gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. MEF2C defined as following: This gene plays a role in muscular and vascular development.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. developmental disorder defined as following: Disorders in which there is a delay in development based on that expected for a given age level or stage of development. These impairments or disabilities originate before age 18, may be expected to continue indefinitely, and constitute a substantial impairment. Biological and nonbiological factors are involved in these disorders. (From American Psychiatric Glossary, 6th ed).", "label": "no"} {"id": "converted_3984", "sentence1": "Should minocycline be used for mild Alzheimer disease?", "sentence2": "Conclusions and Relevance: Minocycline did not delay the progress of cognitive or functional impairment in people with mild AD during a 2-year period. [SEP]Relations: Minocycline has relations: drug_effect with Arthritis, drug_effect with Arthritis, contraindication with kidney disease, contraindication with kidney disease, contraindication with liver disease, contraindication with liver disease, contraindication with gallbladder disease, contraindication with gallbladder disease, drug_effect with Dyssynergia, drug_effect with Dyssynergia. Definitions: Minocycline defined as following: A TETRACYCLINE analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant STAPHYLOCOCCUS infections.. minocycline defined as following: A TETRACYCLINE analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant STAPHYLOCOCCUS infections..", "label": "no"} {"id": "converted_1298", "sentence1": "Are there Conserved Noncoding Elements (CNEs) in invertebrate genomes?", "sentence2": "Here, we use genome-wide comparisons between C. intestinalis and C. savignyi to identify putative urochordate cis-regulatory sequences. Ciona conserved non-coding elements (ciCNEs) are associated with largely the same key regulatory genes as vertebrate CNEs, We have identified Conserved Non-coding Elements (CNEs) in the regulatory region of Caenorhabditis elegans and Caenorhabditis briggsae , Here we report that nematode genomes contain an alternative set of CNEs that share sequence characteristics, but not identity, with their vertebrate counterparts. CNEs thus represent a very unusual class of sequences that are extremely conserved within specific animal lineages yet are highly divergent between lineages, A core set of genes that regulate development is associated with CNEs across three animal groups (worms, flies and vertebrates), The genomes of vertebrates, flies, and nematodes contain highly conserved noncoding elements (CNEs)., The genomes of vertebrates, flies, and nematodes contain highly conserved noncoding elements (CNEs)[SEP]Relations: vertebra has relations: anatomy_anatomy with non-transverse process-bearing vertebra, anatomy_anatomy with non-transverse process-bearing vertebra, anatomy_anatomy with vertebral element, anatomy_anatomy with vertebral element, anatomy_anatomy with transverse process-bearing vertebra, anatomy_anatomy with transverse process-bearing vertebra. regulation of RNA polymerase I regulatory region sequence-specific DNA binding has relations: bioprocess_bioprocess with regulation of transcription regulatory region DNA binding, bioprocess_bioprocess with regulation of transcription regulatory region DNA binding, bioprocess_bioprocess with negative regulation of RNA polymerase I regulatory region sequence-specific DNA binding, bioprocess_bioprocess with negative regulation of RNA polymerase I regulatory region sequence-specific DNA binding. Definitions: regulatory genes defined as following: Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.. sequences defined as following: The sequence of nucleotide residues along a DNA chain.. regulatory region defined as following: Nucleic acid sequences involved in regulating the expression of genes.. genomes defined as following: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.. vertebrates defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes.. nematodes defined as following: class of unsegmented helminths with fundamental bilateral symmetry and secondary triradiate symmetry of the oral and esophageal structures; many species are parasites.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. flies defined as following: An order of the class Insecta. Wings, when present, number two and distinguish Diptera from other so-called flies, while the halteres, or reduced hindwings, separate Diptera from other insects with one pair of wings. The order includes the families Calliphoridae, Oestridae, Phoridae, SARCOPHAGIDAE, Scatophagidae, Sciaridae, SIMULIIDAE, Tabanidae, Therevidae, Trypetidae, CERATOPOGONIDAE; CHIRONOMIDAE; CULICIDAE; DROSOPHILIDAE; GLOSSINIDAE; MUSCIDAE; TEPHRITIDAE; and PSYCHODIDAE. The larval form of Diptera species are called maggots (see LARVA)..", "label": "yes"} {"id": "converted_516", "sentence1": "Is there an association between TERT promoter mutation and survival of glioma patients?", "sentence2": "Mutations lead to TERT upregulation and are associated with aggressive clinical behavior in glioblastomas., Kaplan-Meier's survival analysis showed that TERT promoter mutation (P=0.037), Isocitrate dehydrogenase (IDH) mutation (P<0.001), and 1p/19q codeletion (P<0.001) were associated with favorable overall survival (OS). In the subset of 116 IDH-mutated lower-grade gliomas lacking 1p/19q codeletion, 19 TERT promoter-mutated tumors exhibited longer progression-free survival (PFS) (P=0.027) and OS (P=0.004). Consistent with this observation, in the subset of 97 IDH-mutated astrocytomas, 14 TERT promoter-mutated tumors showed longer PFS (P=0.001) and OS (P=0.001). In contrast, among the subset of 74 IDH wild-type lower-grade gliomas with intact 1p/19q, TERT promoter mutation was associated with shorter PFS (P=0.001) and OS (P=0.001). Similarly, in the subset of 65 IDH wild-type astrocytomas, 16 TERT promoter-mutated tumors exhibited unfavorable PFS (P=0.007) and OS (P=0.008). Our results indicate that when combined with IDH status, TERT promoter mutation contributes to prognostic subgroups of lower-grade astrocytic tumors or 1p/19q intact lower-grade gliomas and this may further refine future molecular classification of lower-grade gliomas., RESULTS: TERTp-mut identified in 60.8% of gliomas (491 out of 807) was globally associated with poorer outcome (Hazard ratio (HR)=1.50). , TERT promoter mutations lead to high transcriptional activity under hypoxia and temozolomide treatment and predict poor prognosis in gliomas., Patients with TERT promoter mutations had lower survival rates, even after adjusting for other known or potential risk factors, and the incidence of mutation was correlated with patient age., TERT promoter mutations maintained its ability of inducing high transcriptional activity even under hypoxic and TMZ treatment conditions, and the presence of mutations was associated with poor prognosis in glioma patients. , Patients whose Grade III-IV gliomas exhibit TERT promoter mutations alone predominately have primary GBMs associated with poor median OS (11.5 months). Patients whose Grade III-IV gliomas exhibit IDH1/2 mutations alone predominately have astrocytic morphologies and exhibit a median OS of 57 months while patients whose tumors exhibit both TERT promoter and IDH1/2 mutations predominately exhibit oligodendroglial morphologies and exhibit median OS of 125 months., Patients with TERT promoter mutations had lower survival rates, even after adjusting for other known or potential risk factors, and the incidence of mutation was correlated with patient age.CONCLUSION: TERT promoter mutations were specific to gliomas. , We defined, based on TERTp-mut and IDH mutation status, four prognostic groups: (1) TERTp-mut and IDH-mut associated with 1p19q codeletion, overall survival (OS)>17 years; (2) TERTp-wt and IDH-mut, associated with TP53 mutation, OS=97.5 months; (3) TERTp-wt and IDH-wt, with no specific association, OS=31.6 months; (4) TERTp-mut and IDH-wt, associated with EGFR amplification, OS=15.4 months. , Mutations lead to TERT upregulation and are associated with aggressive clinical behavior in glioblastomas. , In the subset of 116 IDH-mutated lower-grade gliomas lacking 1p/19q codeletion, 19 TERT promoter-mutated tumors exhibited longer progression-free survival (PFS) (P=0.027) and OS (P=0.004). , The mean age at diagnosis was lowest (37 years) among patients who had gliomas with only IDH mutations and was highest (59 years) among patients who had gliomas with only TERT mutations. The molecular groups were independently associated with overall survival among patients with grade II or III gliomas but not among patients with grade IV gliomas., Mutations were detected in gliomas, but not in meningiomas, pituitary adenomas, cavernomas, intracranial metastases, normal brain tissues, or peripheral blood of glioma patients. Patients with TERT promoter mutations had lower survival rates, even after adjusting for other known or potential risk factors, and the incidence of mutation was correlated with patient age.[SEP]Relations: Glioma has relations: disease_phenotype_positive with glioma susceptibility, disease_phenotype_positive with glioma susceptibility, disease_phenotype_positive with glioblastoma (disease), disease_phenotype_positive with glioblastoma (disease), disease_phenotype_positive with retinoblastoma, disease_phenotype_positive with retinoblastoma, drug_effect with Aminolevulinic acid, drug_effect with Aminolevulinic acid, disease_phenotype_positive with Turcot syndrome with polyposis, disease_phenotype_positive with Turcot syndrome with polyposis. Definitions: Isocitrate dehydrogenase defined as following: An enzyme of the oxidoreductase class that catalyzes the conversion of isocitrate and NAD+ to yield 2-ketoglutarate, carbon dioxide, and NADH. It occurs in cell mitochondria. The enzyme requires Mg2+, Mn2+; it is activated by ADP, citrate, and Ca2+, and inhibited by NADH, NADPH, and ATP. The reaction is the key rate-limiting step of the citric acid (tricarboxylic) cycle. (From Dorland, 27th ed) (The NADP+ enzyme is EC 1.1.1.42.) EC 1.1.1.41.. meningiomas defined as following: A relatively common neoplasm of the CENTRAL NERVOUS SYSTEM that arises from arachnoidal cells. The majority are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Meningiomas have a predilection to arise from the parasagittal region, cerebral convexity, sphenoidal ridge, olfactory groove, and SPINAL CANAL. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2056-7). TP53 defined as following: Human TP53 wild-type allele is located in the vicinity of 17p13.1 and is approximately 19 kb in length. This allele, which encodes cellular tumor antigen p53 protein, plays a role in cell cycle regulation during the G0/G1transition. Alterations of the TP53 gene occur as both somatic and germline mutations in human malignancies in select cancer-prone families with Li-Fraumeni syndrome.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. TERT defined as following: Human TERT wild-type allele is located in the vicinity of 5p15.33 and is approximately 42 kb in length. This allele, which encodes telomerase reverse transcriptase protein, is involved in the replication of telomeres. Aberrant expression of the allele at elevated levels may contribute to oncogenesis.. pituitary adenomas defined as following: A non-metastasizing tumor that arises from the adenohypophysial cells of the anterior lobe of the pituitary gland. The tumor can be hormonally functioning or not. The diagnosis can be based on imaging studies and/or radioimmunoassays. Due to its location in the sella turcica, expansion of the tumor mass can impinge on the optic chiasm or involve the temporal lobe, third ventricle and posterior fossa A frequently associated physical finding is bitemporal hemianopsia which may progress to further visual loss.. gliomas defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21). TMZ defined as following: A dacarbazine derivative that is used as an alkylating antineoplastic agent for the treatment of MALIGNANT GLIOMA and MALIGNANT MELANOMA.. glioblastomas defined as following: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. hypoxia defined as following: A disorder characterized by a decrease in the level of oxygen in the body.. IDH defined as following: Infective dermatitis associated with HTLV-1 is a rare and severe chronic disease characterized by recurrent chronic eczema (with erythematous, scaly and crusted lesions) mainly affecting seborrheic areas (e.g. scalp, forehead, eyelids, paranasal and periauricular skin, neck, axillae, and groin), a generalized fine papular rash, chronic nasal discharge with crusting of the anterior nares, and non-virulent <i>Staphylococcus aureus</i> or beta-hemolytic <i>Streptococcus</i> infections, thought to be a result of HTLV-1-induced immunosuppression. Lymphadenopathy, anemia, mild to moderate pruritus and increased incidence of other infections (e.g. crusted scabies) have also been reported in some patients. Patients may subsequently develop other HTLV-1 associated conditions such as adult T-cell leukemia/lymphoma and tropical spastic paraparesis (see these terms).. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"} {"id": "converted_1739", "sentence1": "Is there a relationship between thyroid hormone altered metabolism and coronary artery disease?", "sentence2": "The results showed that higher levels of TSH within the reference range were independently associated with the presence of CAD only among subjects less than or equal to 65 years old, suggesting age might influence the relationship., FT3 levels within the normal range were inversely correlated with the presence and severity of CAD. Moreover, lower FT3 concentrations were correlated with the Gensini score and independently predicted the presence and severity of CAD., High TSH within the reference range was associated with increased risk of coronary death in women (P(trend) 0·005), but not in men. The risk of coronary death was also increased among women with subclinical hypothyroidism or subclinical hyperthyroidism, compared to women with TSH of 0·50-1·4 mU/l. , Prevalence of CHD was more common in hypothyroid and moderate SCH patients., The angiographic results were as follows: significant coronary disease (SH 28.1% vs. non-SH 43.8%; p=0.087); three-vessel disease (9.4% vs. 9.9%; p=0.919); two-vessel disease (12.5% vs. 13.4%; p=0.892); single-vessel disease (6.3% vs. 29.5%; p=0.051); minimal lesions (9.4% vs. 10.9%; p=0.794); and no coronary disease (62.4% vs, 45.3%; p=0.064)., Lower fT3 levels were predictive of both single-vessel (p = 0.012) and multivessel (p = 0.009) CAD. Through a multivariate logistic regression analysis, fT3 was still linked to the presence of CAD (hazard ratio [HR]: 0.48, 95% confidence interval [CI]: 0.34-0.68, p < 0.001)., Our study showed that FT(4) levels were associated with the presence and the severity of CAD. Also, this study suggests that elevated serum FT(4) levels even within normal range could be a risk factor for CAD. , The present meta-analysis indicates that sub-clinical hypothyroidism is associated with both, a significant risk of CHD at baseline and at follow-up., The incidence of multi-vessel disease was higher in patients with high TSH level (p=0.026). TSH level showed a significant correlation with age (r=0.109, p=0.044) and Gensini's score (r=0.117, p=0.045). The multivariate analysis revealed that age (OR 2.39, p=0.001), diabetes (OR 3.74, p=0.001), creatinine (OR 2.06, p=0.008), and smoking (OR 1.85, p=0.045) were independent predictors for significant coronary artery disease, but TSH level did not predict coronary artery stenosis., These data in patients referred for coronary angiography suggest that variation of thyroid function within the statistical normal range may influence the presence and severity of coronary atherosclerosis.[SEP]Relations: coronary artery disease has relations: disease_disease with arterial disorder, disease_disease with arterial disorder, disease_disease with heart disease, disease_disease with heart disease, disease_disease with coronary heart disease, susceptibility to, disease_disease with coronary heart disease, susceptibility to, disease_disease with congenital coronary artery anomaly, disease_disease with congenital coronary artery anomaly, disease_disease with intermediate coronary syndrome, disease_disease with intermediate coronary syndrome. Definitions: FT3 defined as following: A traditional unit of volume equal to 1728 cubic inches, or 1/27 cubic yard, or 0.028 316 85 cubic meter (28.316 85 liters). The cubic foot holds about 7.4805 US gallons.. coronary artery stenosis defined as following: Narrowing or constriction of a coronary artery.. coronary artery disease defined as following: Thickening and loss of elasticity of the CORONARY ARTERIES, leading to progressive arterial insufficiency (CORONARY DISEASE).. hypothyroid defined as following: A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction.. diabetes defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.. coronary disease defined as following: Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause.. SCH defined as following: A hysterectomy that removes the uterus and leaves the cervix in place.. thyroid hormone defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs..", "label": "yes"} {"id": "converted_2501", "sentence1": "Down's syndrome occurs when an individual has an extra copy or part of a copy of chromosome 21, yes or no?", "sentence2": "Down syndrome (DS; trisomy 21) is the most common survivable disorder due to aneuploidy., Down syndrome (DS), trisomy 21, is caused by increased dose of genes present on human chromosome 21 (HSA21), Down syndrome, or Trisomy 21, is the most frequently occurring chromosomal abnormality in live-born children. , Down syndrome (DS), caused by trisomy of chromosome 21,, Submicroscopic duplication of chromosome 21 and trisomy 21 phenotype (Down syndrome)., Trisomy 21 or Down syndrome is a chromosomal disorder resulting from the presence of all or part of an extra Chromosome 21., Down syndrome is a genetic disorder, occurring when an individual has all or part of an extra copy of chromosome 21., Downs syndrome (DS) occurs due to an extra copy of chromosome 21., Down syndrome, which arises in individuals carrying an extra copy of chromosome 21, is associated with a greatly increased risk of early-onset Alzheimer disease., Aneuploidy refers to the presence of an extra copy of a specific chromosome, or trisomy, as seen in Down's syndrome (trisomy 21), or the absence of a single chromosome, or monosomy, as seen in Turner syndrome (a single X chromosome in females: 45, X)., Down syndrome (DS) or Trisomy 21 (Ts21) is caused by the presence of an extra copy of all or part of human chromosome 21 (Hsa21) and is the most frequent survivable congenital chromosomal abnormality., Down syndrome (DS) is a major cause of mental retardation and heart disease. Although it is usually caused by the presence of an extra chromosome 21, a subset of the diagnostic features may be caused by the presence of only band 21q22., Down syndrome is usually caused by complete trisomy 21., Down syndrome, the most frequent genetic disorder, is characterized by an extra copy of all or part of chromosome 21., Down syndrome (DS), caused by an extra copy of chromosome 21, affects 1 in 750 live births and is characterized by cognitive impairment and a constellation of congenital defects., Down syndrome (DS) results from one extra copy of human chromosome 21 and leads to several alterations including intellectual disabilities and locomotor defects., Down's syndrome results from the production of three copies of chromosome 21 within a cell. , Downs syndrome (DS) occurs due to an extra copy of chromosome 21., Trisomy 21 (Ts21) is the most common live-born human aneuploidy; it results in a constellation of features known as Down's syndrome (DS)., Down syndrome comprises multiple malformations and is due to trisomy of chromosome 21., n 1959, J. Lejeune, M. Gautier, and R. Turpin demonstrated that the children with Down syndrome had an extra copy of chromosome 21., To develop a reliable and specific method for rapid prenatal diagnosis of Trisomy 21 (Down syndrome)., Trisomy 21 Down syndrome is the most common genetic cause for congenital malformations and intellectual disability, Down syndrome, characterized by an extra chromosome 21 is the most common genetic cause for congenital malformations and learning disability. [SEP]Relations: Down syndrome has relations: disease_protein with S100B, disease_protein with S100B, disease_phenotype_positive with Sporadic, disease_phenotype_positive with Sporadic, disease_protein with RAD21, disease_protein with RAD21, disease_phenotype_positive with Abnormality of the lymphatic system, disease_phenotype_positive with Abnormality of the lymphatic system, disease_protein with NRAS, disease_protein with NRAS. Definitions: chromosome 21 defined as following: A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.. learning disability defined as following: Conditions characterized by a significant discrepancy between an individual's perceived level of intellect and their ability to acquire new language and other cognitive skills. These may result from organic or psychological conditions. Relatively common subtypes include DYSLEXIA, DYSCALCULIA, and DYSGRAPHIA.. human defined as following: Members of the species Homo sapiens.. intellectual disability defined as following: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28). Downs syndrome defined as following: A chromosome disorder associated either with an extra CHROMOSOME 21 or an effective TRISOMY for chromosome 21. Clinical manifestations include HYPOTONIA, short stature, BRACHYCEPHALY, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, single transverse palmar crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213). chromosomal disorder defined as following: Clinical conditions caused by an abnormal chromosome constitution in which there is extra or missing chromosome material (either a whole chromosome or a chromosome segment). (from Thompson et al., Genetics in Medicine, 5th ed, p429). heart disease defined as following: Pathological conditions involving the HEART including its structural and functional abnormalities.. congenital defects defined as following: Malformations of organs or body parts during development in utero.. Turner syndrome defined as following: A syndrome of defective gonadal development in phenotypic females associated with the karyotype 45,X (or 45,XO). Patients generally are of short stature with undifferentiated GONADS (streak gonads), SEXUAL INFANTILISM, HYPOGONADISM, webbing of the neck, cubitus valgus, elevated GONADOTROPINS, decreased ESTRADIOL level in blood, and CONGENITAL HEART DEFECTS. NOONAN SYNDROME (also called Pseudo-Turner Syndrome and Male Turner Syndrome) resembles this disorder; however, it occurs in males and females with a normal karyotype and is inherited as an autosomal dominant.. multiple malformations defined as following: Congenital abnormalities that affect more than one organ or body structure.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. Down's syndrome defined as following: A chromosome disorder associated either with an extra CHROMOSOME 21 or an effective TRISOMY for chromosome 21. Clinical manifestations include HYPOTONIA, short stature, BRACHYCEPHALY, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, single transverse palmar crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213).", "label": "yes"} {"id": "converted_4601", "sentence1": "Is Epistaxis associated with dental implant placement?", "sentence2": " The overall survival rate of the implants into the sinus cavity was 95.6%, without statistical differences according to the level of penetration. The clinical and radiological complications were 3.4% and 14.8% respectively. The most frequent clinical complication was the epistaxis, , implant placement and protrusion of the implant up to 3mm beyond the sinus floor does not alter the stability and outcome of dental implants, one year post-restoration. This could be associated with minor complications ranging from epistaxis to sinusitis, which are manageable.[SEP]Relations: Epistaxis has relations: drug_effect with Nicotine, drug_effect with Nicotine, drug_effect with Topotecan, drug_effect with Topotecan, drug_effect with Estradiol, drug_effect with Estradiol, drug_effect with Montelukast, drug_effect with Montelukast, drug_effect with Thiotepa, drug_effect with Thiotepa. Definitions: epistaxis defined as following: Bleeding from the nose.. sinusitis defined as following: Inflammation of the NASAL MUCOSA in one or more of the PARANASAL SINUSES.. Epistaxis defined as following: Bleeding from the nose..", "label": "yes"} {"id": "converted_4226", "sentence1": "Is phosphoenolpyruvate carboxykinase 1 (PCK1) the rate-limiting enzyme in gluconeogenesis?", "sentence2": "Phosphoenolpyruvate carboxykinase (PEPCK) is a metabolic enzyme in the gluconeogenesis pathway,, PEPCK, a key enzyme involved in gluconeogenesis associated with a decrease in the expression of master genes involved in the VLDL synthesis , Transcriptome analysis of rate-limiting enzymes involved in hepatic gluconeogenesis revealed that moxifloxacin and gatifloxacin at a concentration of 1000 μM did not affect the expression of key gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase, glucose 6-phosphatase, and fructose 1,6-bisphosphatase., Pck1 is a rate-limiting gluconeogenic enzyme, where its deficiency or mutation contributes to serious clinical situations as neonatal hypoglycemia and liver failure., the gluconeogenesis key enzymes PEPCK (phosphoenolpyruvate carboxykinase) [SEP]Relations: phosphoenolpyruvate carboxykinase deficiency has relations: disease_protein with PCK1, disease_protein with PCK1, disease_protein with PCK2, disease_protein with PCK2, disease_disease with gluconeogenesis disorder, disease_disease with gluconeogenesis disorder. gluconeogenesis has relations: bioprocess_protein with PCK1, bioprocess_protein with PCK1, bioprocess_protein with PCK2, bioprocess_protein with PCK2. Definitions: phosphoenolpyruvate carboxykinase defined as following: An enzyme of the lyase class that catalyzes the conversion of ATP and oxaloacetate to ADP, phosphoenolpyruvate, and carbon dioxide. The enzyme is found in some bacteria, yeast, and Trypanosoma, and is important for the photosynthetic assimilation of carbon dioxide in some plants. EC 4.1.1.49.. gatifloxacin defined as following: A fluoroquinolone antibacterial agent and DNA TOPOISOMERASE II inhibitor that is used as an ophthalmic solution for the treatment of BACTERIAL CONJUNCTIVITIS.. gluconeogenesis defined as following: Biosynthesis of GLUCOSE from nonhexose or non-carbohydrate precursors, such as LACTATE; PYRUVATE; ALANINE; and GLYCEROL.. glucose 6-phosphatase defined as following: An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC 3.1.3.9.. hypoglycemia defined as following: A syndrome of abnormally low BLOOD GLUCOSE level. Clinical hypoglycemia has diverse etiologies. Severe hypoglycemia eventually lead to glucose deprivation of the CENTRAL NERVOUS SYSTEM resulting in HUNGER; SWEATING; PARESTHESIA; impaired mental function; SEIZURES; COMA; and even DEATH.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. PEPCK defined as following: An enzyme with high affinity for carbon dioxide. It catalyzes irreversibly the formation of oxaloacetate from phosphoenolpyruvate and carbon dioxide. This fixation of carbon dioxide in several bacteria and some plants is the first step in the biosynthesis of glucose. EC 4.1.1.31.. moxifloxacin defined as following: A fluoroquinolone antibiotic with antibacterial activity. Moxifloxacin binds to and inhibits the bacterial enzymes DNA gyrase (topoisomerase II) and topoisomerase IV, resulting in inhibition of DNA replication and repair and cell death in sensitive bacterial species.. fructose defined as following: A monosaccharide in sweet fruits and honey that is soluble in water, alcohol, or ether. It is used as a preservative and an intravenous infusion in parenteral feeding.. liver failure defined as following: Severe inability of the LIVER to perform its normal metabolic functions, as evidenced by severe JAUNDICE and abnormal serum levels of AMMONIA; BILIRUBIN; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; LACTATE DEHYDROGENASES; and albumin/globulin ratio. (Blakiston's Gould Medical Dictionary, 4th ed).", "label": "yes"} {"id": "converted_1995", "sentence1": "Are there canonical marks of active chromatin in developmentally regulated genes?", "sentence2": "Absence of canonical marks of active chromatin in developmentally regulated genes., The interplay of active and repressive histone modifications is assumed to have a key role in the regulation of gene expression. In contrast to this generally accepted view, we show that the transcription of genes temporally regulated during fly and worm development occurs in the absence of canonically active histone modifications. Conversely, strong chromatin marking is related to transcriptional and post-transcriptional stability, an association that we also observe in mammals. Our results support a model in which chromatin marking is associated with the stable production of RNA, whereas unmarked chromatin would permit rapid gene activation and deactivation during development. In the latter case, regulation by transcription factors would have a comparatively more important regulatory role than chromatin marks., Absence of canonical marks of active chromatin in developmentally regulated genes, Absence of canonical marks of active chromatin in developmentally regulated genes., In contrast to this generally accepted view, we show that the transcription of genes temporally regulated during fly and worm development occurs in the absence of canonically active histone modifications.[SEP]Relations: RNA localization to chromatin has relations: bioprocess_protein with HNRNPU, bioprocess_protein with HNRNPU. histone modification has relations: bioprocess_bioprocess with covalent chromatin modification, bioprocess_bioprocess with covalent chromatin modification. transcription factor binding has relations: molfunc_protein with METTL23, molfunc_protein with METTL23, molfunc_protein with PSMD10, molfunc_protein with PSMD10, molfunc_protein with ZNF618, molfunc_protein with ZNF618. Definitions: chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. histone modifications defined as following: The covalent alteration of one or more amino acid residues within a histone protein. [GOC:krc]. transcription factors defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. RNA defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. mammals defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young..", "label": "no"} {"id": "converted_1427", "sentence1": "Can cffDNA be used for non-invasive testing?", "sentence2": "Non-invasive prenatal testing using cell-free fetal DNA in maternal circulation, The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible., In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection.With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future. This review briefly summarizes the technical aspects of the NIPT and application of NIPT in clinical practice., First identified in 1997, cell-free fetal DNA (cffDNA) has just recently been used to detect fetal aneuploidy of chromosomes 13, 18, and 21, showing its potential to revolutionize prenatal genetic testing as a non-invasive screening tool, To determine how adults in the United States view non-invasive prenatal testing using cell-free fetal DNA (cffDNA testing) in order to help estimate uptake, Non-invasive prenatal testing of cell-free fetal DNA (cffDNA) in maternal plasma can predict the fetal RhD type in D negative pregnant women, The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible, The effectiveness and clinical utility of non-invasive prenatal diagnosis (NIPD) for fetal sex determination using cell-free fetal DNA (cffDNA) was assessed by undertaking a prospective national audit of UK testing, The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field, Non-invasive prenatal aneuploidy testing that utilizes cell-free fetal DNA (cffDNA) circulating in maternal blood is one example of an innovative technology that promises significant benefits for its intended end users; however, it is currently uncertain whether it will achieve widespread clinical implementation, Analysis of cell free fetal (cff) DNA in maternal plasma is used routinely for non invasive prenatal diagnosis (NIPD) of fetal sex determination, fetal rhesus D status and some single gene disorders, Non-invasive prenatal diagnosis (NIPD) using cell-free fetal DNA (cffDNA) in maternal plasma is an alternative to invasive prenatal diagnosis (IPD), which carries a 1% risk of miscarriage. , The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field. , The effectiveness and clinical utility of non-invasive prenatal diagnosis (NIPD) for fetal sex determination using cell-free fetal DNA (cffDNA) was assessed by undertaking a prospective national audit of UK testing. , NIFTY (Non-invasive Fetal Trisomy Test) is a non-invasive prenatal test which is used for diagnosing fetal trisomy. The test is based on the analysis of cell free fetal DNA (cffDNA) present in the plasma and serum of a pregnant woman., Using non-invasive method of cffDNAs in the shortest time possible, as well as avoiding invasive tests for early determination of fetal gender, provides the opportunity of deciding and employing early treatment for fetuses at risk of genetic diseases., The identification of cell-free fetal DNA (cffDNA) in maternal circulation has made non-invasive prenatal testing (NIPT) possible., To determine how adults in the United States view non-invasive prenatal testing using cell-free fetal DNA (cffDNA testing) in order to help estimate uptake., Nowadays, new advances in the use of cell free fetal DNA (cffDNA) in maternal plasma of pregnant women has provided the possibility of applying cffDNA in prenatal diagnosis as a non-invasive method., Non-invasive prenatal testing of cell-free fetal DNA (cffDNA) in maternal plasma can predict the fetal RhD type in D negative pregnant women., Prevention of contamination following our anti-contamination criteria is a good practice for certain non-invasive sex determination, using cffDNA.[SEP]Relations: infantile dystonia-parkinsonism has relations: disease_phenotype_positive with Ocular flutter, disease_phenotype_positive with Ocular flutter, disease_phenotype_positive with Absent speech, disease_phenotype_positive with Absent speech, disease_phenotype_positive with Autosomal recessive inheritance, disease_phenotype_positive with Autosomal recessive inheritance, disease_phenotype_positive with Rigidity, disease_phenotype_positive with Rigidity, disease_phenotype_positive with Incoordination, disease_phenotype_positive with Incoordination. Definitions: fetal defined as following: Care provided the pregnant woman in order to prevent complications, and decrease the incidence of maternal and prenatal mortality.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. IPD defined as following: An autosomal recessive condition caused by mutation(s) in the SLC6A3 gene, encoding sodium-dependent dopamine transporter. It is characterized by Parkinsonian features and has an onset in early infancy..", "label": "yes"} {"id": "converted_1817", "sentence1": "Is SUMOylation a post-translational modification in eukaryotes?", "sentence2": "SUMOylation, the conjugation of target proteins with SUMO (small ubiquitin-related modifier), is a type of post-translational modification in eukaryotes and involves the sequential action of activation (E1), conjugation (E2) and ligation (E3) enzymes. , Plants have evolved to cope with changing environmental conditions. One way plants achieve this is through post-translational modification of target proteins by ubiquitination and SUMOylation., Sumoylation is a post-translational modification essential in most eukaryotes that regulates stability, localization, activity, or interaction of a multitude of proteins., SUMOylation, the covalent attachment of a member of the small ubiquitin-like modifier (SUMO) family of proteins to lysines in target substrates, is an essential post-translational modification in eukaryotes. , Post-translational modification by SUMO is a highly conserved pathway in eukaryotes that plays very important regulatory roles in many cellular processes. , SUMOylation is an essential post-translational modification that regulates a variety of cellular processes including cell cycle progression. Although the SUMOylation pathway has been identified and investigated in many eukaryotes, the mechanisms of SUMOylation in regulating the functions of various substrates are still poorly understood. , SUMOylation is a relevant protein post-translational modification in eukaryotes., SUMOylation is a reversible post-translational modification essential for genome stability., Many SUMOylated lysines have previously been reported to be ubiquitinated, acetylated or methylated, thus indicating cross-talk between SUMO and other post-translational modifications., Sumoylation is a post-translational modification shown to play a role in diverse biological processes., Besides phosphorylation or ubiquitylation, for which many examples of modulation by pathogens exist, a post-translational modification called SUMOylation was recently shown to be targeted by pathogenic bacteria., cruzi SUMOylated proteins are similarly modified, indicating conserved functions for protein SUMOylation in this early divergent eukaryote., PML is a potent tumor suppressor and proapoptotic factor and is functionally regulated by post-translational modifications such as phosphorylation, sumoylation, and ubiquitination., SUMOylation is an essential post-translational modification that regulates a variety of cellular processes including cell cycle progression., SUMOylation in Giardia lamblia: A Conserved Post-Translational Modification in One of the Earliest Divergent Eukaryotes, SUMOylation, the covalent attachment of a member of the small ubiquitin-like modifier (SUMO) family of proteins to lysines in target substrates, is an essential post-translational modification in eukaryotes, SUMOylation is a relevant protein post-translational modification in eukaryotes, Post-translational modifications (PTMs) are one facet of this proteasomal regulation, with over 400 known phosphorylation sites, over 500 ubiquitination sites and 83 internal lysine acetylation sites, as well as multiple sites for caspase cleavage, glycosylation (such as O-GlcNAc modification), methylation, nitrosylation, oxidation, and SUMOylation, SUMOylation is an important post-translational modification, and Akt SUMOylation was found to regulate cell proliferation, tumorigenesis and cell cycle, but the molecular mechanism of Akt SUMOylation is less well known, SUMOylation is a form of post-translational modification where small ubiquitin-like modifiers (SUMO) are covalently attached to target proteins to regulate their properties, One distinctive feature in acute proteotoxic stresses, such as heat shock (HS), is rapid post-translational modification of proteins by SUMOs (small ubiquitin-like modifier proteins; SUMOylation), Post-translational modification by the Small Ubiquitin-like Modifier (SUMO) proteins, a process termed SUMOylation, is involved in many fundamental cellular processes, SUMOylation is an important post-translational modification that is involved in many key biological processes, Group III metabotropic glutamate receptors (mGluRs) undergo post-translational modification by SUMO in in vitro assays but the SUMOylation of full-length mGluRs in mammalian cells has not been reported, SUMOylation is a relevant protein post-translational modification in eukaryotes. , However, the effects of pathogenic bacteria on SUMOylation, an essential post-translational modification in eukaryotic cells, remain largely unknown. , A novel post-translational modification of nucleolin, SUMOylation at Lys-294, mediates arsenite-induced cell death by regulating gadd45� mRNA stability., Drosophila Bicoid is a substrate of sumoylation and its activator function is subject to inhibition by this post-translational modification., Here, we demonstrate that SUMOylation of RelB might be one of these post-translational modifications rendering the function of the NF-�B transcription factor RelB. , In the last decade, SUMOylation has emerged as an essential post-translational modification in eukaryotes., SUMOylation, the conjugation of target proteins with SUMO (small ubiquitin-related modifier), is a type of post-translational modification in eukaryotes and involves the sequential action of activation (E1), conjugation (E2) and ligation (E3) enzymes., SUMOylation, the covalent attachment of a member of the small ubiquitin-like modifier (SUMO) family of proteins to lysines in target substrates, is an essential post-translational modification in eukaryotes., One way plants achieve this is through post-translational modification of target proteins by ubiquitination and SUMOylation., The small ubiquitin-like modifier (SUMO) pathway in eukaryotes is an essential post-translational modification required for a variety of cellular processes, development and organelle biogenesis., Post-translational modification by SUMO is a highly conserved pathway in eukaryotes that plays very important regulatory roles in many cellular processes., Many SUMOylated lysines have previously been reported to be ubiquitinated, acetylated or methylated, thus indicating cross-talk between SUMO and other post-translational modifications. We identified 70 phosphorylation and four acetylation events in proximity to SUMOylation sites, and we provide evidence for acetylation-dependent SUMOylation of endogenous histone H3. SUMOylation regulates target proteins involved in all nuclear processes including transcription, DNA repair, chromatin remodeling, precursor-mRNA splicing and ribosome assembly., SUMOylation is a reversible post-translational modification essential for genome stability. Using high-resolution MS, we have studied global SUMOylation in human cells in a site-specific manner, identifying a total of>4,300 SUMOylation sites in>1,600 proteins., We quantitatively studied SUMOylation dynamics in response to SUMO protease inhibition, proteasome inhibition and heat shock. Many SUMOylated lysines have previously been reported to be ubiquitinated, acetylated or methylated, thus indicating cross-talk between SUMO and other post-translational modifications. We identified 70 phosphorylation and four acetylation events in proximity to SUMOylation sites, and we provide evidence for acetylation-dependent SUMOylation of endogenous histone H3., Sumoylation is a post-translational modification shown to play a role in diverse biological processes. Here, we demonstrate that sumoylation is essential for proper heterochromatin function in Drosophila through modification of SU(VAR)3-7. Indeed, SU(VAR)3-7 is sumoylated at lysine K839; this modification is required for localization of SU(VAR)3-7 at pericentric heterochromatin, chromosome 4, and telomeres., Sumoylation is a post-translational modification shown to play a role in diverse biological processes. Here, we demonstrate that sumoylation is essential for proper heterochromatin function in Drosophila through modification of SU(VAR)3-7., Our results suggest a new level of regulation of Sall activity in vivo during animal development through post-translational modification by sumoylation., BACKGROUND: Small Ubiquitin-like MOdifier protein (SUMO) is a key regulator of nuclear functions but little is known regarding the role of the post-translational modification sumoylation outside of the nucleus, particularly in the Central Nervous System (CNS).METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that the expression levels of SUMO-modified substrates as well as the components of the sumoylation machinery are temporally and spatially regulated in the developing rat brain., SUMOylation in Giardia lamblia: A Conserved Post-Translational Modification in One of the Earliest Divergent Eukaryotes., Identification of a novel post-translational modification in Plasmodium falciparum: protein sumoylation in different cellular compartments., More recently, Akt has been identified as a substrate for many different post-translational modifications, including not only phosphorylation of other residues, but also acetylation, glycosylation, oxidation, ubiquitination and SUMOylation.[SEP]Relations: protein tag has relations: molfunc_protein with SUMO2, molfunc_protein with SUMO2, molfunc_protein with SUMO4, molfunc_protein with SUMO4, molfunc_protein with SUMO1, molfunc_protein with SUMO1, molfunc_protein with SUMO1P1, molfunc_protein with SUMO1P1, molfunc_protein with SUMO3, molfunc_protein with SUMO3. Definitions: Ubiquitin-like MOdifier protein defined as following: A molecular function exhibited by a protein that is covalently attached (AKA tagged or conjugated) to another protein where it acts as a marker, recognized by the cellular apparatus to target the tagged protein for some cellular process such as modification, sequestration, transport or degradation. [GOC:dos, GOC:go_curators, PMID:19028679, PMID:20054389, PMID:6305978]. E2 defined as following: Isoenergetic transfer of a ubiquitin-like protein (ULP) from one protein to another via the reaction X-SCP + Y -> Y-SCP + X, where both the X-SCP and Y-SCP linkages are thioester bonds between the C-terminal amino acid of SCP and a sulfhydryl side group of a cysteine residue. [GOC:dph]. chromosome 4 defined as following: A specific pair of GROUP B CHROMOSOMES of the human chromosome classification.. RelB defined as following: This gene is involved in transcriptional regulation of immune processes.. Akt defined as following: Expressed in diverse tissues, Protein Kinase B (AKT/RAC Family) is a group (Alpha, Beta and Gamma) of cytoplasmic serine/threonine enzymes that covalently transfer the terminal, gamma phosphate group from ATP to a variety of substrate proteins and regulate cell signaling responses to insulin, PDGF, and IGF1 (through PI3K) involved in cell survival, cell proliferation, differentiation, apoptosis, glycogen synthesis, and glucose uptake.. telomeres defined as following: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.. PML defined as following: An opportunistic viral infection of the central nervous system associated with conditions that impair cell-mediated immunity (e.g., ACQUIRED IMMUNODEFICIENCY SYNDROME and other IMMUNOLOGIC DEFICIENCY SYNDROMES; HEMATOLOGIC NEOPLASMS; IMMUNOSUPPRESSION; and COLLAGEN DISEASES). The causative organism is JC Polyomavirus (JC VIRUS) which primarily affects oligodendrocytes, resulting in multiple areas of demyelination. Clinical manifestations include DEMENTIA; ATAXIA; visual disturbances; and other focal neurologic deficits, generally progressing to a vegetative state within 6 months. (From Joynt, Clinical Neurology, 1996, Ch26, pp36-7). proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. eukaryotic cells defined as following: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. gadd45 defined as following: Human GADD45A wild-type allele is located within 1p31.2-p31.1 and is approximately 3 kb in length. This allele, which encodes growth arrest and DNA-damage-inducible protein GADD45 alpha, is involved in the modulation of cellular responses to environmental stress.. Plants defined as following: Multicellular, eukaryotic life forms of kingdom Plantae. Plants acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations. It is a non-taxonomical term most often referring to LAND PLANTS. In broad sense it includes RHODOPHYTA and GLAUCOPHYTA along with VIRIDIPLANTAE.. pericentric heterochromatin defined as following: Heterochromatin that is located adjacent to the CENP-A rich centromere 'central core' and characterized by methylated H3 histone at lysine 9 (H3K9me2/H3K9me3). [PMID:12019236, PMID:20206496, PMID:22729156, PMID:9413993]. eukaryotes defined as following: Organism or cells with a nucleus separated from the cytoplasm by a two membrance nuclear envelope and compartmentalization of function into distinct cytoplasmic organelles.. nucleolin defined as following: Nucleolin (710 aa, ~77 kDa) is encoded by the human NCL gene. This protein is involved in both chromatin decondensation and ribosome assembly.. modification defined as following:Respond with exceptions, completions and modifications or revisions done before completion
. nucleus defined as following: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). histone H3 defined as following: Histone H3 is a core subunit of the eukaryotic nucleosome complex. Histones are basic nuclear proteins responsible for the nucleosome structure of chromatin. Repeating nucleosome units contain two molecules each of Histones H2A, H2B, H3, and H4 that form an octamer complex around which approximately 146 base pairs of DNA is wrapped. Linker Histone H1 interacts with DNA between nucleosome units in mediating chromatin compaction into higher order structures. (NCI). ribosome defined as following: Multicomponent ribonucleoprotein structures found in the CYTOPLASM of all cells, and in MITOCHONDRIA, and PLASTIDS. They function in PROTEIN BIOSYNTHESIS via GENETIC TRANSLATION.. covalent defined as following: A physical connection between two atoms or radicals in which a chemical bond is formed by sharing electrons..", "label": "yes"} {"id": "converted_2561", "sentence1": "Has intepirdine been evaluated in clinical trials? (November 2017)", "sentence2": "Using small molecules blocking 5-HT6serotonin receptor (intepirdine), inhibiting BACE activity (E2609, AZD3293, and verubecestat), or reducing tau aggregation (TRx0237) are also currently in Phase III clinical trials.[SEP]Definitions: tau defined as following: A synthetic uridine pro-drug that is converted to uridine in vivo. Uridine, a pyrimidine nucleotide, has been used in a variety of diseases including depressive disorders and inherited myopathies. (NCI04).", "label": "yes"} {"id": "converted_3483", "sentence1": "Is Ubrogepant effective for migraine?", "sentence2": "CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks. , Despite the clear safety concerns, clinical trial data suggests that their intermittent use remains a viable and safe alternative, with 2 molecules remaining in clinical development (ubrogepant and rimegepant). , Two gepants, ubrogepant and rimegepant, have completed positive pivotal trials for acute treatment of migraine, but have not yet been submitted to the FDA for this indication., Two gepants, ubrogepant and rimegepant, have completed positive pivotal trials for the acute treatment of migraine, but have not yet been submitted to the FDA for this indication. , Area covered: This review reports on compounds currently under development for the oral treatment of acute migraine attacks, focusing on Calcitonin-Gene-Related-Peptide receptor antagonists, specifically ubrogepant and rimegepant. , Furthermore, new hope rises for the CGRP (calcitonin-gene related peptide)-antagonists, as the data for ubrogepant do not suggest hepatotoxicity but efficacy. , We applied this strategy for another late-stage clinical program: ubrogepant (MK-1602), a novel oral calcitonin gene-related peptide receptor antagonist for acute treatment of migraine. , A phase IIb randomized, double-blind, placebo-controlled trial of ubrogepant for the acute treatment of migraine., AIM: The aim of this trial was to evaluate the efficacy and tolerability of ubrogepant (MK-1602), a calcitonin gene-related peptide receptor antagonist (CGRP-RA), for the acute treatment of migraine., Ubrogepant 100 mg was significantly superior to placebo for two-hour pain freedom (25.5% vs 8.9%) but not for two-hour headache response., CONCLUSION: This trial supports ubrogepant's efficacy and provides further evidence that CGRP-RAs are viable options for the acute treatment of migraine., Meanwhile, 1 small-molecule CGRP receptor antagonist (ubrogepant, MK-1602) is currently in phase 3 studies for the acute treatment of migraine., CGRP receptor antagonists such as ubrogepant are effective for acute relief of migraine headache, whereas monoclonal antibodies against CGRP (eptinezumab, fremanezumab and galcanezumab) or the CGRP receptor (erenumab) effectively prevent migraine attacks., Recent findings\n\nCalcitonin gene-related peptide (CGRP) receptor antagonists (gepants-rimegepant and ubrogepant) and serotonin 5-HT __sub__ 1F __end_sub__ receptor agonists (ditans-lasmiditan) have completed phase 3 clinical trials and will soon offer novel, effective, well-tolerated nonvasoconstrictor options to treat acute migraine., We applied this strategy for another late-stage clinical program: ubrogepant (MK-1602), a novel oral calcitonin gene-related peptide receptor antagonist for acute treatment of migraine., Recently, orally administered next-generation small molecule CGRP-RAs have been shown to have safety and efficacy in acute treatment (ubrogepant and rimegepant) and prevention (atogepant) of migraine, giving additional CGRP-based therapeutic options for migraine patients., Ubrogepant 100 mg was significantly superior to placebo for two-hour pain freedom (25.5% vs 8.9%) but not for two-hour headache response., Lasmiditan, rimegepant and ubrogepant will extend our therapeutic armamentarium for managing acute migraine attacks when triptans are not effective or contraindicated due to cardiovascular disorders., Lasmiditan, rimegepant and ubrogepant will extend our therapeutic armamentarium for managing acute migraine attacks when triptans are not effective or contraindicated due to cardiovascular disorders., Lasmiditan, ubrogepant, and rimegepant are currently emerging acute migraine therapies that may be added to the arsenal of current migraine management., Ubrogepant for the Treatment of Migraine ., Ubrogepant 100 mg was significantly superior to placebo for two-hour pain freedom (25.5% vs 8.9%) but not for two-hour headache response., CONCLUSION\nThis trial supports ubrogepant's efficacy and provides further evidence that CGRP-RAs are viable options for the acute treatment of migraine., Ubrogepant (MK-1602) is a novel, oral, calcitonin gene-related peptide receptor antagonist in clinical development with positive Phase III outcomes for acute treatment of migraine., CONCLUSION: This trial supports ubrogepant's efficacy and provides further evidence that CGRP-RAs are viable options for the acute treatment of migraine., This trial supports ubrogepant's efficacy and provides further evidence that CGRP-RAs are viable options for the acute treatment of migraine., Ubrogepant for the Treatment of Migraine., Ubrogepant is an oral, small-molecule calcitonin gene-related peptide receptor antagonist for acute migraine treatment.[SEP]Relations: Ubrogepant has relations: drug_drug with Fosnetupitant, drug_drug with Fosnetupitant, drug_drug with Aprepitant, drug_drug with Aprepitant, drug_drug with Rimegepant, drug_drug with Rimegepant, drug_drug with Mibefradil, drug_drug with Mibefradil, drug_drug with Netupitant, drug_drug with Netupitant. Definitions: CGRP defined as following: A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.. monoclonal antibodies defined as following: Antibodies produced by a single clone of cells.. calcitonin gene-related peptide receptor antagonist defined as following: Pharmacologic agents that block NOCICEPTIVE PAIN signaling from CALCITONIN GENE-RELATED PEPTIDE RECEPTORS. They may be useful for the treatment of pain associated with MIGRAINE DISORDERS and OSTEOARTHRITIS.. Migraine defined as following: A common, severe type of vascular headache often associated with increased sympathetic activity, resulting in nausea, vomiting, and light sensitivity.. CGRP receptor defined as following: Cell surface proteins that bind CALCITONIN GENE-RELATED PEPTIDE with high affinity and trigger intracellular changes which influence the behavior of cells. CGRP receptors are present in both the CENTRAL NERVOUS SYSTEM and the periphery. They are formed via the heterodimerization of the CALCITONIN RECEPTOR-LIKE PROTEIN and RECEPTOR ACTIVITY-MODIFYING PROTEIN 1.. hepatotoxicity defined as following: Toxicity that impairs or damages the liver.. Area defined as following: The continents and countries situated on those continents; the UNITED STATES and each of the constituent states arranged by region; CANADA and each of its provinces; AUSTRALIA and each of its states; the major bodies of water and major islands on both hemispheres; and selected major cities.. molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. headache defined as following: The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.. agonists defined as following: Used with chemicals, drugs, and endogenous substances to indicate substances or agents that have affinity for a receptor and intrinsic activity at that receptor. (From Textbook of Pharmacology, 1991, p.16). cardiovascular disorders defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. triptans defined as following: Derivatives of TRYPTAMINES that are SEROTONIN RECEPTOR AGONISTS acting at 5-HT1 RECEPTORS. Some are used to treat MIGRAINE DISORDERS.. migraine defined as following: A common, severe type of vascular headache often associated with increased sympathetic activity, resulting in nausea, vomiting, and light sensitivity..", "label": "yes"} {"id": "converted_2264", "sentence1": "Does deflazacort have more side effects than prednisone?", "sentence2": "Though Deflazacort and prednisone improve clinical endpoints in Duchenne muscular dystrophy (DMD) patients, Deflazacort produces fewer side effects.[SEP]Relations: Deflazacort has relations: drug_drug with Prednisone, drug_drug with Prednisone, drug_drug with Prednisolone, drug_drug with Prednisolone, drug_drug with Meprednisone, drug_drug with Meprednisone, drug_drug with Prednylidene, drug_drug with Prednylidene, drug_drug with Methylprednisone, drug_drug with Methylprednisone. Definitions: Deflazacort defined as following: A synthetic glucocorticoid prodrug, with anti-inflammatory and immunomodulating properties. Upon administration, the active metabolite of deflazacort, 21-desacetyl deflazacort, binds to and activates tissue glucocorticoid receptors. This results in the inhibition of specific leukocyte functions and the inhibition of proinflammatory cytokine production.. DMD defined as following: An X-linked recessive muscle disease caused by an inability to synthesize DYSTROPHIN, which is involved with maintaining the integrity of the sarcolemma. Muscle fibers undergo a process that features degeneration and regeneration. Clinical manifestations include proximal weakness in the first few years of life, pseudohypertrophy, cardiomyopathy (see MYOCARDIAL DISEASES), and an increased incidence of impaired mentation. Becker muscular dystrophy is a closely related condition featuring a later onset of disease (usually adolescence) and a slowly progressive course. (Adams et al., Principles of Neurology, 6th ed, p1415). deflazacort defined as following: A synthetic glucocorticoid prodrug, with anti-inflammatory and immunomodulating properties. Upon administration, the active metabolite of deflazacort, 21-desacetyl deflazacort, binds to and activates tissue glucocorticoid receptors. This results in the inhibition of specific leukocyte functions and the inhibition of proinflammatory cytokine production.. prednisone defined as following: A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver..", "label": "no"} {"id": "converted_2129", "sentence1": "Is diphosphatidylglycerol (cardiolipin) a phospholipid of the mitochondrial membranes?", "sentence2": "A unique organelle for studying membrane biochemistry is the mitochondrion whose functionality depends on a coordinated supply of proteins and lipids. Mitochondria are capable of synthesizing several lipids autonomously such as phosphatidylglycerol, cardiolipin and in part phosphatidylethanolamine, phosphatidic acid and CDP-diacylglycerol., A small decrease of diphosphatidylglycerol also occurred in the hepatoma mitochondria inner membrane. , Diphosphatidylglycerol was confined to the mitochondrial fraction, where it represented about 7% of the total phosphoacylglycerols. , Mitochondrial membranes were isolated from the myocardium of young (4-month-old) and aged (33-month-old) male Long-Evans rats and compared in terms of cholesterol content and phospholipid and fatty acid composition. In aged rats, as compared to young, the major observations include: markedly higher cholesterol content; increased percentage of sphingomyelin and diphosphatidylglycerol (cardiolipin); , The polyglycerophosphatides (typified by diphosphatidylglycerol) were apparently synthesized in situ by intramitochondrial membrane-bound enzymes using CDP-diglycerides as intermediates. , Both the mitochondrial and microsomal fractions contained significant proportions of solvent front phospholipid (SFP) and whereas the mitochondrial SFP displayed the relatively unsaturated fatty acid composition characteristic of diphosphatidylglycerol (cardiolipin), the fatty acids of the microsomal SFP were distinctly more saturated., Ten to 15% of microsomal radioactive CDP-diglycerides was transferred to mitochondrial membranes and incorporated into mitochondrial radioactive lipids identified as phosphatidylglycerol, phosphatidylglycerophosphate, and, when [14C]linoleoyl CDP-diglycerides were used, diphosphatidylglycerol (cardiolipin)., The enzyme responsible for the conversion of phosphatidylglycerol to diphosphatidylglycerol (cardiolipin) in the presence of cytidine diphosphate diacylglycerol is firmly associated with mitochondrial membranes and is not extracted with hypotonic or hypertonic media or with nonionic detergents., The mechanism of cardiolipin (diphosphatidylglycerol) biosynthesis was examined in mitochondria and outer and inner mitochondrial membranes prepared from guinea pig and rat livers to determine whether this formation from phosphatidylglycerol was absolutely dependent on cytidinediphosphodiglyceride, as previously reported for intact mitochondria., In isolated mitochondrial outer membranes, cardiolipin (diphosphatidylglycerol) increased CPT1 activity 4-fold and the Km for carnitine 6-fold., Ten to 15% of microsomal radioactive CDP-diglycerides was transferred to mitochondrial membranes and incorporated into mitochondrial radioactive lipids identified as phosphatidylglycerol, phosphatidylglycerophosphate, and, when [14C]linoleoyl CDP-diglycerides were used, diphosphatidylglycerol (cardiolipin)., 90% or more of the phospholipid, cardiolipin was found in the mitochondrial membranes of wild type and petite yeast., Furthermore, the same mechanism for the biosynthesis of cardiolipin was operational in the outer and inner mitochondrial membranes., The mechanism of cardiolipin (diphosphatidylglycerol) biosynthesis was examined in mitochondria and outer and inner mitochondrial membranes prepared from guinea pig and rat livers to determine whether this formation from phosphatidylglycerol was absolutely dependent on cytidinediphosphodiglyceride, as previously reported for intact mitochondria, Cardiolipin (CL) is a key phospholipid in mitochondrial membranes, playing important roles in maintaining the functional integrity and dynamics of mitochondria in animals and yeasts, Cardiolipin, the specific phospholipid of mitochondria, is involved in the biogenesis, the dynamics, and the supramolecular organization of mitochondrial membranes, Cardiolipin (CL), the signature phospholipid of mitochondrial membranes, is crucial for both mitochondrial function and cellular processes outside of the mitochondria, Since it has been recognized that mitochondria are crucial not only for energy metabolism but also for other cellular functions, there has been a growing interest in cardiolipin, the specific phospholipid of mitochondrial membranes, Cardiolipin, the main anionic phospholipid in mitochondrial membranes, is expected to be a determinant in this adaptive mechanism since it modulates the activity of most membrane proteins, Ten to 15% of microsomal radioactive CDP-diglycerides was transferred to mitochondrial membranes and incorporated into mitochondrial radioactive lipids identified as phosphatidylglycerol, phosphatidylglycerophosphate, and, when [14C]linoleoyl CDP-diglycerides were used, diphosphatidylglycerol (cardiolipin), Cardiolipin is normally localized to the inner mitochondrial membrane; however, when cardiolipin becomes externalized to the surface of dysregulated mitochondria, it promotes inflammasome activation and stimulates the elimination of damaged or nonfunctional mitochondria by mitophagy, In isolated mitochondrial outer membranes, cardiolipin (diphosphatidylglycerol) increased CPT1 activity 4-fold and the Km for carnitine 6-fold. , Increasing levels of cardiolipin differentially influence packing of phospholipids found in the mitochondrial inner membrane., Here, we used Saccharomyces cerevisiae subjected to conditions that affect mitochondrial metabolism as a model to determine the possible role of cardiolipin in stress adaptation. , This decline of respiration was attributed to a progressive diminution of the number of mitochondria in copper-treated cells, based on the demonstration of the concomitant decline of (1) cardiolipin (diphosphatidylglycerol) and cytochrome aa3 (cytochrome oxidase), two specific markers of mitochondrial inner membrane, and (2) fumarase activity, a specific marker of mitochondrial matrix space., Diphosphatidylglycerol (DPG) or cardiolipin, a specific component of the inner mitochondrial membrane, represents about 4% of the total lipid content., Experimental results confirmed that the biosynthesis of cardiolipin, from the membrane-bound radioactive phosphatidylglycerol in intact mitochondria isolated from guinea pig and rat liver, was absolutely dependent on CDP-diglycerides and required the addition of divalent cations., We have shown that decrease of cardiolipin in mitochondrial membrane occurs early during ischemia, and only during the irreversible phase of ischemia are phosphatidylethanolamine and phosphatidylcholine broken down., Partial purification of diphosphatidylglycerol synthetase from liver mitochondrial membranes., A small decrease of diphosphatidylglycerol also occurred in the hepatoma mitochondria inner membrane.[SEP]Relations: mitochondrial inner membrane has relations: cellcomp_protein with PHB, cellcomp_protein with PHB, cellcomp_protein with PMPCB, cellcomp_protein with PMPCB. mitochondrial membrane has relations: cellcomp_protein with CARD19, cellcomp_protein with CARD19, cellcomp_protein with ACADL, cellcomp_protein with ACADL. mitochondrial outer membrane has relations: cellcomp_protein with BNIP3L, cellcomp_protein with BNIP3L. Definitions: lipids defined as following: A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed). sphingomyelin defined as following: A class of sphingolipids found largely in the brain and other nervous tissue. They contain phosphocholine or phosphoethanolamine as their polar head group so therefore are the only sphingolipids classified as PHOSPHOLIPIDS.. ischemia defined as following: A surgical procedure during which the blood supply to an organ or tissue is interrupted and then later reestablished.. phospholipids defined as following: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.. organelle defined as following: Cell part which consists of macromolecules aggregated into discrete structures in the protoplasm. (Digital Anatomist Foundational Model). phosphatidylethanolamine defined as following: A phospholipid with the polar ethanolamine found in phosphoester linkage to diacylglycerol.. mitochondria defined as following: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed). Mitochondrial membranes defined as following: Either of the lipid bilayers that surround the mitochondrion and form the mitochondrial envelope. [GOC:mah, NIF_Subcellular:sao1045389829]. divalent cations defined as following: Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis.. wild type defined as following: A finding indicating that no genetic variations have been detected across the entire sequence of one or more genes.. hepatoma defined as following: Tumors or cancer of the LIVER.. cytidine diphosphate defined as following: Cytidine 5'-(trihydrogen diphosphate). A cytosine nucleotide containing two phosphate groups esterified to the sugar moiety. Synonyms: CRPP; cytidine pyrophosphate.. cholesterol defined as following: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.. Cardiolipin defined as following: Acidic phospholipids composed of two molecules of phosphatidic acid covalently linked to a molecule of glycerol. They occur primarily in mitochondrial inner membranes and in bacterial plasma membranes. They are the main antigenic components of the Wassermann-type antigen that is used in nontreponemal SYPHILIS SERODIAGNOSIS.. cytochrome oxidase defined as following: A multisubunit enzyme complex containing CYTOCHROME A GROUP; CYTOCHROME A3; two copper atoms; and 13 different protein subunits. It is the terminal oxidase complex of the RESPIRATORY CHAIN and collects electrons that are transferred from the reduced CYTOCHROME C GROUP and donates them to molecular OXYGEN, which is then reduced to water. The redox reaction is simultaneously coupled to the transport of PROTONS across the inner mitochondrial membrane.. CPT1 defined as following: Human CPT1A wild-type allele is located in the vicinity of 11q13.3 and is approximately 90 kb in length. This allele, which encodes carnitine O-palmitoyltransferase 1, liver isoform protein, plays a role in the modification and mitochondrial uptake of long-chain fatty acids and the metabolism of triglycerides by the liver. Loss of function mutations of the gene are associated with carnitine palmitoyltransferase 1A deficiency.. membrane proteins defined as following: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.. fatty acids defined as following: Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed). proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. CDP-diacylglycerol defined as following: The ester of diacylglycerol with the terminal phosphate of cytidine diphosphate. It serves as an intermediate in the biosynthesis of phosphatidylethanolamine and phosphatidylserine in bacteria.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. saturated defined as following: Impregnation of one substance by another to the greatest possible extent; that concentration of a dissolved substance that cannot be exceeded.. phosphatidic acid defined as following: A glycerol backbone covalently bound to a phosphate group in one position, and fatty acids in the 2nd and 3rd positions. Phosphatidic acids thus have a polar head and apolar tails, and occur in cell membranes throughout nature.. cytochrome aa3 defined as following: A dimer of CYTOCHROME A and CYTOCHROME A3.. mitochondrial inner membrane defined as following: The inner, i.e. lumen-facing, lipid bilayer of the mitochondrial envelope. It is highly folded to form cristae. [GOC:ai]. guinea pig defined as following: The domesticated guinea pig, Cavia porcellus.. mitochondrial defined as following: The distribution of mitochondria, including the mitochondrial genome, into daughter cells after mitosis or meiosis, mediated by interactions between mitochondria and the cytoskeleton. [GOC:mcc, PMID:10873824, PMID:11389764]. membrane defined as following: Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures.. myocardium defined as following: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.. mitochondrial outer membranes defined as following: The outer, i.e. cytoplasm-facing, lipid bilayer of the mitochondrial envelope. [GOC:ai]. diacylglycerol defined as following: A synthetic oil with anti-obesity activity. The enzymatically synthesized isoform, 1,3-isoform diacylglycerol, is suggested to decrease formation of chylomicrons as well as shunting them directly to the liver through the portal vein where they are oxidized. Increased beta-oxidation may enhance body weight loss, suppress body fat accumulation and lower serum triacylglycerol levels through increasing satiety.. mitochondrial membranes defined as following: Either of the lipid bilayers that surround the mitochondrion and form the mitochondrial envelope. [GOC:mah, NIF_Subcellular:sao1045389829]. phospholipid defined as following: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.. cardiolipin defined as following: Acidic phospholipids composed of two molecules of phosphatidic acid covalently linked to a molecule of glycerol. They occur primarily in mitochondrial inner membranes and in bacterial plasma membranes. They are the main antigenic components of the Wassermann-type antigen that is used in nontreponemal SYPHILIS SERODIAGNOSIS..", "label": "yes"} {"id": "converted_3682", "sentence1": "Is indinavir effective for treatment of amyotrophic lateral sclerosis?", "sentence2": "Group differences in the rate of decline were not significant between the groups for the ALS Functional Rating Scale (p = 0.36) or for the secondary variables. The toxicity and negative efficacy trends discourage further indinavir trials in ALS.[SEP]Relations: amyotrophic lateral sclerosis has relations: disease_protein with INA, disease_protein with INA, disease_protein with ANG, disease_protein with ANG, disease_protein with XIAP, disease_protein with XIAP, disease_disease with progressive muscular atrophy, disease_disease with progressive muscular atrophy, disease_protein with VIM, disease_protein with VIM. Definitions: toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. ALS defined as following: A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94). indinavir defined as following: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability.. amyotrophic lateral sclerosis defined as following: An inherited form of amyotrophic lateral sclerosis, usually inherited in an autosomal dominant pattern, caused by mutation(s) in the SOD1 gene, encoding superoxide dismutase..", "label": "no"} {"id": "converted_1507", "sentence1": "Do thyroid hormone receptors change after brain injury?", "sentence2": "For example, the T3 receptor alpha was predominantly expressed in stroke-tissue, indicating that regeneration of nerves in stroke tissue may be facilitated by increased T3 receptor alpha expression., TRα expression was also increased in human infants with IVH. , Thus, in infants with IVH the combined elevation in deiodinase-3 and reduction in deiodinase-2 decreases TH signaling that can be worsened by an increase in unliganded TRα. , A rapid increase of the total number of binding sites for T3 appeared within 30 min of ischemia and reached over 40% by 3 h. During the same 3-h period, the relative binding affinity was reduced by 25%. Upon recirculation after 30 min or 3 h of ischemia, a rapid reversal of measured T3 binding sites occurred, which progressed to 20-30% below the control value by the recirculation period of 3 h. [SEP]Relations: siRNA binding has relations: molfunc_protein with FMR1, molfunc_protein with FMR1, molfunc_protein with TLR7, molfunc_protein with TLR7, molfunc_protein with AGO2, molfunc_protein with AGO2, molfunc_protein with TLR9, molfunc_protein with TLR9, molfunc_protein with TARBP2, molfunc_protein with TARBP2. Definitions: binding sites defined as following: The parts of a macromolecule that directly participate in its specific combination with another molecule.. ischemia defined as following: A surgical procedure during which the blood supply to an organ or tissue is interrupted and then later reestablished.. human defined as following: Members of the species Homo sapiens.. brain injury defined as following: Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.. thyroid hormone defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs..", "label": "yes"} {"id": "converted_4485", "sentence1": "Is nerinetide effective for ischaemic stroke?", "sentence2": "337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. , INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo., patients receiving alteplase. Serious adverse events occurred equally between groups.INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo.FUNDING: Canadian Inst[SEP]Relations: Alteplase has relations: drug_drug with Lenalidomide, drug_drug with Lenalidomide, drug_drug with Benzthiazide, drug_drug with Benzthiazide, drug_drug with Mebutizide, drug_drug with Mebutizide, drug_drug with Nimesulide, drug_drug with Nimesulide, drug_drug with Nelarabine, drug_drug with Nelarabine. Definitions: alteplase defined as following: A proteolytic enzyme in the serine protease family found in many tissues which converts PLASMINOGEN to FIBRINOLYSIN. It has fibrin-binding activity and is immunologically different from UROKINASE-TYPE PLASMINOGEN ACTIVATOR. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases.. ischaemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue..", "label": "no"} {"id": "converted_3543", "sentence1": "Does an interferon (IFN) signature exist for SLE patients?", "sentence2": "Interferon regulatory factor 7 activation correlates with the IFN signature and recurrent disease., In SLE post-transplant, recurrent disease activity and induction of IRF7 protein expression correlated with activation of the IFN signature., JAK inhibitor has the amelioration effect in lupus-prone mice: the involvement of IFN signature gene downregulation., We also detected decreased expression of several IFN-signature genes Ifit3 and Isg15 in CD4+ from SLE-prone mice following TOFA and DEXA treatment, and IFIT3 in CD3+ T cells from human patients following immunosuppressant therapy including steroid, respectively, We found that cDCs from prediseased TCSle male mice express the IFN signature as female TCSle cDCs do. Estrogens are necessary but not sufficient to express this IFN signature, but high doses of E2 can compensate for other steroidal components., Conventional DCs from Male and Female Lupus-Prone B6.NZM Sle1/Sle2/Sle3 Mice Express an IFN Signature and Have a Higher Immunometabolism That Are Enhanced by Estrogen., Type I IFN signature in childhood-onset systemic lupus erythematosus, Interferon type I (IFN-I) plays a pivotal role in the pathogenesis of SLE. , The IFN-I score (positive or negative), as a measure of IFN-I activation, was assessed using real-time quantitative PCR (RT-PCR) expression values of IFN-I signature genes (IFI44, IFI44L, IFIT1, Ly6e, MxA, IFITM1) in CD14+ monocytes of cSLE patients and healthy controls (HCs)[SEP]Relations: Human interferon beta has relations: drug_protein with IFNAR1, drug_protein with IFNAR1, drug_drug with Aminophylline, drug_drug with Aminophylline, drug_drug with Fenethylline, drug_drug with Fenethylline, drug_drug with Proxyphylline, drug_drug with Proxyphylline, drug_drug with 8-chlorotheophylline, drug_drug with 8-chlorotheophylline. Definitions: Isg15 defined as following: This gene is involved in both protein tagging and cell signaling.. IFI44 defined as following: This gene may play a role in the response to viral infection.. IFITM1 defined as following: Interferon-induced transmembrane protein 1 (125 aa, ~14 kDa) is encoded by the human IFITM1 gene. This protein is involved in interferon-induced antiviral responses.. steroid defined as following: A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed). MxA defined as following: Human MX1 wild-type allele is located in the vicinity of 21q22.3 and is approximately 39 kb in length. This allele, which encodes interferon-induced GTP-binding protein Mx1, is involved in the regulation of apoptosis, hydrolysis of GTP, the modulation of interferon-regulated signaling.. E2 defined as following: Isoenergetic transfer of a ubiquitin-like protein (ULP) from one protein to another via the reaction X-SCP + Y -> Y-SCP + X, where both the X-SCP and Y-SCP linkages are thioester bonds between the C-terminal amino acid of SCP and a sulfhydryl side group of a cysteine residue. [GOC:dph]. Interferon type I defined as following: Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).. Interferon regulatory factor 7 defined as following: This gene plays a role in the modulation of the innate immune response against DNA and RNA viruses.. IFIT1 defined as following: Interferon-induced protein with tetratricopeptide repeats 1 (478, ~55 kDa) is encoded by the human IFIT1 gene. This protein plays a role in binding to triphosphorylated, single-stranded viral RNA.. monocytes defined as following: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.. Ly6e defined as following: Human LY6E wild-type allele is located in the vicinity of 8q24.3 and is approximately 4 kb in length. This allele, which encodes lymphocyte antigen Ly-6E protein, is involved in myelopoiesis and signal transduction.. JAK defined as following: A family of intracellular tyrosine kinases that participate in the signaling cascade of cytokines by associating with specific CYTOKINE RECEPTORS. They act upon STAT TRANSCRIPTION FACTORS in signaling pathway referred to as the JAK/STAT pathway. The name Janus kinase refers to the fact the proteins have two phosphate-transferring domains.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. DCs defined as following: Neutral lipid storage disease (NLSD) refers to a group of diseases characterized by a deficit in the degradation of cytoplasmic triglycerides and their accumulation in cytoplasmic lipid vacuoles in most tissues of the body. The group is heterogeneous: currently cases of NLSD with icthyosis (NLSDI/Dorfman-Chanarin disease; see this term) and NLSD with myopathy (NLSDM/neutral lipid storage myopathy; see this term) can be distinguished.. IFN defined as following: Human interferons have been classified into 3 groups: alpha, beta, and gamma. Both alpha- and beta-IFNs, previously designated type I, are acid-stable, but they differ immunologically and in regard to some biologic and physiochemical properties. The IFNs produced by virus-stimulated leukocytes (leukocyte IFNs) are predominantly of the alpha type. Those produced by lymphoblastoid cells are about 90% alpha and 10% beta. Induced fibroblasts produce mainly or exclusively the beta type. The alpha- and beta-IFNs differ widely in amino acid sequence. The gamma or immune IFNs, which are produced by T lymphocytes in response to mitogens or to antigens to which they are sensitized, are acid-labile and serologically distinct from alpha- and beta-IFNs. (from OMIM 147570). CD14 defined as following: Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including MONOCYTES; MACROPHAGES; and some GRANULOCYTES. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein.. SLE defined as following: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.. DEXA defined as following: A technique for scanning bone and measuring bone mineral density (BMD). A DXA scanner produces 2 X-ray beams, each with different energy levels. One beam is high energy while the other is low energy. The amount of x-rays that pass through the bone is measured for each beam. This will vary depending on the thickness of the bone. Based on the difference between the 2 beams, the bone density can be measured.. human defined as following: Members of the species Homo sapiens..", "label": "yes"} {"id": "converted_2947", "sentence1": "Are there tools for reviewing variant calls?", "sentence2": "VIPER: a web application for rapid expert review of variant calls., With the rapid development in next-generation sequencing, cost and time requirements for genomic sequencing are decreasing, enabling applications in many areas such as cancer research. Many tools have been developed to analyze genomic variation ranging from single nucleotide variants to whole chromosomal aberrations. As sequencing throughput increases, the number of variants called by such tools also grows. Often employed manual inspection of such calls is thus becoming a time-consuming procedure. We developed the Variant InsPector and Expert Rating tool (VIPER) to speed up this process by integrating the Integrative Genomics Viewer into a web application. Analysts can then quickly iterate through variants, apply filters and make decisions based on the generated images and variant metadata. VIPER was successfully employed in analyses with manual inspection of more than 10 000 calls.Availability and implementation: VIPER is implemented in Java and Javascript and is freely available at https://github.com/MarWoes/viper., Variant Review with the Integrative Genomics Viewer., VIPER: a web application for rapid expert review of variant calls.Supplementary data are available at Bioinformatics online., We developed the Variant InsPector and Expert Rating tool (VIPER) to speed up this process by integrating the Integrative Genomics Viewer into a web application.[SEP]Definitions: variants defined as following: An alteration or difference from a norm or standard..", "label": "yes"} {"id": "converted_2190", "sentence1": "Is there an association between Histone H3.3 mutations and glioma?", "sentence2": "PURPOSE: Histone H3.3 (H3F3A) mutation in the codon for lysine 27 (K27M) has been found as driver mutations in pediatric glioblastoma and has been suggested to play critical roles in the pathogenesis of thalamic gliomas and diffuse intrinsic pontine gliomas. We report a case of thalamic glioma with H3F3A K27M mutation, which was detected in both the primary tumor diagnosed as diffuse astrocytoma obtained during the first surgery and also in the tumor diagnosed as anaplastic astrocytoma obtained at the second surgery., CONCLUSION: This report demonstrates minute neuroradiological and pathological features of malignant transformation from thalamic low grade glioma with H3F3A K27M mutation., Recently, sequencing of tumor cells revealed that histone H3 is frequently mutated in pediatric HGG, with up to 78 % of diffuse intrinsic pontine gliomas (DIPGs) carrying K27M and 36 % of non-brainstem gliomas carrying either K27M or G34R/V mutations., The pathological diagnosis was anaplastic oligodendroglioma, and we identified a mutation in histone H3.3 in the tumor specimen., CONCLUSIONS: Pediatric brainstem oligodendroglial tumors can include histone H3.3-mutated tumors and have a tendency to disseminate throughout the neuroaxis at the time of relapse., We highlight the genetic aberrations recently discovered in isocitrate dehydrogenase, alpha thalassemia/mental retardation syndrome X-linked, death-domain-associated protein, histone H3.3, and telomerase reverse transcriptase and discuss how these mutations lead to unexpected changes in the epigenetic landscape in gliomas., Particularly striking is the discovery of frequent histone H3.3 mutations in pediatric glioma, a particularly aggressive neoplasm that has long remained poorly understood, Exon sequencing has identified a mutation in K27M of the histone H3.3 gene (H3F3A K27M and G34R/V) in about 20% of pediatric glioblastomas, but it remains to be seen whether these mutations can be considered specific for pediatric diffuse high-grade astrocytomas or also occur in other pediatric brain tumors, The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression, A lesson learned from the H3.3K27M mutation found in pediatric glioma: a new approach to the study of the function of histone modifications in vivo, Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH)1 mutation with a DNA methylation signature., Over 70% of diffuse intrinsic pediatric gliomas, an aggressive brainstem tumor, harbor heterozygous mutations that create a K27M amino acid substitution (methionine replaces lysine 27) in the tail of histone H3.3., Mutations in H3F3A, which encodes histone H3.3, commonly occur in pediatric glioblastoma., Somatic mutations of the H3F3A and HIST1H3B genes encoding the histone H3 variants, H3.3 and H3.1, were recently identified in high-grade gliomas arising in the thalamus, pons and spinal cord of children and young adults., K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas., Recurrent mutations affecting the histone H3.3 residues Lys27 or indirectly Lys36 are frequent drivers of pediatric high-grade gliomas (over 30% of HGGs)., Use of human embryonic stem cells to model pediatric gliomas with H3.3K27M histone mutation., Recent studies on high-grade pediatric GBM have identified two recurrent mutations (K27M and G34R/V) in genes encoding histone H3 (H3F3A for H3.3 and HIST1H3B for H3.1)., Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma.[SEP]Relations: histone H3 acetylation has relations: bioprocess_protein with MAP3K7, bioprocess_protein with MAP3K7, bioprocess_protein with KAT7, bioprocess_protein with KAT7, bioprocess_protein with BRPF3, bioprocess_protein with BRPF3, bioprocess_protein with KAT2A, bioprocess_protein with KAT2A, bioprocess_protein with KAT6A, bioprocess_protein with KAT6A. Definitions: H3.1 defined as following: This gene is involved in the regulation of chromosome dynamics.. isocitrate dehydrogenase defined as following: An enzyme of the oxidoreductase class that catalyzes the conversion of isocitrate and NAD+ to yield 2-ketoglutarate, carbon dioxide, and NADH. It occurs in cell mitochondria. The enzyme requires Mg2+, Mn2+; it is activated by ADP, citrate, and Ca2+, and inhibited by NADH, NADPH, and ATP. The reaction is the key rate-limiting step of the citric acid (tricarboxylic) cycle. (From Dorland, 27th ed) (The NADP+ enzyme is EC 1.1.1.42.) EC 1.1.1.41.. histone modifications defined as following: The covalent alteration of one or more amino acid residues within a histone protein. [GOC:krc]. anaplastic oligodendroglioma defined as following: A central nervous system tumor with morphological features of anaplastic oligodendroglioma in which there is insufficient information on the IDH genes and 1p/19q codeletion status.. glioblastoma multiforme defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO). genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. gliomas defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21). Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. spinal cord defined as following: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.. astrocytoma defined as following: Neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors. Fibrillary astrocytomas are the most common type and may be classified in order of increasing malignancy (grades I through IV). In the first two decades of life, astrocytomas tend to originate in the cerebellar hemispheres; in adults, they most frequently arise in the cerebrum and frequently undergo malignant transformation. (From Devita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2013-7; Holland et al., Cancer Medicine, 3d ed, p1082). histone H3 defined as following: Histone H3 is a core subunit of the eukaryotic nucleosome complex. Histones are basic nuclear proteins responsible for the nucleosome structure of chromatin. Repeating nucleosome units contain two molecules each of Histones H2A, H2B, H3, and H4 that form an octamer complex around which approximately 146 base pairs of DNA is wrapped. Linker Histone H1 interacts with DNA between nucleosome units in mediating chromatin compaction into higher order structures. (NCI). HIST1H3B defined as following: Human H3C2 wild-type allele is located in the vicinity of 6p22.1 and is approximately 1 kb in length. This allele, which encodes histone H3.1 protein, plays a role in the modulation of chromatin structure.. pons defined as following: The front part of the hindbrain (RHOMBENCEPHALON) that lies between the MEDULLA and the midbrain (MESENCEPHALON) ventral to the cerebellum. It is composed of two parts, the dorsal and the ventral. The pons serves as a relay station for neural pathways between the CEREBELLUM to the CEREBRUM.. codon defined as following: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).. anaplastic astrocytoma defined as following: A central nervous system tumor with morphological features of anaplastic astrocytoma in which there is insufficient information on the IDH genes status.. methionine defined as following: A preparation of METHIONINE that includes a mixture of D-methionine and L-methionine isomers.. thalamus defined as following: Paired bodies containing mostly GRAY MATTER and forming part of the lateral wall of the THIRD VENTRICLE of the brain.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. histone H3.3 gene defined as following: This gene plays a role in nucleosome assembly.. GBM defined as following: A sheet of amorphous extracellular material upon which the basal surfaces of epithelial cells rest and is the covering surface of a glomerular capillary, interposed between the cellular elements and the underlying connective tissue.. H3F3A defined as following: Human H3-3A wild-type allele is located in the vicinity of 1q42.12 and is approximately 10 kb in length. This allele, which encodes histone H3.3 protein, plays a role in both nucleosome assembly and transcriptional regulation.. tumor cells defined as following: Cells of, or derived from, a tumor.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. telomerase reverse transcriptase defined as following: This gene is involved in cell cycle regulation and telomere maintenance.. variants defined as following: An alteration or difference from a norm or standard.. H3K27 defined as following: The lysine residue found at amino acid position 28 in the histone H3 protein. Methylation of this residue may be a marker for transcriptionally repressed genes.. human embryonic stem cells defined as following: A type of PLURIPOTENT STEM CELLS derived from early stage human embryos, up to and including the BLASTOCYST stage.. glioma defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21).", "label": "yes"} {"id": "converted_2265", "sentence1": "Does echinacea increase anaphylaxis risk?", "sentence2": "Chicoric acid (dicaffeoyl-tartaric acid), is a natural phenolic compound found in a number of plants, such as chicory (Cichorium intybus) and Echinacea (Echinacea purpurea), which possesses antioxidant, anti-inflammatory, antiviral, and analgesic activities. Although these biological effects of chicoric acid have been investigated, there are no reports of its antiallergic-related anti-inflammatory effects in human mast cells (HMC)-1 or anaphylactic activity in a mouse model., BACKGROUND: Fifty percent of Australians use complementary and alternative medicines (other than vitamins) in any 12-month period, of which echinacea-containing products are increasingly popular. Recent reports have highlighted the risk of allergic reactions to complementary medicines in atopic patients., Two patients suffered anaphylaxis and a third had an acute asthma attack 10 minutes after their first ever dose of echinacea., Fifty-one Australian adverse drug reports implicating echinacea were also reviewed. There were 26 cases suggestive of possible immunoglobulin E-mediated hypersensitivity (4 anaphylaxis, 12 acute asthma, 10 urticaria/angioedema). , Echinacea-associated anaphylaxis., A woman with atopy experienced anaphylaxis after taking, among other dietary supplements, a commercial extract of echinacea., Risk of anaphylaxis in complementary and alternative medicine., Several culprits identified including Andrographis paniculata, Echinacea species, bee products, Ginkgo biloba and Ginseng are discussed here.SUMMARY: Knowing the factors that increase the risk of anaphylaxis allows reactions to be recognized, reported and further investigated.[SEP]Relations: anaphylaxis has relations: disease_disease with exercise-induced anaphylaxis, disease_disease with exercise-induced anaphylaxis, contraindication with Paclitaxel, contraindication with Paclitaxel, contraindication with Esmolol, contraindication with Esmolol, contraindication with Acebutolol, contraindication with Acebutolol, contraindication with Atenolol, contraindication with Atenolol. Definitions: allergic reactions defined as following: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.. anaphylaxis defined as following: Progression of anaphylaxis into systemic shock, which is characterized by significant reduction in tissue perfusion which leads to hypoxia and hypotension, and can lead to death if untreated.. atopic defined as following: A genetic predisposition to form IgE antibodies in response to exposure to allergens and therefore, for the development of immediate (type I) hypersensitivity and atopic conditions, such as allergic rhinitis; bronchial asthma, atopic dermatitis, and food allergy. Mutations of specific alleles on the long arm of chromosome 5 have been associated with higher levels of IL-4 and IgE and are known as IL-4 promoter polymorphisms.. atopy defined as following: Human MS4A2 wild-type allele is located within 11q12-q13 and is approximately 10 kb in length. This allele, which encodes high affinity immunoglobulin epsilon receptor subunit beta protein, plays a role in both immunoglobulin binding and mast cell responses..", "label": "yes"} {"id": "converted_1165", "sentence1": "Are there currently applications of deep learning in genomics?", "sentence2": "Deep learning of the tissue-regulated splicing code., Using a deep neural network, we developed a model inferred from mouse RNA-Seq data that can predict splicing patterns in individual tissues and differences in splicing patterns across tissues. Our architecture uses hidden variables that jointly represent features in genomic sequences and tissue types when making predictions. A graphics processing unit was used to greatly reduce the training time of our models with millions of parameters., We show that the deep architecture surpasses the performance of the previous Bayesian method for predicting AS patterns. With the proper optimization procedure and selection of hyperparameters, we demonstrate that deep architectures can be beneficial, even with a moderately sparse dataset. An analysis of what the model has learned in terms of the genomic features is presented., Machine learning applications in genetics and genomics[SEP]Relations: learning has relations: bioprocess_protein with APP, bioprocess_protein with APP, bioprocess_protein with ARC, bioprocess_protein with ARC, bioprocess_bioprocess with associative learning, bioprocess_bioprocess with associative learning, bioprocess_bioprocess with learning or memory, bioprocess_bioprocess with learning or memory, bioprocess_protein with JUN, bioprocess_protein with JUN. Definitions: tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. Machine learning defined as following: A type of ARTIFICIAL INTELLIGENCE that enable COMPUTERS to independently initiate and execute LEARNING when exposed to new data..", "label": "yes"} {"id": "converted_2709", "sentence1": "Is lumican a secreted protein?", "sentence2": "fibroblasts stimulated with the fibrocyte-secreted inflammatory signal tumor necrosis factor-α secrete the small leucine-rich proteoglycan lumican, TNF-α-stimulated fibroblasts secrete lumican to promote fibrocyte differentiation., Secreted 70kDa lumican stimulates growth and inhibits invasion of human pancreatic cancer., the elevated level of lumican secretion to extracellular space leads to actin cytoskeletal remodeling followed by an increase in migration capacity of human colon LS180 cells, Lumican is a secreted proteoglycan that regulates collagen fibril assembly., This is the first time that the synthesis and secretion of lumican in human melanoma cell lines is reported. [SEP]Relations: Protein S human has relations: drug_drug with Lumiracoxib, drug_drug with Lumiracoxib, drug_drug with Pentosan polysulfate, drug_drug with Pentosan polysulfate, drug_drug with Urokinase, drug_drug with Urokinase. extracellular space has relations: cellcomp_protein with LUM, cellcomp_protein with LUM. ECM proteoglycans has relations: pathway_protein with LUM, pathway_protein with LUM. Definitions: collagen defined as following: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).. lumican defined as following: Lumican (338 aa, ~38 kDa) is encoded by the human LUM gene. This protein is involved in the structure of interstitial collagen matrices.. fibrocyte defined as following: A quiescent connective tissue cell with minimal cytoplasm and little to no evidence of protein synthesis. These cells may be able to differentiate into fibroblasts.. human defined as following: Members of the species Homo sapiens.. proteoglycan defined as following: Glycoproteins which have a very high polysaccharide content.. extracellular space defined as following: Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall.. actin defined as following: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle..", "label": "yes"} {"id": "converted_767", "sentence1": "Is tubulin acetylation involved in cell motility?", "sentence2": "In this study, we found that paclitaxel induced tubulin acetylation in endothelial and tumor cells, at concentrations that affected cell motility but not proliferation (10(-8) to 10(-9) M, for 4 hours). Induction of tubulin acetylation correlated with inhibition of motility but not proliferation based on a comparison of highly and poorly cytotoxic taxanes (paclitaxel and IDN5390) and tumor cell lines sensitive and resistant to paclitaxel (1A9 and 1A9 PTX22)., we found that overexpression of the tubulin deacetylase SIRT2 increased cell motility and reduced cell response to the anti-motility activity of paclitaxel. Conversely, the SIRT2 inhibitor splitomicin reduced cell motility and potentiated the anti-motility activity of paclitaxel. The inhibitory effect was further potentiated by the addition of the HDAC6 inhibitor trichostatin A., Cell motility and adhesion involves dynamic microtubule (MT) acetylation/deacetylation, a process regulated by enzymes as HDAC6, a major cytoplasmic α-tubulin deacetylase., GRK2 and HDAC6 colocalize in the lamellipodia of migrating cells, leading to local tubulin deacetylation and enhanced motility., This review highlights the emerging roles of tubulin acetylation in multiple cellular functions, ranging from cell motility, cell cycle progression or cell differentiation to intracellular trafficking and signalling., Our results indicate that TPPP/p25 binds to HDAC6 (histone deacetylase 6), an enzyme responsible for tubulin deacetylation. Moreover, we demonstrated that the direct interaction of these two proteins resulted in the inhibition of the deacetylase activity of HDAC6., Finally, we demonstrated that, similarly to other HDAC6 inhibitors, TPPP/p25 influences the microtubule dynamics by decreasing the growth velocity of the microtubule plus ends and also affects cell motility as demonstrated by time lapse video experiments., \"tubacin,\" which inhibits alpha-tubulin deacetylation in mammalian cells., We provide evidence that class II histone deacetylase 6 (HDAC6) is the intracellular target of tubacin., Tubacin treatment did not affect the stability of microtubules but did decrease cell motility., They also suggest that small molecules that selectively inhibit HDAC6-mediated alpha-tubulin deacetylation, a first example of which is tubacin, might have therapeutic applications as antimetastatic and antiangiogenic agents., Furthermore, overexpression of HDAC6 promotes chemotactic cell movement, supporting the idea that HDAC6-mediated deacetylation regulates microtubule-dependent cell motility., HDAC6 is a major cytoplasmic a-tubulin deacetylase that is involved in cell motility and adhesion. GRK2 dynamically and directly associates with and phosphorylates HDAC6 to stimulate its a-tubulin deacetylase activity at specific cellular localizations, such as the leading edge of migrating cells, thus promoting local tubulin deacetylation and enhanced motility.[SEP]Relations: tubulin binding has relations: molfunc_protein with ALDOA, molfunc_protein with ALDOA, molfunc_protein with TTLL2, molfunc_protein with TTLL2, molfunc_protein with TTLL12, molfunc_protein with TTLL12, molfunc_protein with TTLL4, molfunc_protein with TTLL4, molfunc_protein with MAP1A, molfunc_protein with MAP1A. Definitions: tubulin defined as following: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from SPERM FLAGELLUM; CILIA; and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to COLCHICINE; VINCRISTINE; and VINBLASTINE.. microtubules defined as following: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.. HDAC6 defined as following: This gene is involved in chromatin remodeling, repression of gene expression and cellular management of misfolded protein-induced stress.. SIRT2 defined as following: A sirtuin family member found primarily in the CYTOPLASM. It is a multifunctional enzyme that contains a NAD-dependent deacetylase activity that is specific for HISTONES and a mono-ADP-ribosyltransferase activity.. paclitaxel defined as following: A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.. lamellipodia defined as following: A thin sheetlike process extended by the leading edge of a migrating cell or extending cell process; contains a dense meshwork of actin filaments. [ISBN:0815316194]. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. histone deacetylase 6 defined as following: Deacetylases that remove N-acetyl groups from amino side chains of the amino acids of HISTONES. The enzyme family can be divided into at least three structurally-defined subclasses. Class I and class II deacetylases utilize a zinc-dependent mechanism. The sirtuin histone deacetylases belong to class III and are NAD-dependent enzymes.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. tumor cell lines defined as following: A cell line derived from cultured tumor cells.. GRK2 defined as following: Catalysis of the reaction: ATP + beta-adrenergic receptor = ADP + phospho-beta-adrenergic receptor. [EC:2.7.11.15, MetaCyc:BETA-ADRENERGIC-RECEPTOR-KINASE-RXN]. alpha-tubulin defined as following: Tubulin alpha-3C/D chain (450 aa, ~50 kDa) is encoded by the human TUBA3C gene. This protein is involved in microtubule structural dynamics.. tumor cells defined as following: Cells of, or derived from, a tumor.. endothelial defined as following: A layer of epithelium that lines the heart, blood vessels (ENDOTHELIUM, VASCULAR), lymph vessels (ENDOTHELIUM, LYMPHATIC), and the serous cavities of the body..", "label": "yes"} {"id": "converted_4169", "sentence1": "Has dupilumab been FDA approved for atopic dermatitis?", "sentence2": "Recent advances and understanding of the pathogenesis of AD have resulted in new therapies that target specific pathways with increased efficacy and the potential for less systemic side effects. New FDA-approved therapies for AD are crisaborole and dupilumab. , In March of 2017, the United States Food and Drug Administration (FDA) approved dupilumab for the treatment of moderate-to-severe atopic dermatitis in adults that is uncontrolled with topical medications, becoming the first biologic agent approved to treat this chronic skin condition., Dupilumab is the first US FDA approved biologic for treatment of atopic dermatitis., Dupilumab is the first biological treatment approved for moderate-to-severe atopic dermatitis (AD).[SEP]Relations: Dupilumab has relations: drug_drug with Tarextumab, drug_drug with Tarextumab, drug_drug with Dusigitumab, drug_drug with Dusigitumab, drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with IGN311, drug_drug with IGN311, drug_drug with Opicinumab, drug_drug with Opicinumab. Definitions: atopic dermatitis defined as following: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed).. Dupilumab defined as following: A recombinant human monoclonal immunoglobulin G4 (IgG4) antibody directed against the alpha chain of the interleukin-4 receptor (IL-4R alpha) with potential immunomodulatory activities. Upon injection, dupilumab selectively binds to the IL-4R alpha chain. This disrupts IL-4/IL-13 signaling and prevents the activation of downstream pathways that mediate type 2 inflammation and may potentially inhibit tumor cell proliferation, survival, and metastasis. IL-4 and IL-13 receptors are present on the surface of numerous cells involved in the pathophysiology of type-2 helper T-cell (Th2) allergic responses, including B-lymphocytes, eosinophils, dendritic cells (DCs), monocytes, macrophages, basophils, keratinocytes, bronchial epithelial cells, endothelial cells, fibroblasts, and airway smooth muscle cells. Additionally, both IL-4 and IL-13 receptors are overexpressed in a variety of cancers and IL-4 and IL-13 and may serve as biomarkers for cancer aggressiveness. IL-4 and IL-13 are thought to be key regulatory cytokines in the tumor microenvironment (TME) and may play a role in the activation of tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) that mediate tumor cell survival..", "label": "yes"} {"id": "converted_1519", "sentence1": "Does nifedipine inhibit L-type calcium channels?", "sentence2": "Nifedipine, an L-type calcium channel blocker, reduced the expression of synaptogamin and syntaxin and blocked the suppressive effect of vecuronium, suggesting that both agents inhibit presynaptic L-type calcium channels., Treatment with nifedipine to inhibit calcium influx via the L-type channel Cav1.2 (alpha(1C)) inhibited the TGFbeta stimulated increase in ANK expression at all phases of chondrogenesis., Finally, we found that PKCepsilon-induced stellation was significantly reduced by the specific L-type channel blocker nifedipine, indicating that calcium influx through VGCC mediates the change in astrocyte morphology induced by PKCepsilon., However, APV and nifedipine, an inhibitor of L-type calcium channels, failed to inhibit LTP when administered following the slow increase in ethanol., Both the metallic ions Cd2+ and Ni2+, known to inhibit voltage-gated calcium channels and T-type channels, respectively, and verapamil and nifedipine, typical blocker of L-type calcium channels completely prevented the hypoxic neuronal NO generation., Further, the L-type calcium channel blocker, nifedipine, was able to inhibit the initial increase in [Ca2+]i, suggesting that at least this phase of the TMT effect was mediated by calcium channels, although nifedipine had no significant effect on the time to reach the maximal [Ca2+]i level, Treatment with omega-conotoxin GVIA (3 microM) or nifedipine (10 microM) to inhibit Ca(2+) influx through N- or L-type voltage-dependent calcium channels (VDCCs), respectively, also decreased the rate of AP repolarization and increased AP duration, Concentrations of nifedipine (10 microM) and nimodipine (3 microM) that maximally inhibit L-type calcium channels reduced the sI(AHP) by 30 and 50%, respectively, Consequently, it was demonstrated in the present study that nimodipine and nitrendipine inhibit both L- and N-type calcium channels and thus seem to be unique among the dihydropyridines examined in their effects on calcium channels in dibutyryl cAMP-differentiated neuroblastoma x glioma hybrid NG 108-15 cells, whereas nifedipine and niguldipine appear to block mainly L-type calcium channels, However, APV and nifedipine, an inhibitor of L-type calcium channels, failed to inhibit LTP when administered following the slow increase in ethanol, Calcium-channel antagonists, omega-conotoxin GVIA (omega-CgTx GVIA; N-type), nifedipine (L-type), and omega-conotoxin MVIIC (omega-CmTx MVIIC; P/Q type), were used to characterize the voltage-operated Ca(2+) channels (VOCCs) involved in this release, The T- and L-type calcium channel blocker (CCB) mibefradil attenuates leg edema induced by the L-type CCB nifedipine in the spontaneously hypertensive rat: a novel differentiating assay., L-type calcium channel antagonist nifedipine reduces neurofilament restitution following traumatic optic nerve injury., Nifedipine, an L-type calcium channel blocker, restores the hypnotic response in rats made tolerant to the alpha-2 adrenergic agonist dexmedetomidine., Comparison of L-type calcium channel blockade by nifedipine and/or cadmium in guinea pig ventricular myocytes., Nifedipine inhibits picrotoxin-induced seizure activity: further evidence on the involvement of L-type calcium channel blockers in epilepsy.[SEP]Relations: Nifedipine has relations: drug_drug with Calcium, drug_drug with Calcium, drug_drug with Calcium chloride, drug_drug with Calcium chloride, drug_drug with Calcium cation, drug_drug with Calcium cation, drug_drug with Calcium levulinate, drug_drug with Calcium levulinate, drug_drug with Calcium acetate, drug_drug with Calcium acetate. Definitions: omega-conotoxin GVIA defined as following: A neurotoxic peptide, which is a cleavage product (VIa) of the omega-Conotoxin precursor protein contained in venom from the marine snail, CONUS geographus. It is an antagonist of CALCIUM CHANNELS, N-TYPE.. cadmium defined as following: An element with atomic symbol Cd, atomic number 48, and atomic weight 112.41. It is a metal and ingestion will lead to CADMIUM POISONING.. dihydropyridines defined as following: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position.. L-type calcium channel defined as following: Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and non-excitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.. epilepsy defined as following: A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313). ethanol defined as following: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.. LTP defined as following: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory.. nifedipine defined as following: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.. dexmedetomidine defined as following: An imidazole derivate and active d-isomer of medetomidine with analgesic, anxiolytic and sedative properties. Dexmedetomidine selectively binds to presynaptic alpha-2 adrenoceptors located in the brain, thereby inhibiting the release of norepinephrine from synaptic vesicles. This leads to an inhibition of postsynaptic activation of adrenoceptors, which inhibit sympathetic activity, thereby leading to sedation and anxiolysis. The analgesic effect of this agent is mediated by binding to alpha-2 adrenoceptors in the spinal cord.. syntaxin defined as following: A subfamily of Q-SNARE PROTEINS which occupy the same position as syntaxin 1A in the SNARE complex and which also are most similar to syntaxin 1A in their AMINO ACID SEQUENCE. This subfamily is also known as the syntaxins, although a few so called syntaxins are Qc-SNARES.. nitrendipine defined as following: A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive.. verapamil defined as following: A calcium channel blocker that is a class IV anti-arrhythmia agent.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. APV defined as following: A synthetic derivative of hydroxyethylamine sulfonamide that selectively binds to and inhibits human immunodeficiency virus (HIV) protease.. vecuronium defined as following: A synthetic, intermediate-acting mono-quaternary steroid and non-depolarizing neuromuscular blocking agent, with muscle relaxant activity. Vecuronium competitively binds to and blocks the nicotinic acetylcholine receptor at the neuromuscular junction, thereby preventing acetylcholine (ACh) binding and resulting in skeletal muscle relaxation and paralysis. Vecuronium has a shorter duration of action than pancuronium.. mibefradil defined as following: A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE.. traumatic optic nerve injury defined as following: Injuries to the optic nerve induced by a trauma to the face or head. These may occur with closed or penetrating injuries. Relatively minor compression of the superior aspect of orbit may also result in trauma to the optic nerve. Clinical manifestations may include visual loss, PAPILLEDEMA, and an afferent pupillary defect.. astrocyte defined as following: A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from \"star\" cells) are irregularly shaped with many long processes, including those with \"end feet\" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and \"reactive astrocytes\" (along with MICROGLIA) respond to injury.. nimodipine defined as following: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.. guinea pig defined as following: The domesticated guinea pig, Cavia porcellus.. neuroblastoma defined as following: A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51). ANK defined as following: Human ANK1 wild-type allele is located in the vicinity of 8p11.1 and is approximately 243 kb in length. This allele, which encodes ankyrin-1 protein, plays a role in erythrocyte morphology. Mutation of the gene is associated with spherocytosis.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. TMT defined as following: The subject's ability to connect 25 numbered and lettered circles in sequence in a specific length of time. A score of 12 or below is suggestive of organic brain damage..", "label": "yes"} {"id": "converted_160", "sentence1": "Is there any software for automated analysis of FISH images?", "sentence2": "he study demonstrated the feasibility of automated FISH signal analysis that applying a CAD scheme to the automated generated 2-D projection images., A color imaging technique, multiplex fluorescent in situ hybridization (M-FISH), has been developed to ease the analysis of the process. Using an M-FISH technique each chromosome class (1,2, …,22,X,Y) is stained with a unique color. However, significant variations between images are observed due to a number of factors such as uneven hybridization and spectral overlap among channels. These types of variations influence the pixel classification accuracy of image classification methods which are supervised and require a set of annotated images for training. In this paper, we present a fully unsupervised M-FISH chromosome image classification methodology. Our main contributions are 1) the assumption that the intensity of a chromosome pixel is sampled from multiple Gaussian components [Gaussian mixture model (GMM)] such that each component corresponds to one chromosome class, and 2) the initialization of the GMM model using the emission information of each chromosome class. This is feasible since prior to the M-FISH image acquirement, we already know which chromosome class is emitting to each of the five M-FISH image channels. The method has been tested on a large number of M-FISH images and an overall accuracy of 89.85% is reported. Our method is unsupervised and presents higher classification accuracy even when it is compared with common supervised based methods., hybridization (FISH) tests provide promising molecular imaging biomarkers to more accurately and reliably detect and diagnose cancers and genetic disorders. Since current manual FISH signal analysis is low-efficient and inconsistent, which limits its clinical utility, developing automated FISH image scanning systems and computer-aided detection (CAD) schemes has been attracting research interests. To acquire high-resolution FISH images in a multi-spectral scanning mode, a huge amount of image data with the stack of the multiple three-dimensional (3-D) image slices is generated from a single specimen. Automated preprocessing these scanned images to eliminate the non-useful and redundant data is important to make the automated FISH tests acceptable in clinical applications. In this study, a dual-detector fluorescence image scanning system was applied to scan four specimen slides with FISH-probed chromosome X. A CAD scheme was developed to detect analyzable interphase cells and map the multiple imaging slices recorded FISH-probed signals into the 2-D projection images. CAD scheme was then applied to each projection image to detect analyzable interphase cells using an adaptive multiple-threshold algorithm, identify FISH-probed signals using a top-hat transform, and compute the ratios between the normal and abnormal cells. To assess CAD performance, the FISH-probed signals were also independently visually detected by an observer. The Kappa coefficients for agreement between CAD and observer ranged from 0.69 to 1.0 in detecting/counting FISH signal spots in four testing samples., In this paper we developed a sparse representation-based classification (SRC) algorithm based on L1-norm minimization for classifying chromosomes from multicolor fluorescence in situ hybridization (M-FISH) images. The algorithm has been tested on a comprehensive M-FISH database that we established, demonstrating improved performance in classification. When compared with other pixel-wise M-FISH image classifiers such as fuzzy c-means (FCM) clustering algorithms and adaptive fuzzy c-means (AFCM) clustering algorithms that we proposed earlier the current method gave the lowest classification error. In order to evaluate the performance of different SRC for M-FISH imaging analysis, three different sparse representation methods, namely, Homotopy method, Orthogonal Matching Pursuit (OMP), and Least Angle Regression (LARS), were tested and compared. Results from our statistical analysis have shown that Homotopy based method is significantly better than the other two methods. , Fluorescence in situ hybridization (FISH) is used to study the organization and the positioning of specific DNA sequences within the cell nucleus. Analyzing the data from FISH images is a tedious process that invokes an element of subjectivity. Automated FISH image analysis offers savings in time as well as gaining the benefit of objective data analysis. While several FISH image analysis software tools have been developed, they often use a threshold-based segmentation algorithm for nucleus segmentation. As fluorescence signal intensities can vary significantly from experiment to experiment, from cell to cell, and within a cell, threshold-based segmentation is inflexible and often insufficient for automatic image analysis, leading to additional manual segmentation and potential subjective bias. To overcome these problems, we developed a graphical software tool called FISH Finder to automatically analyze FISH images that vary significantly. By posing the nucleus segmentation as a classification problem, compound Bayesian classifier is employed so that contextual information is utilized, resulting in reliable classification and boundary extraction. This makes it possible to analyze FISH images efficiently and objectively without adjustment of input parameters. Additionally, FISH Finder was designed to analyze the distances between differentially stained FISH probes., The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining. Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell. METHODS: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion. RESULTS: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217., The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining.Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell. METHODS: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion. RESULTS: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217. There was no significant difference between CD133 positive tumour and CD133 negative tumour cells. , The simultaneous detection of protein expression and gene copy number changes in patient samples, like paraffin-embedded tissue sections, is challenging since the procedures of immunohistochemistry (IHC) and Fluorescence in situ Hybridization (FISH) negatively influence each other which often results in suboptimal staining.Therefore, we developed a novel automated algorithm based on relocation which allows subsequent detection of protein content and gene copy number changes within the same cell.Methods: Paraffin-embedded tissue sections of colorectal cancers were stained for CD133 expression. IHC images were acquired and image coordinates recorded. Slides were subsequently hybridized with fluorescently labeled DNA probes. FISH images were taken at the previously recorded positions allowing for direct comparison of protein expression and gene copy number signals within the same cells/tissue areas. Relocation, acquisition of the IHC and FISH images, and enumeration of FISH signals in the immunophenotyped tumour areas were done in an automated fashion.Results: Automated FISH analysis was performed on 13 different colon cancer samples that had been stained for CD133; each sample was scored for MYC, ZNF217 and Chromosome 6 in CD133 positive and negative glands. From the 13 cases four (31%) showed amplification for the MYC oncogene and seven of 13 (54%) cases were amplified for ZNF217. There was no significant difference between CD133 positive tumour and CD133 negative tumour cells.[SEP]Relations: colorectal carcinoma has relations: disease_protein with JPH3, disease_protein with JPH3, disease_protein with QKI, disease_protein with QKI, disease_protein with EFS, disease_protein with EFS, disease_protein with NRCAM, disease_protein with NRCAM, disease_protein with AURKA, disease_protein with AURKA. Definitions: cell nucleus defined as following: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). CD133 defined as following: Prominin-1 (865 aa, ~97 kDa) is encoded by the human PROM1 gene. This protein may play a role in hematopoiesis, but an exact function has yet to be elucidated. The protein has been implicated in tumor pathogenesis and formation in several cancers, including retinoblastoma, hemangioma, and glioblastoma phenotypes. Additionally, the protein has been used as a marker to distinguish cells that have the potential to become cancerous from the larger normal cell population.. SRC defined as following: Proto-oncogene tyrosine-protein kinase Src (536 aa, ~60 kDa) is encoded by the human SRC gene. This protein is involved in both receptor-mediated signal transduction and tyrosine phosphorylation.. DNA sequences defined as following: The sequence of nucleotide residues along a DNA chain.. chromosomes defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.. colorectal cancers defined as following: A malignant epithelial neoplasm that arises from the colon or rectum and invades through the muscularis mucosa into the submucosa. The vast majority are adenocarcinomas.. MYC defined as following: Myc proto-oncogene protein (439 aa, ~49 kDa) is encoded by the human MYC gene. This protein plays a role in the regulation of transcription and cell proliferation.. ZNF217 defined as following: Zinc finger protein 217 (1048 aa, ~115 kDa) is encoded by the human ZNF217 gene. This protein plays a role in the negative regulation of transcription.. DNA probes defined as following: Species- or subspecies-specific DNA (including COMPLEMENTARY DNA; conserved genes, whole chromosomes, or whole genomes) used in hybridization studies in order to identify microorganisms, to measure DNA-DNA homologies, to group subspecies, etc. The DNA probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the DNA probe include the radioisotope labels 32P and 125I and the chemical label biotin. The use of DNA probes provides a specific, sensitive, rapid, and inexpensive replacement for cell culture techniques for diagnosing infections.. colon cancer defined as following: A primary or metastatic malignant neoplasm that affects the colon. Representative examples include carcinoma, lymphoma, and sarcoma.. Chromosome 6 defined as following: A specific pair GROUP C CHROMSOMES of the human chromosome classification.. abnormal cells defined as following: An abnormal human cell type which can occur in either disease states or disease models.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. MYC oncogene defined as following: A viral and cellular gene. A proto-oncogene, identified in several avian tumors, encoding a nuclear protein with a leucine zipper motif..", "label": "yes"} {"id": "converted_34", "sentence1": "Do mutations of AKT1 occur in meningiomas?", "sentence2": "The recent identification of somatic mutations in components of the SHH-GLI1 and AKT1-MTOR signaling pathways indicates the potential for cross talk of these pathways in the development of meningiomas., A mutation in PIK3CA or AKT1 was found in around 9 % of the cases., AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry., AKT1E17K mutations were exclusively seen in meningiomas and occurred in 65 of 958 of these tumors. A strong preponderance was seen in the variant of meningothelial meningioma WHO grade I of basal and spinal localization. In contrast, AKT1E17K mutations were rare in WHO grade II and absent in WHO grade III meningiomas. , We observed strong up-regulation of SFRP1 expression in all meningiomas with AKT1E17K mutation and in HEK293 cells after transfection with mutant AKT1E17K, but not in meningiomas and HEK293 cells lacking this mutation., SMO and AKT1 mutations occur in non-NF2 meningiomas., Recurrent mutations in SMO and AKT1 are mutually exclusive with NF2 loss in meningioma., Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations., A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways., Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO., A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways., SMO and AKT1 mutations occur in non-NF2 meningiomas, The recent identification of somatic mutations in components of the SHH-GLI1 and AKT1-MTOR signaling pathways indicates the potential for cross talk of these pathways in the development of meningiomas, A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways, Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO, Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations, Recurrent mutations in SMO and AKT1 are mutually exclusive with NF2 loss in meningioma, A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. , A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. [SEP]Relations: benign meningioma has relations: disease_protein with AKT1, disease_protein with AKT1, disease_protein with HES1, disease_protein with HES1, disease_protein with BAP1, disease_protein with BAP1. meningothelial meningioma has relations: disease_protein with AKT1, disease_protein with AKT1, disease_protein with HES1, disease_protein with HES1. Definitions: PIK3CA defined as following: This gene is involved in apoptosis, cell growth and angiogenesis.. HEK293 cells defined as following: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.. meningiomas defined as following: A relatively common neoplasm of the CENTRAL NERVOUS SYSTEM that arises from arachnoidal cells. The majority are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Meningiomas have a predilection to arise from the parasagittal region, cerebral convexity, sphenoidal ridge, olfactory groove, and SPINAL CANAL. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2056-7). TRAF7 defined as following: This gene is involved in both MAPK signaling and protein ubiquitination.. variant defined as following: An alteration or difference from a norm or standard.. KLF4 defined as following: Krueppel-like factor 4 (470 aa, ~50 kDa) is encoded by the human KLF4 gene. This protein regulates transcription.. AKT1 defined as following: RAC-alpha serine/threonine-protein kinase (480 aa, ~56 kDa) is encoded by the human AKT1 gene. This protein is involved in signal transduction, serine/threonine phosphorylation, apoptosis regulation and neurogenesis.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. meningothelial meningioma defined as following: A WHO grade I meningioma characterized by the presence of tumor cells that form lobules. The tumor cells are generally uniform. Whorls and psammoma bodies are usually not present.. SFRP1 defined as following: This gene is involved in signaling.. SMO defined as following: An Austronesian language spoken mainly in the Samoan islands.. meningioma defined as following: A grade I, slowly growing meningioma. Only a minority of tumors recur following complete resection.. NF2 defined as following: An autosomal dominant disorder characterized by a high incidence of bilateral acoustic neuromas as well as schwannomas (NEURILEMMOMA) of other cranial and peripheral nerves, and other benign intracranial tumors including meningiomas, ependymomas, spinal neurofibromas, and gliomas. The disease has been linked to mutations of the NF2 gene (GENES, NEUROFIBROMATOSIS 2) on chromosome 22 (22q12) and usually presents clinically in the first or second decade of life.. mutant defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. skull base defined as following: The inferior region of the skull consisting of an internal (cerebral), and an external (basilar) surface.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"} {"id": "converted_3655", "sentence1": "Does gavestinel improve outcomes of stroke patients?", "sentence2": "CONCLUSION: Consistent with the clinical outcomes in the GAIN trials, no effects of gavestinel on ischemic infarction was observed., No effects of gavestinel on infarct volume were observed in the primary or other analyses. , Gavestinel does not improve outcome after acute intracerebral hemorrhage: an analysis from the GAIN International and GAIN Americas studies., Both trials reported that gavestinel was ineffective in ischemic stroke. , CONCLUSIONS: These observations from the combined GAIN International and GAIN Americas trials suggest that gavestinel is not of substantial benefit or harm to patients with primary intracerebral hemorrhage. , Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists such as Selfotel, Aptiganel, Gavestinel and others failed to show neuroprotective efficacy in human clinical trials or produced intolerable central nervous system adverse effects., METHODS: We studied all patients of the Glycine Antagonist (gavestinel) In Neuroprotection (GAIN) International Trial with ischemic stroke alive at day 7, excluding patients with hemorrhagic events and deaths from nonstroke-related causes. The GAIN International Trial was a randomized, double-blind, placebo-controlled, and parallel-group trial; because the study drug had no effect on stroke outcome, treatment groups were combined for this analysis. , Gavestinel produces no benefit for stroke patients, study finds., The wonder drug, gavestinel, failed to produce any significant treatment benefits for patients treated within six hours after experiencing an acute ischemic stroke, according to the recent results of a major clinical trial of the neuroprotectant. , INTERPRETATION: Treatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome., INTERPRETATION\n\nTreatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome., CONCLUSION\n\nIn this study, gavestinel administered up to 6 hours after an acute ischemic stroke did not improve functional outcome at 3 months., Both trials reported that gavestinel was ineffective in ischemic stroke., INTERPRETATION Treatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome., Both trials reported that gavestinel was ineffective in ischemic stroke., Gavestinel produces no benefit for stroke patients , study finds ., The wonder drug, gavestinel, failed to produce any significant treatment benefits for patients treated within six hours after experiencing an acute ischemic stroke, according to the recent results of a major clinical trial of the neuroprotectant., The wonder drug, gavestinel, failed to produce any significant treatment benefits for patients treated within six hours after experiencing an acute ischemic stroke, according to the recent results of a major clinical trial of the neuroprotectant., Treatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome., In this study, gavestinel administered up to 6 hours after an acute ischemic stroke did not improve functional outcome at 3 months.[SEP]Relations: Gavestinel has relations: drug_drug with Rifampicin, drug_drug with Rifampicin, drug_drug with Enasidenib, drug_drug with Enasidenib, drug_drug with Silibinin, drug_drug with Silibinin, drug_drug with Indinavir, drug_drug with Indinavir, drug_drug with Pazopanib, drug_drug with Pazopanib. Definitions: drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. deaths defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. human defined as following: Members of the species Homo sapiens.. ischemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue.. stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810).", "label": "no"} {"id": "converted_1491", "sentence1": "Is there any research that relates the function of Notch Signaling with Alzheimer Disease?", "sentence2": "RIP regulates signaling pathways by abrogating or releasing signaling molecules. Since the discovery, already >15 years ago, of its catalytic component, presenilin, and even much earlier with the identification of amyloid precursor protein as its first substrate, γ-secretase has been commonly associated with Alzheimer's disease. However, starting with Notch and thereafter a continuously increasing number of novel substrates, γ-secretase is becoming linked to an equally broader range of biological processes., In the last decade, increasing evidence has pointed out an important role of this pathway beyond embryonic development, indicating that Notch also displays a critical function in the mature brain of vertebrates and invertebrates. This pathway appears to be involved in neural progenitor regulation, neuronal connectivity, synaptic plasticity and learning/memory. In addition, Notch appears to be aberrantly regulated in neurodegenerative diseases, including Alzheimer's disease and ischemic injury, Along with β-secretase, this enzyme produces the amyloid β-protein of Alzheimer's disease (AD) from the amyloid β-protein precursor. Because of its key role in the pathogenesis of AD, γ-secretase has been a prime target for drug discovery, and many inhibitors of this protease have been developed. The therapeutic potential of these inhibitors is virtually negated by the fact that γ-secretase is an essential part of the Notch signaling pathway, rendering the compounds unacceptably toxic upon chronic exposure, High physiological concentrations of Aβ monomer induced angiogenesis by a conserved mechanism that blocks γ-secretase processing of a Notch intermediate, NEXT, and reduces the expression of downstream Notch target genes. Our findings allude to an integration of signaling pathways that utilize γ-secretase activity, which may have significant implications for our understanding of Alzheimer's pathogenesis vis-à-vis vascular changes that set the stage for ensuing neurodegeneration., Aggregated forms of Aβ have a pathogenic role in Alzheimer disease and, thus, reducing the Aβ levels by inhibiting γ-secretase is a possible treatment strategy for Alzheimer disease. Regrettably, clinical trials have shown that inhibition of γ-secretase results in Notch-related side effects. Therefore, it is of great importance to find ways to inhibit amyloid precursor protein (APP) processing without disturbing vital signaling pathways such as Notch. Nicastrin (Nct) is part of the γ-secretase complex and has been proposed to be involved in substrate recognition and selection[SEP]Relations: Alzheimer disease has relations: disease_disease with genetic dementia, disease_disease with genetic dementia, disease_disease with dementia (disease), disease_disease with dementia (disease), disease_protein with GAPDHS, disease_protein with GAPDHS, disease_disease with familial Alzheimer disease, disease_disease with familial Alzheimer disease, disease_protein with ARC, disease_protein with ARC. Definitions: amyloid precursor protein defined as following: A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.. RIP defined as following: This gene is involved in the regulation of small GTPase activity.. neurodegeneration defined as following: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.. APP defined as following: An application designed specifically for use on a smartphone.. Nicastrin defined as following: This gene is involved in the regulation of gamma-secretase activity.. presenilin defined as following: Integral membrane protein of Golgi and endoplasmic reticulum. Its homodimer is an essential component of the gamma-secretase complex that catalyzes the cleavage of membrane proteins such as NOTCH RECEPTORS and AMYLOID BETA-PEPTIDES precursors. PSEN1 mutations cause early-onset ALZHEIMER DISEASE type 3 that may occur as early as 30 years of age in humans.. neurodegenerative diseases defined as following: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.. toxic defined as following: The finding of bodily harm due to the poisonous effects of something.. protease defined as following: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. vertebrates defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes..", "label": "yes"} {"id": "converted_2072", "sentence1": "Is vemurafenib used for thyroid cancer?", "sentence2": "Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial., Vemurafenib, an oncogenic BRAF kinase inhibitor approved for BRAF-positive melanoma, showed clinical benefit in three patients with BRAF(V600E)-positive papillary thyroid cancer in a phase 1 trial., INTERPRETATION: Vemurafenib showed antitumour activity in patients with progressive, BRAF(V600E)-positive papillary thyroid cancer refractory to radioactive iodine who had never been treated with a multikinase inhibitor. , CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation., Efficacy and tolerability of vemurafenib in patients with BRAF(V600E) -positive papillary thyroid cancer: M.D. Anderson Cancer Center off label experience., CONCLUSIONS: Vemurafenib is a potentially effective and well-tolerated treatment strategy in patients with advanced PTC harboring the BRAF(V600E) mutation., The US Food and Drug Administration-approved BRAF inhibitors, vemurafenib and dabrafenib, have demonstrated superior efficacy in patients with BRAF-mutant melanomas but have limited efficacy in BRAF-mutant colorectal cancer. Little is known at this time regarding BRAF inhibitors in thyroid cancer. Initial reports in patients with progressive, radioactive iodine-refractory BRAF-mutant papillary thyroid cancer suggest response rates of approximately 30-40%., Use of vemurafenib in anaplastic thyroid carcinoma: a case report., Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib., CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.DESIGN: A retrospective review at MD Anderson Cancer Center.METHODS: The best responses were evaluated using RECIST v1.1., Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.A retrospective review at MD Anderson Cancer Center.The best responses were evaluated using RECIST v1.1, CONTEXT: Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.OBJECTIVE: To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.DESIGN: A retrospective review at MD Anderson Cancer Center.METHODS: The best responses were evaluated using RECIST v1.1. , Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib., Metformin or rapamycin adjuvant treatment may provide clinical benefits with minimal side effects to BRAFV600E-positive advanced thyroid cancer patients treated with vemurafenib., Vemurafenib, a selective BRAF inhibitor, appears to have promising clinical activity in patients with papillary thyroid cancer (PTC) harboring the BRAF(V600E) mutation.To determine the efficacy and safety of vemurafenib when used outside of a clinical trial.A retrospective review at MD Anderson Cancer Center.The best responses were evaluated using RECIST v1.1., Our data demonstrate that vemurafenib induces ER stress response-mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib.., Combination of vemurafenib and metformin decreased cell viability and increased apoptosis in both BCPAP papillary thyroid cancer cells and 8505c anaplastic thyroid cancer cells., Targeting autophagy sensitizes BRAF-mutant thyroid cancer to vemurafenib., Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib., mTOR inhibitors sensitize thyroid cancer cells to cytotoxic effect of vemurafenib., Vemurafenib induced a high level of autophagy in BRAF-mutant thyroid cancer cells.[SEP]Relations: Vemurafenib has relations: drug_drug with Parathyroid hormone, drug_drug with Parathyroid hormone, contraindication with iris disease, contraindication with iris disease, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Thyroid, porcine, drug_drug with Thyroid, porcine, drug_drug with Testosterone, drug_drug with Testosterone. Definitions: metformin defined as following: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289). Vemurafenib defined as following: An orally bioavailable, ATP-competitive, small-molecule inhibitor of BRAF(V600E) kinase with potential antineoplastic activity. Vemurafenib selectively binds to the ATP-binding site of BRAF(V600E) kinase and inhibits its activity, which may result in an inhibition of an over-activated MAPK signaling pathway downstream in BRAF(V600E) kinase-expressing tumor cells and a reduction in tumor cell proliferation. Approximately 90% of BRAF gene mutations involve a valine-to-glutamic acid mutation at residue 600 (V600E); the oncogene protein product, BRAF(V600E) kinase, exhibits a markedly elevated activity that over-activates the MAPK signaling pathway. The BRAF(V600E) gene mutation has been found to occur in approximately 60% of melanomas, and in about 8% of all solid tumors, including melanoma, colorectal, thyroid and other cancers.. iodine defined as following: homeopathic drug. thyroid cancer defined as following: A primary or metastatic malignant neoplasm affecting the thyroid gland.. ER defined as following: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed). Propranolol defined as following: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.. papillary thyroid cancer defined as following: A differentiated adenocarcinoma arising from the follicular cells of the thyroid gland. Radiation exposure is a risk factor and it is the most common malignant thyroid lesion, comprising 75% to 80% of all thyroid cancers in iodine sufficient countries. Diagnostic procedures include thyroid ultrasound and fine needle biopsy. Microscopically, the diagnosis is based on the distinct characteristics of the malignant cells, which include enlargement, oval shape, elongation, and overlapping of the nuclei. The nuclei also display clearing or have a ground glass appearance.. RECIST defined as following: Standard parameters to be used when documenting response of solid tumors to treatment; a set of published rules that define when cancer patients improve (\"respond\"), stay the same (\"stable\"), or worsen (\"progression\") during treatments. (from www.recist.com). PTC defined as following: The evaluation of the liver and biliary tree using a contrast agent injected directly into the liver.. anaplastic thyroid carcinoma defined as following: An aggressive THYROID GLAND malignancy which generally occurs in IODINE-deficient areas in people with previous thyroid pathology such as GOITER. It is associated with CELL DEDIFFERENTIATION of THYROID CARCINOMA (e.g., FOLLICULAR THYROID CARCINOMA; PAPILLARY THYROID CANCER). Typical initial presentation is a rapidly growing neck mass which upon metastasis is associated with DYSPHAGIA; NECK PAIN; bone pain; DYSPNEA; and NEUROLOGIC DEFICITS.. dabrafenib defined as following: An orally bioavailable inhibitor of B-raf (BRAF) protein with potential antineoplastic activity. Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. B-raf belongs to the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations.. rapamycin defined as following: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. BRAF defined as following: Serine/threonine-protein kinase B-raf (766 aa, ~84 kDa) is encoded by the human BRAF gene. This protein plays a role in protein phosphorylation, mitogenesis and neuronal signal transduction.. vemurafenib defined as following: An orally bioavailable, ATP-competitive, small-molecule inhibitor of BRAF(V600E) kinase with potential antineoplastic activity. Vemurafenib selectively binds to the ATP-binding site of BRAF(V600E) kinase and inhibits its activity, which may result in an inhibition of an over-activated MAPK signaling pathway downstream in BRAF(V600E) kinase-expressing tumor cells and a reduction in tumor cell proliferation. Approximately 90% of BRAF gene mutations involve a valine-to-glutamic acid mutation at residue 600 (V600E); the oncogene protein product, BRAF(V600E) kinase, exhibits a markedly elevated activity that over-activates the MAPK signaling pathway. The BRAF(V600E) gene mutation has been found to occur in approximately 60% of melanomas, and in about 8% of all solid tumors, including melanoma, colorectal, thyroid and other cancers..", "label": "yes"} {"id": "converted_2227", "sentence1": "Is Downs syndrome associated with decreased risk of leukemia?", "sentence2": "The association of Down's syndrome and leukemia has been documented for over 50 years. Multiple studies have established the incidence of leukemia in Down's syndrome patients to be 10- to 20-fold higher than that in the general population., We present a case of congenital acute myeloid leukemia manifesting from the very first day of birth. Diagnosis of acute myeloid leukemia was suspected by the presence of blasts in the peripheral blood smear and was confirmed on bone marrow by flowcytometry. Karyotyping revealed Trisomy 21., Juvenile myelomonocytic leukemia (JMML) and a solitary cases of acute myeloid leukemia (AML) in Downs syndrome. , This was thus confirmed to be a case with transient leukemia with Downs syndrome.[SEP]Relations: Down syndrome has relations: disease_phenotype_positive with Decreased fertility, disease_phenotype_positive with Decreased fertility, disease_phenotype_positive with Acute megakaryocytic leukemia, disease_phenotype_positive with Acute megakaryocytic leukemia, disease_phenotype_positive with Sporadic, disease_phenotype_positive with Sporadic, disease_phenotype_positive with Short palm, disease_phenotype_positive with Short palm, disease_phenotype_positive with Short neck, disease_phenotype_positive with Short neck. Definitions: JMML defined as following: A leukemia affecting young children characterized by SPLENOMEGALY, enlarged lymph nodes, rashes, and hemorrhages. Traditionally classed as a myeloproliferative disease, it is now considered a mixed myeloproliferative-mylelodysplastic disorder.. acute myeloid leukemia defined as following: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.. leukemia defined as following: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006). Downs syndrome defined as following: A chromosome disorder associated either with an extra CHROMOSOME 21 or an effective TRISOMY for chromosome 21. Clinical manifestations include HYPOTONIA, short stature, BRACHYCEPHALY, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, single transverse palmar crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213).", "label": "no"} {"id": "converted_1662", "sentence1": "Are Notch mutations related to T-cell Acute Lymphoblastic Leukemia (T-ALL)?", "sentence2": "Notch receptors participate in a highly conserved signalling pathway that regulates normal development and tissue homeostasis in a context- and dose-dependent manner. Deregulated Notch signalling has been implicated in many diseases, but the clearest example of a pathogenic role is found in T-cell lymphoblastic leukaemia/lymphoma (T-LL), in which the majority of human and murine tumours have acquired mutations that lead to aberrant increases in Notch1 signalling., NOTCH proteins (NOTCH1, NOTCH2, NOTCH3 and NOTCH4) play crucial roles in embryonic development. Also, mounting evidence indicates that NOTCH contributes to the pathogenesis of hematopoietic and solid malignancies. Recent studies reported a high incidence of gain-of-function mutations of the NOTCH1 gene in T-cell acute lymphoblastic leukemias (ALL). , Our data indicate that NOTCH1 is mutated in T-ALL, but not in other common human cancers, and that NOTCH2, NOTCH3 and NOTH4 genes are rarely mutated in common human cancers. , The Notch signaling pathway plays a critical role in maintaining the balance between cell proliferation, differentiation and apoptosis, and is a highly conserved signaling pathway that regulates normal development in a context- and dose-dependent manner. Dysregulation of Notch signaling has been suggested to be key events in a variety of hematological malignancies. Notch1 signaling appears to be the central oncogenic trigger in T cell acute lymphoblastic leukemia (T-ALL), in which the majority of human malignancies have acquired mutations that lead to constitutive activation of Notch1 signaling., T-cell acute lymphoblastic leukemia (T-ALL) is characterized as a high-risk stratified disease associated with frequent relapse, chemotherapy resistance, and a poorer prognostic outlook than B-precursor ALL. Many of the challenges in treating T-ALL reflect the lack of prognostic cytogenetic or molecular abnormalities on which to base therapy, including targeted therapy. Notch1 activating mutations were identified in more than 50% of T-ALL cases and can be therapeutically targeted with γ-secretase inhibitors (GSIs). , Notch1 is a transmembrane receptor that is frequently mutated in human T-cell acute lymphoblastic leukemia (T-ALL). , T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by aberrant activation of NOTCH1 in over 60% of T-ALL cases. The high prevalence of activating NOTCH1 mutations highlights the critical role of NOTCH signaling in the pathogenesis of this disease and has prompted the development of therapeutic approaches targeting the NOTCH signaling pathway. , Activating mutations in NOTCH1, an essential regulator of T cell development, are frequently found in human T cell acute lymphoblastic leukemia (T-ALL). , NOTCH signaling pathway is essential in T-cell development and NOTCH1 mutations are frequently present in T-cell acute lymphoblastic leukemia (T-ALL)., Activating Notch-1 mutations are frequent in T-cell acute lymphoblastic leukemia (T-ALL), occurring in >50% of patients., Mutations in NOTCH1/FBXW7 activate NOTCH signaling and are of prognostic significance in patients with T-cell acute lymphoblastic leukemia (T-ALL)., Gain-of-function mutations in Notch-1 have been reported in more than 50% of human T-cell acute lymphoblastic leukemia (T-ALL)., Notch signaling is of crucial importance in normal T-cell development and Notch 1 is frequently mutated in T-cell acute lymphoblastic leukemias (T-ALL), leading to aberrantly high Notch signaling., Activation of the Notch pathway occurs commonly in T acute lymphoblastic leukemia (T-ALL) because of mutations in Notch1 or Fbw7 and is involved in the regulation of cell proliferation and survival., T-cell acute lymphoblastic leukemia (T-ALL) patients frequently display NOTCH1 activating mutations and Notch can transcriptionally down-regulate the tumor suppressor PTEN., The identification of activating mutations in NOTCH1 in over 50% of T-cell acute lymphoblastic leukemias (T-ALL) has generated major interest in the elucidation of the mechanisms of transformation downstream of oncogenic NOTCH and in the targeting of the NOTCH signaling pathway in this disease., BACKGROUND: In T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), activating mutations of NOTCH1 are observed in more than 50% of cases, whereas the t(7;9)(q34;q34) involving NOTCH1 at 9q34 and TRB@ at 7q34 is an extremely rare but recurrent translocation., Activating mutations in NOTCH1 consitute the most prominent genetic abnormality in T-cell acute lymphoblastic leukemia (T-ALL)., T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that is frequently associated with activating mutations in NOTCH1 and dysregulation of MYC, The Notch signaling pathway has been recognized as a key factor for the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL), because of the high incidence of activating mutations of Notch1, Notch signaling is of crucial importance in normal T-cell development and Notch 1 is frequently mutated in T-cell acute lymphoblastic leukemias (T-ALL), leading to aberrantly high Notch signaling, NOTCH signaling pathway is essential in T-cell development and NOTCH1 mutations are frequently present in T-cell acute lymphoblastic leukemia (T-ALL), Activating Notch-1 mutations are frequent in T-cell acute lymphoblastic leukemia (T-ALL), occurring in >50% of patients, Gain-of-function mutations in Notch-1 have been reported in more than 50% of human T-cell acute lymphoblastic leukemia (T-ALL)[SEP]Relations: NOTCH1 has relations: disease_protein with precursor T-cell acute lymphoblastic leukemia, disease_protein with precursor T-cell acute lymphoblastic leukemia, disease_protein with acute lymphoblastic leukemia, disease_protein with acute lymphoblastic leukemia, disease_protein with acute lymphoblastic/lymphocytic leukemia, disease_protein with acute lymphoblastic/lymphocytic leukemia, disease_protein with acute lymphoblastic leukemia (disease), disease_protein with acute lymphoblastic leukemia (disease). NOTCH2 has relations: disease_protein with acute lymphoblastic leukemia (disease), disease_protein with acute lymphoblastic leukemia (disease). Definitions: Fbw7 defined as following: Human FBXW7 wild-type allele is located in the vicinity of 4q31.3 and is approximately 91 kb in length. This allele, which encodes F-box/WD-repeat protein 7, is involved in ubiquitin-dependent protein degradation and has been implicated in the maintenance of genomic integrity.. T-cell acute lymphoblastic leukemias defined as following: A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.. Notch1 defined as following: Human NOTCH1 wild-type allele is located in the vicinity of 9q34.3 and is approximately 51 kb in length. This allele, which encodes neurogenic locus notch homolog protein 1 protein, plays a role in developmental processes by controlling cell fate decisions.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. T cell defined as following: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.. MYC defined as following: Myc proto-oncogene protein (439 aa, ~49 kDa) is encoded by the human MYC gene. This protein plays a role in the regulation of transcription and cell proliferation.. 9q34 defined as following: A chromosome band present on 9q. NOTCH4 defined as following: Human NOTCH4 wild-type allele is located in the vicinity of 6p21.3 and is approximately 29 kb in length. This allele, which encodes neurogenic locus notch homolog protein 4 protein, is involved in receptor-ligand interactions and may play a role in vascular, renal and hepatic development.. malignancies defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. Notch 1 defined as following: This gene is involved in intercellular signal transduction that plays a key role in development.. NOTCH proteins defined as following: A family of transmembrane receptors with multiple extracellular EGF repeats and a DSL (notch) domain. These proteins interact with their cell-bound ligands (from the delta and serrate protein families). This interaction stimulates cell-cell signaling pathways that regulate cell fate decisions during embryogenesis.. NOTCH3 defined as following: This gene plays a role in both intercellular signaling and cell fate determination.. 7q34 defined as following: A chromosome band present on 7q. T acute lymphoblastic leukemia defined as following: A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.. hematopoietic defined as following: Pertaining to or related to the formation of blood cells.. ALL defined as following: Leukemia with an acute onset, characterized by the presence of lymphoblasts in the bone marrow and the peripheral blood. It includes the acute B lymphoblastic leukemia and acute T lymphoblastic leukemia.. NOTCH2 defined as following: This gene plays a role in cell-cell signaling.. human defined as following: Members of the species Homo sapiens.. hematological malignancies defined as following: Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.. mutated defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. T-cell Acute Lymphoblastic Leukemia defined as following: A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common..", "label": "yes"} {"id": "converted_1717", "sentence1": "Is marijuana use associated with increased risk for stroke?", "sentence2": "The illicit drugs more commonly associated with stroke are psychomotor stimulants, such as amphetamine and cocaine. Less commonly implicated are opioids and psychotomimetic drugs, including cannabis., Among 326 patients (184 males), the most frequent stroke risk factors overall were dyslipidaemia (187), smoking (161), hypertension (105) and obesity (92). Fifty-one patients used illicit drugs, mostly comprising marijuana and amphetamines., Patients in Adelaide are more likely to be obese, to be misusing marijuana and amphetamines, to suffer a cardioembolic event and to have a stroke that concurrently affects both the anterior and posterior cerebral circulation., RCVS was spontaneous in 37% of patients and secondary in the 63% others, to postpartum in 5 and to exposure to various vasoactive substances in 37, mainly cannabis, selective serotonin-recapture inhibitors and nasal decongestants., We reported two cases of young stroke associated with drug misuse. Case 1 used amphetamine, cocaine, marijuana and LSD for few yaers, and developed occlusion of a middle cerebral artery. Case 2 presented aphasia shortly after marijuana smoking., Marijuana may have accelerated stroke onset, but essential cause of stroke in this case must be protein S mutation., Cannabis is the most widely consumed among the illicit drugs worldwide, but it has only exceptionally been associated to cerebrovascular disease., We here describe 2 young patients (26 and 29 years, respectively) who suffered from ischemic stroke in temporal relation with cannabis consumption., The review of the literature on this topic reveals another 18 patients with stroke in association to cannabis use., Although a causal relationship is difficult to establish due to the widespread use of cannabis, this drug may play an etiologic role in ischemic stroke., Marijuana may trigger a myocardial infarction and have a vasospastic effect., Despite the fact that cannabis is the most widely used illicit drug, there are only a few reports associating its use with cerebrovascular disease., We describe a patient who suffered three ischaemic strokes immediately after cannabis consumption., Cannabis use may be associated with ischaemic stroke in young patients, but its mechanism is unclear., A right occipital ischemic stroke occurred in a 37-year-old Albanese man with a previously uneventful medical history, 15 min after having smoked a cigarette with approximately 250 mg of marijuana., Therefore, as the family history for cerebrovascular events, blood pressure, clotting tests, examinations for thrombophilia, vasculitis, extracranial and intracranial arteries and cardiac investigations were normal or respectively negative, the stroke was attributed to the chronic cannabis consumption., Three adolescent males had similar presentations of headache, fluctuating level of consciousness or lethargy, visual disturbance, and variable ataxia after self-administration of marijuana., Episodic marijuana use may represent a risk factor for stroke in childhood, particularly in the posterior circulation., Although several mechanisms exist by which marijuana use might contribute to the development of chronic cardiovascular conditions or acutely trigger cardiovascular events, there are few data regarding marijuana/THC use and cardiovascular disease outcomes., Reported here is the case of a previously healthy young man who smoked marijuana on a daily basis and had an occipital lobe stroke; he was found to be heterozygous for factor V Leiden., This case suggests that marijuana smoking may increase the risk of arterial thrombosis in otherwise healthy individuals who are heterozygous for factor V Leiden., Thus, chronic abuse of marijuana might be a risk factor for stroke., A 22-year-old man with a five-year history of drug and alcohol abuse presented with a left hemiparesis preceded by three transient ischaemic attacks, two of which occurred whilst smoking cannabis. Substance abuse was the only identifiable risk factor for cerebrovascular disease., Chronic marijuana smoking, however, seems to reduce CBF., Research directions might include more studies of cardiovascular disease outcomes and relationships of marijuana with cardiovascular risk factors, studies of metabolic and physiologic effects of chronic marijuana use that may affect cardiovascular disease risk, increased understanding of the role of the cannabinoid receptor system in cardiovascular regulation, and studies to determine if there is a therapeutic role for cannabinoids in blood pressure control or for neuroprotection after stroke.[SEP]Relations: Amphetamine has relations: contraindication with stroke disorder, contraindication with stroke disorder, contraindication with cardiovascular disease, contraindication with cardiovascular disease. Ischemic stroke has relations: disease_phenotype_positive with cocaine intoxication, disease_phenotype_positive with cocaine intoxication, drug_effect with Tramadol, drug_effect with Tramadol, drug_effect with Ramipril, drug_effect with Ramipril. Definitions: amphetamines defined as following: Analogs or derivatives of AMPHETAMINE. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation.. drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. opioids defined as following: Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.. visual disturbance defined as following: An interference to normal eyesight.. RCVS defined as following: Syndrome is characterized by severe headaches, with or without other acute neurological symptoms, and diffuse segmental constriction of cerebral arteries that resolves spontaneously within 3 months.. marijuana defined as following: Use of marijuana associated with abnormal psychological, social, and or occupational functioning.. hypertension defined as following: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.. ataxia defined as following: Incoordination of voluntary movements that occur as a manifestation of CEREBELLAR DISEASES. Characteristic features include a tendency for limb movements to overshoot or undershoot a target (dysmetria), a tremor that occurs during attempted movements (intention TREMOR), impaired force and rhythm of diadochokinesis (rapidly alternating movements), and GAIT ATAXIA. (From Adams et al., Principles of Neurology, 6th ed, p90). LSD defined as following: Semisynthetic derivative of ergot (Claviceps purpurea). It has complex effects on serotonergic systems including antagonism at some peripheral serotonin receptors, both agonist and antagonist actions at central nervous system serotonin receptors, and possibly effects on serotonin turnover. It is a potent hallucinogen, but the mechanisms of that effect are not well understood.. man defined as following: Members of the species Homo sapiens.. ischaemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue.. cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. cardiovascular defined as following: The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body.. headache defined as following: The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.. vasculitis defined as following: Inflammation of any one of the blood vessels, including the ARTERIES; VEINS; and rest of the vasculature system in the body.. aphasia defined as following: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia.. cannabinoids defined as following: Compounds having the cannabinoid structure. They were originally extracted from Cannabis sativa L. The most pharmacologically active constituents are TETRAHYDROCANNABINOL; CANNABINOL; and CANNABIDIOL.. stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810). cerebrovascular disease defined as following: A spectrum of pathological conditions of impaired blood flow in the brain. They can involve vessels (ARTERIES or VEINS) in the CEREBRUM, the CEREBELLUM, and the BRAIN STEM. Major categories include INTRACRANIAL ARTERIOVENOUS MALFORMATIONS; BRAIN ISCHEMIA; CEREBRAL HEMORRHAGE; and others.. CBF defined as following: CBF is an alpha/beta heterodimeric transcription factor involved in the transcriptional regulation of several genes important in hematopoiesis. The CBFalpha subunit binds directly to the enhancer core DNA sequence on target genes, whereas the beta subunit does not bind the DNA directly but increases the affinity and stabilizes the binding of the alpha subunit to the DNA.. thrombophilia defined as following: A disorder of HEMOSTASIS in which there is a tendency for the occurrence of THROMBOSIS.. cocaine defined as following: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.. Substance abuse defined as following: Any substance, including any illegal, prescription, over-the-counter agent or any other compound, used for the purpose other than indicated or used in quantities other than directed. Substances from various drug classes can be abused, such as opioids, amphetamines, analgesics, benzodiazepines, barbiturates, hallucinogens, steroids, tobacco products and alcoholic substances. A substance of abuse may act on the central nervous system (CNS) or can have an effect in other parts of the body and can lead to physical and/or physiological dependence.. dyslipidaemia defined as following: A lipoprotein metabolism disorder characterized by decreased levels of high-density lipoproteins, or elevated levels of plasma cholesterol, low-density lipoproteins and/or triglycerides.. cerebrovascular defined as following: Relating to the brain and the blood vessels that supply it..", "label": "yes"} {"id": "converted_3363", "sentence1": "Is bortezomib a Proteasome inhibitor?", "sentence2": "The proteasome-inhibitor bortezomib, The proteasome inhibitor bortezomib is effective for a variety of tumors, but not for GBM. , Proteasome inhibitor bortezomib , The proteasome inhibitor bortezomib, registered for Multiple Myeloma treatment, is currently explored for activity in solid tumors including non-small cell lung cancer (NSCLC)., Regulation of osteoblastic differentiation by the proteasome inhibitor bortezomib., The proteasome inhibitor bortezomib (also known as Velcade and PS-341) is a clinically effective antineoplastic drug that is FDA approved for treatment of hematologic malignancies such as multiple myeloma and mantle cell lymphoma., Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives., The proteasome inhibitor bortezomib is emerging as a potent anti-cancer agent., Bortezomib (Velcade™) is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM)., The proteasome inhibitor Bortezomib is used to treat multiple myeloma (MM).[SEP]Relations: Bortezomib has relations: drug_drug with Protriptyline, drug_drug with Protriptyline, drug_drug with Procarbazine, drug_drug with Procarbazine, drug_drug with Probucol, drug_drug with Probucol, drug_drug with Progesterone, drug_drug with Progesterone, drug_effect with Hepatitis, drug_effect with Hepatitis. Definitions: mantle cell lymphoma defined as following: A form of non-Hodgkin lymphoma having a usually diffuse pattern with both small and medium lymphocytes and small cleaved cells. It accounts for about 5% of adult non-Hodgkin lymphomas in the United States and Europe. The majority of mantle-cell lymphomas are associated with a t(11;14) translocation resulting in overexpression of the CYCLIN D1 gene (GENES, BCL-1).. hematologic malignancies defined as following: Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.. MM defined as following: A unit of concentration (molarity unit) equal to one thousandth of a mole (10E-3 mole) of solute per one liter of solution.. bortezomib defined as following: A pyrazine and boronic acid derivative that functions as a reversible PROTEASOME INHIBITOR. It is used as an ANTINEOPLASTIC AGENT in the treatment of MULTIPLE MYELOMA and MANTLE CELL LYMPHOMA.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. Proteasome inhibitor defined as following: Substances that inhibit proteasome, a multicatalytic cellular structure responsible for ATP-dependent proteolysis, and may induce apoptosis. Check for \"https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/C2160\" active clinical trials using this agent. (\"http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C2160\" NCI Thesaurus). solid tumors defined as following: A benign or malignant neoplasm arising from tissues that do not include fluid areas. Representative examples include epithelial neoplasms (e.g. lung carcinoma, prostate carcinoma, breast carcinoma, colon carcinoma), and neoplasms arising from the soft tissues and bones (e.g. leiomyosarcoma, liposarcoma, chondrosarcoma, osteosarcoma). Neoplasms originating from the blood or bone marrow (leukemias and myeloproliferative disorders) are not considered solid tumors.. GBM defined as following: A sheet of amorphous extracellular material upon which the basal surfaces of epithelial cells rest and is the covering surface of a glomerular capillary, interposed between the cellular elements and the underlying connective tissue.. non-small cell lung cancer defined as following: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.. multiple myeloma defined as following: A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.. antineoplastic drug defined as following: Substances that inhibit or prevent the proliferation of NEOPLASMS..", "label": "yes"} {"id": "converted_3643", "sentence1": "Is Selumetinib effective for low-grade glioma?", "sentence2": "Conclusion: Selumetinib has promising antitumor activity in children with LGG., INTERPRETATION\n\nSelumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma., These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1., Conclusion Selumetinib has promising antitumor activity in children with LGG., INTERPRETATION Selumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma., Conclusion\n\nSelumetinib has promising antitumor activity in children with LGG., INTERPRETATION\nSelumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma., These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1., These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1., INTERPRETATION: Selumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma., Selumetinib is active in recurrent, refractory, or progressive pilocytic astrocytoma harbouring common BRAF aberrations and NF1-associated paediatric low-grade glioma., These results show that selumetinib could be an alternative to standard chemotherapy for these subgroups of patients, and have directly led to the development of two Children's Oncology Group phase 3 studies comparing standard chemotherapy to selumetinib in patients with newly diagnosed paediatric low-grade glioma both with and without NF1.[SEP]Relations: Selumetinib has relations: drug_drug with Gliquidone, drug_drug with Gliquidone, drug_drug with Glasdegib, drug_drug with Glasdegib, drug_drug with Bortezomib, drug_drug with Bortezomib, drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Glipizide, drug_drug with Glipizide. Definitions: NF1 defined as following: An autosomal dominant inherited disorder (with a high frequency of spontaneous mutations) that features developmental changes in the nervous system, muscles, bones, and skin, most notably in tissue derived from the embryonic NEURAL CREST. Multiple hyperpigmented skin lesions and subcutaneous tumors are the hallmark of this disease. Peripheral and central nervous system neoplasms occur frequently, especially OPTIC NERVE GLIOMA and NEUROFIBROSARCOMA. NF1 is caused by mutations which inactivate the NF1 gene (GENES, NEUROFIBROMATOSIS 1) on chromosome 17q. The incidence of learning disabilities is also elevated in this condition. (From Adams et al., Principles of Neurology, 6th ed, pp1014-18) There is overlap of clinical features with NOONAN SYNDROME in a syndrome called neurofibromatosis-Noonan syndrome. Both the PTPN11 and NF1 gene products are involved in the SIGNAL TRANSDUCTION pathway of Ras (RAS PROTEINS).. Selumetinib defined as following: An orally active, small molecule with potential antineoplastic activity. Selumetinib is an ATP-independent inhibitor of mitogen-activated protein kinase kinase (MEK or MAPK/ERK kinase) 1 and 2. MEK 1 and 2 are dual specificity kinases that are essential mediators in the activation of the RAS/RAF/MEK/ERK pathway, are often upregulated in various cancer cells, and are drivers of diverse cellular responses, including proliferation. Inhibition of both MEK1 and 2 by selumetinib prevents the activation of MEK1/2 dependent effector proteins and transcription factors, thereby leading to an inhibition of cellular proliferation in various cancers.. pilocytic astrocytoma defined as following: A WHO grade 1, relatively circumscribed, slowly growing, often cystic astrocytoma occurring in children and young adults. Histologically it is characterized by a biphasic pattern with compacted bipolar cells associated with Rosenthal fibers and multipolar cells associated with microcysts and eosinophilic bodies/hyaline droplets. (WHO). glioma defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21). BRAF defined as following: Serine/threonine-protein kinase B-raf (766 aa, ~84 kDa) is encoded by the human BRAF gene. This protein plays a role in protein phosphorylation, mitogenesis and neuronal signal transduction..", "label": "yes"} {"id": "converted_3380", "sentence1": "Does natalizumab improve disease course of secondary progressive multiple sclerosis?", "sentence2": "INTERPRETATION: Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component., In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. , INTERPRETATION\n\nNatalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component., Natalizumab did not achieve a statistically significant primary composite disability outcome in a trial of 887 patients with secondary progressive MS , but it did demonstrate a benefit on a prespecified component of the 9-Hole Peg Test . , INTERPRETATION\nNatalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component., In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS., Natalizumab treatment for secondary progressive multiple sclerosis did not reduce progression on the primary multicomponent disability endpoint in part 1, but it did reduce progression on its upper-limb component.[SEP]Relations: multiple sclerosis has relations: disease_disease with progressive multiple sclerosis, disease_disease with progressive multiple sclerosis. Natalizumab has relations: contraindication with progressive multifocal leukoencephalopathy, contraindication with progressive multifocal leukoencephalopathy, drug_drug with Pexelizumab, drug_drug with Pexelizumab, drug_drug with Bavituximab, drug_drug with Bavituximab, drug_drug with Otelixizumab, drug_drug with Otelixizumab. Definitions: multiple sclerosis defined as following: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903). natalizumab defined as following: A humanized recombinant IgG4 monoclonal antibody directed against the alpha4 subunit of the integrins alpha4beta1and alpha4beta7 with immunomodulating, anti-inflammatory, and potential antineoplastic activities. Natalizumab binds to the alpha4-subunit of alpha4beta1 and alpha4beta7 integrins expressed on the surface of all leukocytes except neutrophils, inhibiting the alpha4-mediated adhesion of leukocytes to counter-receptor(s) such as vascular cell adhesion molecule-1 (VCAM-1); natalizumab-mediated disruption of VCAM-1 binding by these integrins may prevent the transmigration of leukocytes across the endothelium into inflamed parenchymal tissue. Integrins are cellular adhesion molecules (CAMs) that are upregulated in various types of cancer and some autoimmune diseases; alpha4beta1 integrin (VLA4) has been implicated in the survival of myeloma cells, possibly by mediating their adhesion to stromal cells..", "label": "no"} {"id": "converted_2657", "sentence1": "Are AAV vectors considered for the treatment of retinal dystrophies?", "sentence2": " These novel gene vectors aim to more safely and efficiently transduce retinal cells, expand the gene packaging capacity of AAV, and utilize new strategies to correct the varying mechanisms of dysfunction found with inherited retinal dystrophies. [SEP]Relations: retinal dystrophy in systemic or cerebroretinal lipidoses has relations: disease_disease with retinal cone dystrophy, disease_disease with retinal cone dystrophy. Definitions: retinal dystrophies defined as following: A group of disorders involving predominantly the posterior portion of the ocular fundus, due to degeneration in the sensory layer of the RETINA; RETINAL PIGMENT EPITHELIUM; BRUCH MEMBRANE; CHOROID; or a combination of these tissues..", "label": "yes"} {"id": "converted_2832", "sentence1": "Is durvalumab used for lung cancer treatment?", "sentence2": " In the phase III PACIFIC trial consolidation with durvalumab, an anti-PDL-1 antibody, was associated with survival benefit in patients diagnosed with LA-NSCLC who responded to concurrent chemoradiotherapy., METHODS: An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC., Durvalumab in non-small-cell lung cancer patients: current developments., Single-agent durvalumab showed clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly the ≥25% PD-L1+ population., Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab) and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hodgkin's lymphoma. , PURPOSE OF REVIEW: The therapeutic armamentarium for advanced non-small-cell lung cancer has evolved considerably over the past years. Immune checkpoint inhibitors targeting programmed cell death-1 such as pembrolizumab and nivolumab or programmed cell death ligand 1 such as atezolizumab, durvalumab and avelumab have shown favorable efficacy results in this patient population in the first-line and second-line setting., In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared with observation after cCRT. , ICI, such as the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab, have already been marketed for the treatment of pretreated patients with advanced NSCLC., The PACIFIC trial assessing durvalumab after standard chemoradiotherapy for locally advanced NSCLC has already met its primary endpoint and the potential of durvalumab will be reinforced if phase III randomized studies of first-line (MYSTIC trial) and second or subsequent (ARCTIC trial) lines of therapy demonstrate superiority over the current standard of care.Deciduous maxillary right first molar tooth; Universal designation B; ISO designation 54
. cerebral malaria defined as following: A condition characterized by somnolence or coma in the presence of an acute infection with PLASMODIUM FALCIPARUM (and rarely other Plasmodium species). Initial clinical manifestations include HEADACHES; SEIZURES; and alterations of mentation followed by a rapid progression to COMA. Pathologic features include cerebral capillaries filled with parasitized erythrocytes and multiple small foci of cortical and subcortical necrosis. (From Adams et al., Principles of Neurology, 6th ed, p136). malaria defined as following: Vaccines made from antigens arising from any of the four strains of Plasmodium which cause malaria in humans, or from P. berghei which causes malaria in rodents.. erythrocyte defined as following: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN..", "label": "yes"} {"id": "converted_191", "sentence1": "Are thyroid hormone receptor alpha1 mutations implicated in thyroid hormone resistance syndrome?", "sentence2": "This study reports the consequences of LT4 treatment over a prolonged period of time in 2 of the first patients with a heterozygous mutation in TRα1., Here we show that the dysregulation of the pituitary-thyroid axis was worsened by the lack of TR alpha1 in TR betaPV mice, and severe impairment of postnatal growth was manifested in TR betaPV mice deficient in TR alpha1., Heterozygous 2- to 3-week- old mice exhibit a severe retardation of post-natal development and growth, but only a minor reduction in serum thyroxine levels. , The data demonstrate a novel array of effects mediated by a dominant negative TRalpha1, and may provide important clues for identification of a potentially unrecognized human disorder and its treatment., No mutations in DNA- and hormone-binding-domains of TRbeta1 and TRalpha1 genes were found in proband, suggesting that the defect could be due to an unknown mutation in either the TR gene or a post receptor abnormality, These results demonstrate that the lack of TR alpha1 exacerbates the manifestation of RTH in TR betaPV mice. Therefore, TR alpha1 could play a compensatory role in mediating the functions of T3 in heterozygous patients with RTH. [SEP]Relations: Levothyroxine has relations: contraindication with isolated congenital growth hormone deficiency, contraindication with isolated congenital growth hormone deficiency, contraindication with thyroid crisis (disease), contraindication with thyroid crisis (disease), contraindication with acquired pituitary hormone deficiency, contraindication with acquired pituitary hormone deficiency, contraindication with non-acquired pituitary hormone deficiency, contraindication with non-acquired pituitary hormone deficiency, contraindication with combined pituitary hormone deficiencies, genetic form, contraindication with combined pituitary hormone deficiencies, genetic form. Definitions: mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. LT4 defined as following: The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.. TR defined as following: Backflow of blood from the RIGHT VENTRICLE into the RIGHT ATRIUM due to imperfect closure of the TRICUSPID VALVE..", "label": "yes"} {"id": "converted_4606", "sentence1": "Is REGN5458 a single-targeted antibody?", "sentence2": "CD3-engaging bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T cells are potent therapeutic approaches for redirecting patient T cells to recognize and kill tumors. Here we describe a fully human bsAb (REGN5458) that binds to B-cell maturation antigen (BCMA) and CD3, and compare its antitumor activities vs those of anti-BCMA CAR T cells to identify differences in efficacy and mechanism of action. [SEP]Relations: cell maturation has relations: bioprocess_protein with ANGPTL8, bioprocess_protein with ANGPTL8, bioprocess_protein with SOX8, bioprocess_protein with SOX8, bioprocess_protein with CTNNB1, bioprocess_protein with CTNNB1, bioprocess_protein with SOX18, bioprocess_protein with SOX18, bioprocess_protein with BFSP1, bioprocess_protein with BFSP1. Definitions: CAR defined as following: A cytoskeletal structure composed of actin filaments and myosin that forms beneath the plasma membrane of many cells, including animal cells and yeast cells, in a plane perpendicular to the axis of the spindle, i.e. the cell division plane. In animal cells, the contractile ring is located at the cleavage furrow. In budding fungal cells, e.g. mitotic S. cerevisiae cells, the contractile ring forms at the mother-bud neck before mitosis. [GOC:expert_jrp, GOC:sgd_curators, GOC:vw, ISBN:0805319409, ISBN:0815316194, PMID:28914606]. T cells defined as following: A subset of therapeutic autologous T-lymphocytes that express a T-cell receptor (TCR) composed of one gamma chain and one delta chain, with potential immunomodulating and antineoplastic activities. Upon administration of the therapeutic gamma delta T-lymphocytes, these cells secrete interferon-gamma (IFN-g), and exert direct killing of tumor cells. In addition, these cells activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response against tumor cells. Gamma delta T-lymphocytes play a key role in the activation of the immune system and do not require major histocompatibility complex (MHC)-mediated antigen presentation to exert their cytotoxic effect.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. chimeric antigen receptor defined as following: A cell-surface receptor that has been engineered to combine novel features and specificities from various sources in order to enhance its antigen specificity. Engineered T-cells or B-cells will produce the specialized receptor that will be capable of binding to an epitope on its target cell.. CD3 defined as following: Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).. B-cell maturation antigen defined as following: A member of the tumor necrosis factor receptor superfamily found on mature B-LYMPHOCYTES. It has specificity for B CELL ACTIVATING FACTOR and TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 13. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.. bispecific antibodies defined as following: Antibodies, often monoclonal, in which the two antigen-binding sites are specific for separate ANTIGENIC DETERMINANTS. They are artificial antibodies produced by chemical crosslinking, fusion of HYBRIDOMA cells, or by molecular genetic techniques. They function as the main mediators of targeted cellular cytotoxicity and have been shown to be efficient in the targeting of drugs, toxins, radiolabeled haptens, and effector cells to diseased tissue, primarily tumors..", "label": "no"} {"id": "converted_969", "sentence1": "Are Sidekick proteins members of the immunoglobulin superfamily?", "sentence2": "Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules--Dscam (Down's syndrome cell adhesion molecule), DscamL (refs 6-9), Sidekick-1 and Sidekick-2, Sidekick-1, a cell adhesion molecule of the immunoglobulin superfamily, is up-regulated in glomerular podocytes in the collapsing glomerulopathy of HIV-associated nephropathy (HIVAN).[SEP]Relations: cell adhesion molecule production has relations: bioprocess_protein with GOLPH3, bioprocess_protein with GOLPH3, bioprocess_protein with GCNT1, bioprocess_protein with GCNT1, bioprocess_protein with PPIA, bioprocess_protein with PPIA, bioprocess_bioprocess with cellular process, bioprocess_bioprocess with cellular process. HIV-associated nephropathy has relations: disease_disease with focal segmental glomerulosclerosis, disease_disease with focal segmental glomerulosclerosis. Definitions: HIV-associated nephropathy defined as following: Renal syndrome in human immunodeficiency virus-infected patients characterized by nephrotic syndrome, severe proteinuria, focal and segmental glomerulosclerosis with distinctive tubular and interstitial changes, enlarged kidneys, and peculiar tubuloreticular structures. The syndrome is distinct from heroin-associated nephropathy as well as other forms of kidney disease seen in HIV-infected patients.. cell adhesion molecule defined as following: A cell adhesion molecule that contains extracellular immunoglobulin V and C2 domains. It mediates homophilic and heterophilic cell-cell adhesion independently of calcium, and acts as a tumor suppressor in NON-SMALL-CELL LUNG CANCER (NSCLC) cells. Its interaction with NATURAL KILLER CELLS is important for their cytotoxicity and its expression by MAST CELLS plays a role in their interaction with neurons; it may also function in synapse assembly, nerve growth and differentiation..", "label": "yes"} {"id": "converted_688", "sentence1": "Is Ctf4 involved in sister chromatid cohesion establishment?", "sentence2": "In addition to Eco1, several other factors contribute to cohesion establishment, including Ctf4, Ctf18, Tof1, Csm3, Chl1 and Mrc1, but little is known about their roles. Here, we show that each of these factors facilitates cohesin acetylation. Moreover, the absence of Ctf4 and Chl1, but not of the other factors, causes a synthetic growth defect in cells lacking Eco1. Distinct from acetylation defects, sister chromatid cohesion in ctf4Δ and chl1Δ cells is not improved by removing Wapl, Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment, Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1, Influence of the human cohesion establishment factor Ctf4/AND-1, Here, we used Xenopus egg extracts to show that AND-1 and Tim1-Tipin, homologues of Saccharomyces cerevisiae Ctf4 and Tof1-Csm3, respectively, are associated with the replisome and are required for proper establishment of the cohesion observed in the M-phase extracts, These data defined two cohesion pathways, one containing CSM3, TOF1, CTF4, and CHL1, and the second containing MRC1, CTF18, CTF8, and DCC1, Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion, Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks, WSS1 was also found to interact genetically with SGS1, TOP3, SRS2 and CTF4, which are involved in recombination, repair of replication forks and the establishment of sister chromatid cohesion, The catalytic subunit of budding yeast Polalpha (Pol1p) has been shown to associate in vitro with the Spt16p-Pob3p complex, a component of the nucleosome reorganization system required for both replication and transcription, and with a sister chromatid cohesion factor, Ctf4p, Constituents of the replication fork, such as the DNA polymerase alpha-binding protein Ctf4, contribute to cohesion in ways that are poorly understood, Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3., Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion., Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion., Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks., Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-alpha-associated protein Ctf4 is essential for chromatid disjunction during meiosis II., Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion., We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint., We show here that CTF8, CTF4 and a helicase encoded by CHL1 are required for efficient sister chromatid cohesion in unperturbed mitotic cells, and provide evidence that Chl1 functions during S-phase., In budding yeast, a specialized replication factor C called RF-C(Ctf18/Dcc1/Ctf8) and the DNA-polymerase-alpha-associated protein Ctf4 are required to maintain sister-chromatid cohesion in cells arrested for long periods in mitosis., The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion., Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion., Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment., Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment., Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion, Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3, Establishment of sister chromatid cohesion at the S. cerevisiae replication fork.[SEP]Relations: DDX11 has relations: bioprocess_protein with establishment of sister chromatid cohesion, bioprocess_protein with establishment of sister chromatid cohesion, bioprocess_protein with positive regulation of sister chromatid cohesion, bioprocess_protein with positive regulation of sister chromatid cohesion, bioprocess_protein with sister chromatid cohesion, bioprocess_protein with sister chromatid cohesion, molfunc_protein with chromatin binding, molfunc_protein with chromatin binding, bioprocess_protein with positive regulation of chromatin binding, bioprocess_protein with positive regulation of chromatin binding. Definitions: MRC1 defined as following: This gene is involved in endocytosis of glycoproteins by macrophages.. Smc3 defined as following: Human SMC3 wild-type allele is located in the vicinity of 10q25 and is approximately 37 kb in length. This allele, which encodes structural maintenance of chromosomes protein 3, is involved in the regulation of chromosome migration during mitosis.. Wapl defined as following: This gene is involved in both DNA replication and sister chromatid cohesion.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. S. cerevisiae defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. spindle defined as following: The array of microtubules and associated molecules that forms between opposite poles of a eukaryotic cell during mitosis or meiosis and serves to move the duplicated chromosomes apart. [ISBN:0198547684]. TOP3 defined as following: Human TOP3A wild-type allele is located within 17p12-p11.2 and is approximately 41 kb in length. This allele, which encodes DNA topoisomerase 3-alpha protein, is involved in the ATP-independent breakage of negatively supercoiled single-stranded DNA and subsequent passage/rejoining of the broken DNA.. S-phase defined as following: Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.. human defined as following: Members of the species Homo sapiens.. catalytic subunit defined as following: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary..", "label": "yes"} {"id": "converted_3708", "sentence1": "Does ESN364 activate the hypothalamic-pituitary-gonadal axis?", "sentence2": "Oral administration of the NK3R antagonist, ESN364, suppressed the hypothalamic-pituitary-gonadal axis in healthy volunteers by selective modulation of gonadotropin secretion, leading to a restrained decrease in ovarian hormone levels in women.[SEP]Definitions: NK3R defined as following: Human TACR3 wild-type allele is located within 4q25 and is approximately 130 kb in length. This allele, which encodes neuromedin K receptor protein, plays a role in the modulation of receptor interactions involving the neuropeptide tachykinin..", "label": "no"} {"id": "converted_3144", "sentence1": "Is the protein Asporin related to disease?", "sentence2": "Accumulating evidence demonstrates the involvement of asporin in OA pathogenesis., Asporin has been reported as a tumor suppressor in breast cancer, while asporin-activated invasion has been described in gastric cancer., Asporin has been implicated as an oncogene in various types of human cancers; , These results suggested that asporin promoted the tumor growth and metastasis of CRC, and it could be a potential therapeutic target for CRC patients in future., Our results suggest that ASPN is a stromally expressed biomarker that correlates with disease progression, and is observed in reactive stroma. [SEP]Relations: osteoarthritis susceptibility has relations: disease_protein with ASPN, disease_protein with ASPN, disease_protein with ETFA, disease_protein with ETFA, disease_protein with ACTB, disease_protein with ACTB, disease_protein with ASTN2, disease_protein with ASTN2, disease_protein with COMP, disease_protein with COMP. Definitions: oncogene defined as following: Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of \"v-\" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix \"c-\" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.. breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. human defined as following: Members of the species Homo sapiens.. CRC defined as following: The disappearance of all signs of cancer, including the absence of a detectable disease-related genetic abnormality, as determined by techniques such as karyotyping or FISH, in response to treatment.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. gastric cancer defined as following: A primary or metastatic malignant neoplasm involving the stomach.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown..", "label": "yes"} {"id": "converted_3387", "sentence1": "Has ZP-PTH been tested in a phase II clinical trial?", "sentence2": "This system was successfully tested in a Phase 2 clinical trial for the treatment of post-menopausal women with osteoporosis.[SEP]Relations: stenosis or atrophy of the coronary ostium has relations: disease_disease with abnormal origin or aberrant course of coronary artery, disease_disease with abnormal origin or aberrant course of coronary artery.", "label": "yes"} {"id": "converted_450", "sentence1": "Can SUMO affect calcium homeostasis?", "sentence2": "Increasing SUMOylation levels correlated inversely with calcium influx in sensory neurons., CRMP2 deSUMOylation by SUMO proteases SENP1 and SENP2 normalized calcium influx to those in the CRMP2AAA mutant., Thus, our results identify a novel role for SUMO modification in CRMP2/CaV2.2 signaling pathway, Moreover, SUMO1 overexpression in isolated cardiomyocytes augmented contractility and accelerated Ca(2+) decay., RIM1α SUMOylation at lysine residue K502 facilitates the clustering of CaV2.1 calcium channels and enhances the Ca(2+) influx necessary for vesicular release, whereas non-SUMOylated RIM1α participates in the docking/priming of synaptic vesicles and maintenance of active zone structure. , Identification and characterization of a SUMO-1 conjugation system that modifies neuronal calcium/calmodulin-dependent protein kinase II in Drosophila melanogaster.[SEP]Relations: Protein S human has relations: drug_drug with Calcium Phosphate, drug_drug with Calcium Phosphate, drug_drug with Calcium Phosphate, drug_drug with Calcium Phosphate, drug_drug with Calcium carbonate, drug_drug with Calcium carbonate, drug_drug with Calcium carbonate, drug_drug with Calcium carbonate, drug_drug with Calcium threonate, drug_drug with Calcium threonate. Definitions: SUMO1 defined as following: Small ubiquitin-related modifier 1 (101 aa, ~12 kDa) is encoded by the human SUMO1 gene. This protein plays a role in post-translational protein modification.. SENP1 defined as following: Sentrin-specific protease 1 (644 aa, ~73 kDa) is encoded by the human SENP1 gene. This protein is involved in both caspase activation and protein desumoylation.. SENP2 defined as following: Human SUMO1 wild-type allele is located in the vicinity of 2q33 and is approximately 32 kb in length. This allele, which encodes small ubiquitin-related modifier 1 protein, is involved in the post-translational modification of proteins.. sensory neurons defined as following: Specialized afferent neurons capable of transducing sensory stimuli into NERVE IMPULSES to be transmitted to the CENTRAL NERVOUS SYSTEM. Sometimes sensory receptors for external stimuli are called exteroceptors; for internal stimuli are called interoceptors and proprioceptors.. synaptic vesicles defined as following: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents.. cardiomyocytes defined as following: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC)..", "label": "yes"} {"id": "converted_3639", "sentence1": "Is poliosis circumscripta another term for a white or unpigmented patch of hair or skin?", "sentence2": "\"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicle, Although traditionally known as \"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicles, can involve any hairy area on the body including the scalp, eyebrows, and eyelashes., Although traditionally known as \" white forelock , \" poliosis circumscripta , defined as a localized patch of white hair in a group of hair follicles , can involve any hairy area on the body including the scalp , eyebrows , and eyelashes, Although traditionally known as \"white forelock,\" poliosis circumscripta, defined as a localized patch of white hair in a group of hair follicles, can involve any hairy area on the body including the scalp, eyebrows, and eyelashes.[SEP]Relations: eyelash has relations: anatomy_anatomy with strand of hair, anatomy_anatomy with strand of hair. muscle structure has relations: anatomy_anatomy with insect adult somatic muscle, anatomy_anatomy with insect adult somatic muscle, anatomy_anatomy with somatic muscle, anatomy_anatomy with somatic muscle, anatomy_anatomy with urethra muscle tissue, anatomy_anatomy with urethra muscle tissue, anatomy_anatomy with anatomical structure, anatomy_anatomy with anatomical structure. Definitions: eyelashes defined as following: The hairs which project from the edges of the EYELIDS.. eyebrows defined as following: Curved rows of HAIR located on the upper edges of the eye sockets.. scalp defined as following: The outer covering of the calvaria. It is composed of several layers: SKIN; subcutaneous connective tissue; the occipitofrontal muscle which includes the tendinous galea aponeurotica; loose connective tissue; and the pericranium (the PERIOSTEUM of the SKULL)..", "label": "yes"} {"id": "converted_949", "sentence1": "Do R-loops tend to form at sites of DNA replication?", "sentence2": "Escherichia coli rnhA mutants devoid of RNase HI exhibit constitutive stable DNA replication, cSDR, which is thought to be initiated from R-loops stabilized in the absence of RNase HI., We propose that the organized structure of the R-loop is critical for primer RNA function in vivo with important implications for the RNA processing and DNA replication machinery., The precursor primer RNA exists as a persistent RNA-DNA hybrid, known as an R-loop, formed during transcription through the replication origin (Xu, B., and Clayton, D. A. (1996) EMBO J. 15, 3135-3143)., We found that overproduction of RecG protein drastically decreased copy numbers of ColE1-type plasmids, which require R-loop formation between the template DNA and a primer RNA transcript (RNA II) for the initiation of replication., These results suggest that overproduced RecG inhibits the initiation of replication by prematurely resolving the R-loops formed at the replication origin region of these plasmids with its unique helicase activity. The possibility that RecG regulates the initiation of a unique mode of DNA replication, oriC-independent constitutive stable DNA replication, by its activity in resolving R-loops is discussed., We propose that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome. This would allow replication to proceed while the original block is repaired or bypassed, Furthermore, increased RNaseH expression significantly alleviated genomic instability in deficient fibroblasts suggesting that cotranscriptional R-loops formation contributes to the genesis of replication-dependent DSBs in these cells., Transcription is an important source of replicative stress and consequently, maintenance of genome integrity requires the protection of chromosomes from the deleterious effects arising from the interaction between nascent RNAs and template DNA, leading to stable DNA-RNA hybrids (R-loop) formation., Strikingly, we found that attenuation of replication strongly suppresses R-loop-mediated DNA rearrangements in both E. coli and HeLa cells., More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stabilit, R-loop-mediated genomic instability is caused by impairment of replication fork progression, When any of these processes are not properly coordinated, aberrant outcomes such as fork reversal and R-loop formation arise and trigger unscheduled recombinogenic events and genome rearrangements. , Many studies show that cells can manage R loop formation with efficiency, and can also process the R-loops already formed in the cell, and by which, the bad effects of R-loops on DNA replication, gene mutation and homologous recombination can be regulated., Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells. , In agreement with this, we found that R-loops co-localize with the ORC within the same CpG island region in a significant fraction of these efficient replication origins, precisely at the position displaying the highest density of G4 motifs. , connection between transcription and replication in human cells and suggests that R-loop dysregulation at CpG island promoter-origins might contribute to the phenotype of DNA replication abnormalities and loss of genome integrity detected in cancer cells., We show that RNA:DNA hybrids (R-loops) form at sites of transcription/replication collisions and that RNase H1 functions to suppress CFS instability., R-loops and initiation of DNA replication in human cells: a missing link?, Stable RNA-DNA hybrids (R-loops) prime the initiation of replication in Escherichia coli cells., We propose that downstream of a replication block, RNA at R-loops is extended by DNA polymerase I, opening up the DNA duplex and leading to the recruitment of the replisome., Immediately after infection, RNA-DNA hybrids (R-loops) occur on (at least some) replication origins, with the annealed RNA serving as a primer for leading-strand synthesis in one direction., Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells., ColE1 plasmid origins of replication and oriK sites initiate primosome assembly by an RNA-DNA hybrid structure known as R-loop., This scenario builds on the connection between transcription and replication in human cells and suggests that R-loop dysregulation at CpG island promoter-origins might contribute to the phenotype of DNA replication abnormalities and loss of genome integrity detected in cancer cells., The multiple cleavage sites on the R-loop substrate match the priming sites observed in vivo, suggesting that RNase MRP alone is capable of generating virtually all of the leading-strand replication primers., Mechanisms of primer RNA synthesis and D-loop/R-loop-dependent DNA replication in Escherichia coli., Alternative oriC-independent modes of replication initiation are possible, one of which is constitutive stable DNA replication (cSDR) from transcription-associated RNA-DNA hybrids or R-loops., Our results suggest that Top1 execute this function by suppressing the formation of DNA-RNA hybrids during transcription, these so-called R-loops interfering with the progression of replication forks., Critical role of R-loops in processing replication blocks., The possibility that RecG regulates the initiation of a unique mode of DNA replication, oriC-independent constitutive stable DNA replication, by its activity in resolving R-loops is discussed., Competition between the RNA transcript and the nontemplate DNA strand during R-loop formation in vitro: a nick can serve as a strong R-loop initiation site., More importantly, we then show that R-loop formation causes DNA replication fork stalling, and that this in fact underlies the effects of R loops on genomic stability. , Consistent with this hypothesis, the 3' ends of the mitochondrial R-loop formed by in vitro transcription are located close to the initiation sites of the mitochondrial DNA replication. , A hybrid G-quadruplex structure formed between RNA and DNA explains the extraordinary stability of the mitochondrial R-loop., Previous studies have shown that the newly synthesized primers form a stable and persistent RNA-DNA hybrid, a R-loop, near the leading-strand origin of DNA replication. , Escherichia coli rnhA mutants devoid of RNase HI exhibit constitutive stable DNA replication, cSDR, which is thought to be initiated from R-loops stabilized in the absence of RNase HI. [SEP]Relations: HELLS has relations: bioprocess_protein with DNA methylation-dependent heterochromatin assembly, bioprocess_protein with DNA methylation-dependent heterochromatin assembly, anatomy_protein_present with lymph node, anatomy_protein_present with lymph node, bioprocess_protein with maintenance of DNA methylation, bioprocess_protein with maintenance of DNA methylation. snRNA transcription by RNA polymerase III has relations: bioprocess_protein with ZC3H8, bioprocess_protein with ZC3H8, bioprocess_protein with ELL, bioprocess_protein with ELL. Definitions: genome defined as following: Anatomical set of genes in all the chromosomes.. Top1 defined as following: DNA topoisomerase 1 (765 aa, ~91 kDa) is encoded by the human TOP1 gene. This protein plays a role in the regulation of DNA topology.. HeLa cells defined as following: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. RNase defined as following: An enzyme that catalyzes the endonucleolytic cleavage of pancreatic ribonucleic acids to 3'-phosphomono- and oligonucleotides ending in cytidylic or uridylic acids with 2',3'-cyclic phosphate intermediates. EC 3.1.27.5.. R-loop defined as following: An RNA-DNA hybrid structure formed when newly transcribed RNA remains bound to its DNA template. Stability of R-loops may play a role in GENETIC INSTABILITY.. RNAs defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). cancer cells defined as following: Cells of, or derived from, a malignant tumor.. mutants defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. ORC defined as following: A multisubunit complex that is located at the replication origins of a chromosome. [GOC:elh]. primosome defined as following: Any of a family of protein complexes that form at the origin of replication or stalled replication forks and function in replication primer synthesis in all organisms. Early complexes initiate double-stranded DNA unwinding. The core unit consists of a replicative helicase and a primase. The helicase further unwinds the DNA and recruits the polymerase machinery. The primase synthesizes RNA primers that act as templates for complementary stand replication by the polymerase machinery. The primosome contains a number of associated proteins and protein complexes and contributes to the processes of replication initiation, lagging strand elongation, and replication restart. [GOC:bhm, GOC:mah, PMID:21856207]. position defined as following: A reference to the alignment of an object, a particular situation or view of a situation, or the location of an object.. mitochondrial defined as following: The distribution of mitochondria, including the mitochondrial genome, into daughter cells after mitosis or meiosis, mediated by interactions between mitochondria and the cytoskeleton. [GOC:mcc, PMID:10873824, PMID:11389764]. plasmids defined as following: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.. primer defined as following: Short DNA oligonucleotide chains used to prime DNA (and in some cases RNA) synthesis.. Escherichia coli defined as following: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.. fork defined as following: An orthopedic manual surgical instrument is a nonpowered hand-held device intended for medical purposes to manipulate tissue, or for use with other devices in orthopedic surgery. This generic type of device includes the cerclage applier, awl, bender, drill brace, broach, burr, corkscrew, countersink, pin crimper, wire cutter, prosthesis driver, extractor, file, fork, needle holder, impactor, bending or contouring instrument, compression instrument, passer, socket positioner, probe, femoral neck punch, socket pusher, reamer, rongeur, scissors, screwdriver, bone skid, staple driver, bone screw starter, surgical stripper, tamp, bone tap, trephine, wire twister, and wrench.. mitochondrial DNA defined as following: Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.. sites defined as following: A position in relation to its surroundings.. infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. CFS defined as following: A syndrome characterized by persistent or recurrent fatigue, diffuse musculoskeletal pain, sleep disturbances, and subjective cognitive impairment of 6 months duration or longer. Symptoms are not caused by ongoing exertion; are not relieved by rest; and result in a substantial reduction of previous levels of occupational, educational, social, or personal activities. Minor alterations of immune, neuroendocrine, and autonomic function may be associated with this syndrome. There is also considerable overlap between this condition and FIBROMYALGIA. (From Semin Neurol 1998;18(2):237-42; Ann Intern Med 1994 Dec 15;121(12): 953-9). gene mutation defined as following: A change in the nucleotide sequence of the TAF1 gene.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. R-loops defined as following: An RNA-DNA hybrid structure formed when newly transcribed RNA remains bound to its DNA template. Stability of R-loops may play a role in GENETIC INSTABILITY..", "label": "yes"} {"id": "converted_2226", "sentence1": "Is there any involvement of L1 retrotransposition in the Rett syndrome?", "sentence2": "Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that patients with Rett syndrome (RTT), carrying MeCP2 mutations, have increased susceptibility for L1 retrotransposition. Our data demonstrate that L1 retrotransposition can be controlled in a tissue-specific manner and that disease-related genetic mutations can influence the frequency of neuronal L1 retrotransposition. Our findings add a new level of complexity to the molecular events that can lead to neurological disorders., Furthermore, some neurological diseases, such as Rett syndrome and ataxia telangiectasia, misregulate L1 retrotransposition, which could contribute to some pathological aspects. , Recent studies indicate that long interspersed nuclear element-1 (L1) are mobilized in the genome of human neural progenitor cells and enhanced in Rett syndrome and ataxia telangiectasia. , In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients., Furthermore, some neurological diseases, such as Rett syndrome and ataxia telangiectasia, misregulate L1 retrotransposition, which could contribute to some pathological aspects., Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that patients with Rett syndrome (RTT), carrying MeCP2 mutations, have increased susceptibility for L1 retrotransposition., In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients., Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that patients with Rett syndrome (RTT), carrying MeCP2 mutations, have increased susceptibility for L1 retrotransposition, Furthermore, some neurological diseases, such as Rett syndrome and ataxia telangiectasia, misregulate L1 retrotransposition, which could contribute to some pathological aspects, Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that patients with Rett syndrome (RTT), carrying MeCP2 mutations, have increased susceptibility for L1 retrotransposition., Furthermore, some neurological diseases, such as Rett syndrome and ataxia telangiectasia, misregulate L1 retrotransposition, which could contribute to some pathological aspects., Recent studies indicate that long interspersed nuclear element-1 (L1) are mobilized in the genome of human neural progenitor cells and enhanced in Rett syndrome and ataxia telangiectasia.[SEP]Relations: Rett syndrome has relations: disease_protein with PTPN1, disease_protein with PTPN1, disease_protein with STXBP1, disease_protein with STXBP1, disease_phenotype_positive with Abnormality of the dentition, disease_phenotype_positive with Abnormality of the dentition, disease_protein with NTNG1, disease_protein with NTNG1, disease_protein with FOXG1, disease_protein with FOXG1. Definitions: ataxia telangiectasia defined as following: An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).. genome defined as following: Anatomical set of genes in all the chromosomes.. human defined as following: Members of the species Homo sapiens.. genetic mutations defined as following: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.. MeCP2 defined as following: Methyl-CpG-binding protein 2 (486 aa, ~52 kDa) is encoded by the human MECP2 gene. This protein plays a role in the repression of transcription through binding methylated DNA.. L1 defined as following: A long interspersed element (LINE) found in mammals. The LINE-1 element is the only active LINE in humans and is approximately 6,000 base pairs long. This nucleotide sequence consists of two non-overlapping open reading frames (ORF) flanked by a 5' untranslated region (UTR), which contains a strong RNA polymerase II promoter sequence, and target side duplications. The first ORF encodes a 500 amino acid, ~40 kDa leucine zipper-containing RNA-binding protein. The second ORF encodes an ~150 kDa protein that has endonuclease and reverse transcriptase activity. Increased LINE-1 copy number is associated with cancer and neuropathy.. neurological disorders defined as following: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.. Rett syndrome defined as following: This gene plays a role in both the recognition of DNA methylation and the regulation of transcription..", "label": "yes"} {"id": "converted_1484", "sentence1": "Can clonidine be used to reduce agitation in children.", "sentence2": "Children receiving clonidine immediately after anesthesia induction had statistically significant improvement in postoperative agitation at the 15-minute mark (P = .096) and last score obtained (P = .095) using the Watcha scale., Clonidine has proven to be effective in reducing the incidence of post-operative agitation at a higher dose (3 and 2 μg kg⁻¹)., Post-anaesthetic agitation was observed in two patients (6.6%) in group 1, eight patients (26.6%) in group 2 as compared to 12 patients (40%) in group 3 after 15 min of post-operative observation., The mean scores in group 1 at 15 and 30 min were significantly lower than those in group 3 (P value <0.05), Caudal clonidine at a lower dose (1 μg kg⁻¹) could be effective in reducing the incidence of sevoflurane-induced emergence agitation in children undergoing urogenital and lower limb surgery without any significant adverse effects., Only the 4 microg kg-1 dose of clonidine was associated with a significant reduction in emergence agitation., Fewer children in the clonidine 4 microg kg-1 group displayed agitation (25%) than in the midazolam group (60%) (P=0.025)., In comparison with midazolam, clonidine 4 microg kg-1 reduced sevoflurane-induced emergence agitation without increasing postoperative side-effects., Prophylactic use of clonidine against sevoflurane-induced agitation may represent a new and promising application., One hundred and twenty children were included in this study: 59 of whom received clonidine, and 61 placebo; 41% of those in the placebo group exhibited moderate-severe EA compared with only 22% of those in the clonidine group (P < 0.03)., Findings demonstrate that i.v. clonidine administered after induction of anesthesia significantly reduces the incidence of EA in young children, but is associated with sleepiness postoperatively., Clonidine could not prevent agitation (incidence 54%, 13/24), Clonidine 1.5 microg/kg did not differ from placebo with respect to postoperative agitation., Clonidine is effective in treating sevoflurane-induced postanesthesia agitation in children., Pain and discomfort scores were significantly decreased in the clonidine group; the incidence of agitation was reduced by 57% (P = 0.029) and the incidence of severe agitation by 67% (P = 0.064). Relative risks for developing agitation and severe agitation were 0.43 (95% confidence interval, 0.24-0.78) and 0.32 (0.09-1.17), respectively., Clonidine produces a substantial reduction in the risk of postsevoflurane agitation in children., Agitation was observed in 12 midazolam-treated and five clonidine-treated patients (P=0.05)., Compared with midazolam, clonidine premedication reduced agitation during sevoflurane induction., Clonidine 3 micrograms kg-1 prevented agitation after sevoflurane anaesthesia, independently of the route of administration. The effect of clonidine appears to be dose-dependent, as an epidural dose of 1 microgram kg-1 failed to reduce it., Clonidine prevents sevoflurane-induced agitation in children., In 16 placebo and 2 clonidine-treated patients agitation was observed (P < 0.001), In 6 patients of the Placebo group, agitation was graded as severe, whereas none of the patients in the Clonidine group developed severe agitation (P = 0.02)., We conclude that clonidine effectively prevents agitation after sevoflurane anesthesia., Clonidine 2 microg/kg IV after anesthetic induction effectively reduces the incidence of agitation without resulting in clinically relevant bradycardia and hypotension., Children receiving clonidine prior to undergoing strabismus surgery have a small but noticeable reduction in postoperative agitation, stay slightly longer in the post-anesthesia care unit, and have higher rates of parent satisfaction., We report three cases of preoperative use of intranasal clonidine in pediatric patients, all for different indications. One patient was treated for preoperative agitation and hallucinations associated with oral midazolam. One patient was given clonidine as a premedicant. The third patient was treated for preoperative agitation and hypertension. All three patients had subjective resolution of indicated symptoms and none experienced adverse outcomes., Oral or intravenous clonidine has been successfully used for the prevention of sevoflurane-induced agitation during emergence from anaesthesia.[SEP]Relations: Agitation has relations: drug_effect with Clonidine, drug_effect with Clonidine. Clonidine has relations: drug_effect with Agitation, drug_effect with Agitation, drug_effect with Anxiety, drug_effect with Anxiety, contraindication with anxiety disorder, contraindication with anxiety disorder, drug_effect with Headache, drug_effect with Headache. Definitions: sleepiness defined as following: Compelling urge to sleep.. urogenital defined as following: All the organs involved in reproduction and the formation and release of URINE. It includes the kidneys, ureters, BLADDER; URETHRA, and the organs of reproduction - ovaries, UTERUS; FALLOPIAN TUBES; VAGINA; and CLITORIS in women and the testes; SEMINAL VESICLES; PROSTATE; seminal ducts; and PENIS in men.. agitation defined as following: A state of restlessness associated with unpleasant feelings of irritability and tension. Causes include pain, stress, fever, alcohol and nicotine withdrawal, cocaine and hallucinogenic drugs use, depression, bipolar disorders, and schizophrenia.. hypotension defined as following: Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.. Clonidine defined as following: An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.. EA defined as following: A compound that inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. This compound has been classified as a loop or high ceiling diuretic.. hypertension defined as following: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.. midazolam defined as following: A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.. hallucinations defined as following: Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with MENTAL DISORDERS.. Oral defined as following: The introduction of a substance to the mouth or into the gastrointestinal tract by the way of the mouth, usually for systemic action. It is the most common, convenient, and usually the safest and least expensive route of drug administration, but it uses the most complicated pathway to the tissues and bioavailability varies. The disadvantages of method are hepatic first pass metabolism and enzymatic degradation of the drug within the gastrointestinal tract. This prohibits oral administration of certain classes of drugs especially peptides and proteins.. clonidine defined as following: An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION..", "label": "yes"} {"id": "converted_725", "sentence1": "Is acid alpha-glucosidase the enzyme that causes Pompe disease when mutant?", "sentence2": "Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA)), Pompe disease is a systemic metabolic disorder characterized by lack of acid-alpha glucosidase (GAA) resulting in ubiquitous lysosomal glycogen accumulation, Pompe disease is an autosomal recessive myopathic disorder caused by the deficiency of lysosomal acid α-glucosidase (GAA), Acid α-glucosidase deficiency, that is, Pompe disease, is a glycogenosis for which enzyme replacement therapy (ERT) is available, The analysis revealed that the amino acid substitutions causing a processing or transport defect responsible for Pompe disease were widely spread over all of the five domains comprising the acid alpha-glucosidase., Pompe disease is a lysosomal storage disease (LSD) caused by a deficiency in the lysosomal enzyme acid alpha-glucosidase., Glycogen storage disease type II (GSDII; Pompe disease or acid maltase deficiency) is an autosomal recessive disorder caused by lysosomal acid alpha-glucosidase (AalphaGlu) deficiency and manifests predominantly as skeletal muscle weakness., Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease., The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types., Pompe disease (glycogen storage disease II) is caused by mutations in the acid alpha-glucosidase gene., Glycogen storage disease type II (Pompe disease) is inherited by autosomal recessive transmission and caused by a deficiency of acid alpha-glucosidase (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen., Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA)., Demonstration of acid alpha-glucosidase in different types of Pompe disease by use of an immunochemical method., Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists., Deficiency of acid alpha glucosidase (GAA) causes Pompe disease, which is usually fatal if onset occurs in infancy., Ambulatory electrocardiogram analysis in infants treated with recombinant human acid alpha-glucosidase enzyme replacement therapy for Pompe disease., Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase., Determination of acid alpha-glucosidase activity in blood spots as a diagnostic test for Pompe disease., The pharmacological chaperone AT2220 increases the specific activity and lysosomal delivery of mutant acid alpha-glucosidase, and promotes glycogen reduction in a transgenic mouse model of Pompe disease, Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease, Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzyme, Although many lysosomal disorders are corrected by a small amount of the missing enzyme, it has been generally accepted that 20-30% of normal acid alpha-glucosidase (GAA) activity, provided by gene or enzyme replacement therapy, would be required to reverse the myopathy and cardiomyopathy in Pompe disease, The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types, As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid alpha-glucosidase gene (6(neo)/6(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter, Glycogen-storage disease type II, Pompe disease, is caused by the deficiency of acid alpha-D-glucosidase in lysosome, Pompe disease (glycogen storage disease II) is caused by mutations in the acid alpha-glucosidase gene, Glycogen storage disease type II (Pompe disease) is inherited by autosomal recessive transmission and caused by a deficiency of acid alpha-glucosidase (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen, Glycogen stored in skeletal but not in cardiac muscle in acid alpha-glucosidase mutant (Pompe) mice is highly resistant to transgene-encoded human enzyme., Structural modeling of mutant alpha-glucosidases resulting in a processing/transport defect in Pompe disease., Replacing acid alpha-glucosidase in Pompe disease: recombinant and transgenic enzymes are equipotent, but neither completely clears glycogen from type II muscle fibers., The pharmacological chaperone AT2220 increases the specific activity and lysosomal delivery of mutant acid alpha-glucosidase, and promotes glycogen reduction in a transgenic mouse model of Pompe disease., Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. , Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease., We describe an improved method for detecting deficiency of the acid hydrolase, alpha-1,4-glucosidase in leukocytes, the enzyme defect in glycogen storage disease Type II (Pompe disease)., Acid alpha-glucosidase (GAA) deficiency causes Pompe disease,, Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase. Trials with recombinant human acid alpha-glucosidase enzyme replacement therapy (ERT) show a decrease in left ventricular mass and improved function., Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase. Due to virtual absence of acid alpha-glucosidase, patients with classical infantile Pompe disease develop progressive cardiomyopathy, skeletal muscle weakness and respiratory insufficiency leading to death in early infancy., Pompe disease is caused by the congenital deficiency of the lysosomal enzyme acid alpha-glucosidase., The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease,, Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA). Recently, small molecule pharmacological chaperones have been shown to increase protein stability and cellular levels for mutant lysosomal enzymes and have emerged as a new therapeutic strategy for the treatment of LSDs., Acid alpha-glucosidase (GAA) deficiency causes Pompe disease, a lethal lysosomal glycogen storage disease for which no effective treatment currently exists., Infantile Pompe disease is caused by deficiency of lysosomal acid alpha-glucosidase., Glycogen-storage disease type II, Pompe disease, is caused by the deficiency of acid alpha-D-glucosidase in lysosome., Structural modeling of mutant alpha-glucosidases resulting in a processing/transport defect in Pompe disease., Pompe disease is a lysosomal storage disorder (LSD) caused by mutations in the gene that encodes acid alpha-glucosidase (GAA)., Structural study on a mutant acid alpha-glucosidase in silico combined with biochemical investigation is useful for understanding the molecular pathology of Pompe disease., Ambulatory electrocardiogram analysis in infants treated with recombinant human acid alpha-glucosidase enzyme replacement therapy for Pompe disease., Mutations in alpha-glucosidase cause accumulation of glycogen in lysosomes, resulting in Pompe disease, a lysosomal storage disorder., Pompe disease is an autosomal recessive muscle-wasting disorder caused by the deficiency of the lysosomal enzyme acid alpha-glucosidase., Infantile Pompe disease is a fatal genetic muscle disorder caused by a deficiency of acid alpha-glucosidase, a glycogen-degrading lysosomal enzyme.[SEP]Relations: glycogen storage disease has relations: disease_disease with glycogen storage disease due to muscle beta-enolase deficiency, disease_disease with glycogen storage disease due to muscle beta-enolase deficiency, disease_disease with glycogen storage disease due to acid maltase deficiency, late-onset, disease_disease with glycogen storage disease due to acid maltase deficiency, late-onset, disease_disease with glycogen storage disease due to acid maltase deficiency, infantile onset, disease_disease with glycogen storage disease due to acid maltase deficiency, infantile onset. GAA has relations: disease_protein with glycogen storage disease due to acid maltase deficiency, late-onset, disease_protein with glycogen storage disease due to acid maltase deficiency, late-onset, disease_protein with glycogen storage disease due to acid maltase deficiency, infantile onset, disease_protein with glycogen storage disease due to acid maltase deficiency, infantile onset. Definitions: autosomal recessive disorder defined as following: An inherited disorder manifested only when two copies of a mutated gene are present.. alpha-glucosidase defined as following: Enzymes that catalyze the exohydrolysis of 1,4-alpha-glucosidic linkages with release of alpha-glucose. Deficiency of alpha-1,4-glucosidase may cause GLYCOGEN STORAGE DISEASE TYPE II.. LSD defined as following: Semisynthetic derivative of ergot (Claviceps purpurea). It has complex effects on serotonergic systems including antagonism at some peripheral serotonin receptors, both agonist and antagonist actions at central nervous system serotonin receptors, and possibly effects on serotonin turnover. It is a potent hallucinogen, but the mechanisms of that effect are not well understood.. glycogen defined as following: large branched polysaccharide consisting of glucose residues; the major carbohydrate reserve of animals, stored primarily in liver and muscle, synthesized and degraded for energy as demanded.. amino acid substitutions defined as following: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.. muscle defined as following: Contractile tissue that produces movement in animals.. alpha-1,4-glucosidase defined as following: An enzyme that catalyzes the hydrolysis of terminal 1,4-linked alpha-D-glucose residues successively from non-reducing ends of polysaccharide chains with the release of beta-glucose. It is also able to hydrolyze 1,6-alpha-glucosidic bonds when the next bond in sequence is 1,4.. glycogenosis defined as following: An autosomal recessive disease in which gene expression of glucose-6-phosphatase is absent, resulting in hypoglycemia due to lack of glucose production. Accumulation of glycogen in liver and kidney leads to organomegaly, particularly massive hepatomegaly. Increased concentrations of lactic acid and hyperlipidemia appear in the plasma. Clinical gout often appears in early childhood.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. lysosome defined as following: A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed).. ERT defined as following: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, DYSPAREUNIA, and progressive development of OSTEOPOROSIS. This may also include the use of progestational agents in combination therapy.. cardiomyopathy defined as following: A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).. Pompe disease defined as following: Glycogen storage disease due to acid maltase deficiency (AMD) is an autosomal recessive trait leading to metabolic myopathy that affects cardiac and respiratory muscles in addition to skeletal muscle and other tissues. AMD represents a wide spectrum of clinical presentations caused by an accumulation of glycogen in lysosomes.. mutant defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. myopathy defined as following: Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.. AAG defined as following: An antineoplastic antibiotic that is structurally similar to the benzoquinone ansamycin antibiotic geldanamycin. A geldanamycin analogue binds to HSP90, a chaperone protein that aids in the assembly, maturation, and folding of proteins. Subsequently, the function of HSP90 is inhibited, leading to the degradation and depletion of client proteins such as kinases and transcription factors involved with cell cycle regulation and signal transduction.. GAA defined as following: A Niger-Congo Kwa language spoken in the capital area of Ghana.. death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. respiratory insufficiency defined as following: Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed). glycogen storage disease II defined as following: An autosomal recessive metabolic disorder due to deficient expression of amylo-1,6-glucosidase (one part of the glycogen debranching enzyme system). The clinical course of the disease is similar to that of glycogen storage disease type I, but milder. Massive hepatomegaly, which is present in young children, diminishes and occasionally disappears with age. Levels of glycogen with short outer branches are elevated in muscle, liver, and erythrocytes. Six subgroups have been identified, with subgroups Type IIIa and Type IIIb being the most prevalent.. gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. human defined as following: Members of the species Homo sapiens..", "label": "yes"} {"id": "converted_995", "sentence1": "Is Growth factor independence 1b (GFI1B) important for hematopoiesis?", "sentence2": "Growth Factor Independence (Gfi) transcription factors play essential roles in hematopoiesis, differentially activating and repressing transcriptional programs required for hematopoietic stem/progenitor cell (HSPC) development and lineage specification, gfi1aa and gfi1b have distinct roles in regulating primitive and definitive hematopoietic progenitors,, gfi1b is required for definitive hematopoiesis, LSD1-kd was associated with the upregulation of key hematopoietic genes, including Gfi1b, GFI1 and GFI1B control the loss of endothelial identity of hemogenic endothelium during hematopoietic commitment, Taken together, our findings demonstrate a critical and specific role of the GFI1 transcription factors in the first steps of the process leading to the generation of hematopoietic progenitors from hemogenic endothelium, A short Gfi-1B isoform controls erythroid differentiation, Gfi-1B is a transcriptional repressor essential for the regulation of erythropoiesis and megakaryopoiesis, Among the few down-regulated genes was Gfi1b, a known repressor of erythroid differentiation, This reversible modulation of endothelial-haematopoietic state is accomplished by targeting key haematopoietic transcription factors for downregulation, including Runx1, Gata1, Gfi1B, Ikaros, and PU.1, Gfi1 and Gfi1b: key regulators of hematopoiesis, we review how Gfi1 and its paralogue Gfi1b control the development of blood cells, discuss how changes in Gfi1 and Gfi1b function contribute to hematological disease and report on the molecular function of these proteins., Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-beta signaling at the bipotent erythro-megakaryocytic progenitor stage, Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis, Targeted gene disruption of GFI1B in mice leads to embryonic lethality resulting from failure to produce definitive erythrocytes, hindering the study of Gfi-1B function in adult hematopoiesis, We here show that, in humans, Gfi-1B controls the development of erythrocytes and megakaryocytes by regulating the proliferation and differentiation of bipotent erythro-megakaryocytic progenitors, To date, we have identified two common integration sites involving genes encoding transcription factors that play a critical role in hematopoiesis (Evi1 and Gfi1b loci), Transcription factors play essential roles in both normal and malignant hematopoiesis. This is the case for the growth factor independent 1b (GFI1B) transcription factor, which is required for erythroid and megakaryocytic differentiation and over-expressed in leukemic patients and cell lines, We localized several conserved non-coding elements containing multiple erythroid specific transcription factor binding sites at the GFI1B locus. In GFI1B-expressing cells a subset of these conserved non-coding elements and the promoter adopt a close spatial conformation, localize with open chromatin sites, harbor chromatin modifications associated with gene activation and bind multiple transcription factors and co-repressors, Our findings indicate that GFI1B regulatory elements behave as activators and repressors, To investigate the molecular effects of growth factor independence 1B (Gfi-1B), a transcription factor essential for the development of hematopoietic cells and differentiation of erythroid and megakaryocytic lineages, Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations, Gfi-1 and Gfi-1b are homologous transcriptional repressors involved in diverse developmental contexts, including hematopoiesis and oncogenesis, Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression pattern of Gfi1b during hematopoiesis that is largely complementary to Gfi1, We found highly dynamic expression patterns of Gfi1b in erythroid cells, megakaryocytes, and their progenitor cells (MEPS) where Gfi1 is not detected. Vice versa, Gfi1b could not be found in granulocytes, activated macrophages, or their granulomonocytic precursors (GMPs) or in mature naive or activated lymphocytes where Gfi1 is expressed, suggesting a complementary regulation of both loci during hematopoiesis, Gfi1 and Gfi1b act equivalently in haematopoiesis, our findings show that an intact SNAG domain is essential for all functions of Gfi1 and that Gfi1b can replace Gfi1 functionally in haematopoiesis, Gfi-1 oncoproteins in hematopoiesis, Recent gene targeting experiments and mutational screening in humans have revealed an essential role for Gfi-1 and Gfi-1B in hematopoiesis, Gfi-1B disruption is embryonic lethal due to a block of erythropoiesis. Gfi-1B is required for both erythroid and megakaryocyte development, Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis, we identified that the expression of Gfi-1B (growth factor independence-1B) is highly restricted to hematopoietic stem cells, erythroblasts, and megakaryocytes, These findings establish Gfi-1B as a novel erythroid regulator and reveal its specific involvement in the regulation of erythroid cell growth through modulating erythroid-specific gene expression, The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages, we establish that Gfi-1b is required for the development of two related blood lineages, erythroid and megakaryocytic, in mice, Gfi-1b(-/-) embryonic stem cells fail to contribute to red cells of adult chimeras. Gfi-1b(-/-) embryos exhibit delayed maturation of primitive erythrocytes and subsequently die with failure to produce definitive enucleated erythrocytes, Gfi-1b is an essential transcriptional regulator of erythroid and megakaryocyte development, Growth factor independence 1b (GFI1B) is a DNA binding repressor of transcription with vital functions in hematopoiesis., Conversely, loss of gfi1b silences runx-1, c-myb, ikaros and cd41, indicating that gfi1b is required for definitive hematopoiesis., Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression pattern of Gfi1b during hematopoiesis that is largely complementary to Gfi1., Gfi1 and Gfi1b: key regulators of hematopoiesis., We show that gfi1aa and gfi1b are expressed in the primitive and definitive sites of hematopoiesis in zebrafish., Targeted gene disruption of GFI1B in mice leads to embryonic lethality resulting from failure to produce definitive erythrocytes, hindering the study of Gfi-1B function in adult hematopoiesis., Growth factor independence 1b (gfi1b) is important for the maturation of erythroid cells and the regulation of embryonic globin expression., Growth factor-independence 1b (Gfi1b) is a zinc finger transcription factor essential for erythroid and megakaryocytic development., Gfi1b (growth factor independence 1b) is a zinc finger transcription factor essential for development of the erythroid and megakaryocytic lineages., In fact, we demonstrate that VPA treatment is able to induce the expression of growth factor-independent protein 1B (GFI1B) and of mixed-lineage leukemia translocated to chromosome 3 protein (MLLT3), which are crucial regulators of erythrocyte and megakaryocyte differentiation, and that the up-regulation of these genes is mediated by the histone hyperacetylation at their promoter sites., Growth factor independence-1B (Gfi-1B) is a transcriptional repressor essential for erythropoiesis and megakaryopoiesis., Gfi-1B (growth factor independence-1B) gene is an erythroid-specific transcription factor, whose expression plays an essential role in erythropoiesis., Evidence that growth factor independence 1b regulates dormancy and peripheral blood mobilization of hematopoietic stem cells., We report here that adult mice conditionally deficient for the transcription Growth factor independence 1b (Gfi1b) show a significant expansion of functional HSCs in the bone marrow and blood., Growth factor-independence 1b (Gfi1b) is a zinc finger transcription factor essential for erythroid and megakaryocytic development, Teleost growth factor independence (gfi) genes differentially regulate successive waves of hematopoiesis., Gfi-1B (growth factor independence-1B) gene is an erythroid-specific transcription factor, whose expression plays an essential role in erythropoiesis, Our data indicate that Gfi-1B signalling is important for commitment and maturation of hematopoietic cell populations., We report here that adult mice conditionally deficient for the transcription Growth factor independence 1b (Gfi1b) show a significant expansion of functional HSCs in the bone marrow and blood[SEP]Relations: GFI1B has relations: cellcomp_protein with nucleus, cellcomp_protein with nucleus, protein_protein with EFEMP2, protein_protein with EFEMP2, protein_protein with PSMA3, protein_protein with PSMA3, bioprocess_protein with regulation of hemopoiesis, bioprocess_protein with regulation of hemopoiesis, protein_protein with CENPB, protein_protein with CENPB. Definitions: GFI1 defined as following: Zinc finger protein Gfi-1 (422 aa, ~45 kDa) is encoded by the human GFI1 gene. This protein is involved in hematopoiesis.. PU.1 defined as following: The human SPI1 wild-type allele is located in the vicinity of 11p11.2 and is approximately 24 kb in length. This allele, which encodes transcription factor PU.1 protein, is involved in the activation of transcription by RNA polymerase II.. megakaryocytes defined as following: Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.. c-myb defined as following: Human MYB wild-type allele is located within 6q22-q23 and is approximately 38 kb in length. This allele, which encodes Myb proto-oncogene protein, plays a role in both the modulation of transcription by RNA polymerase II and differentiation of hematopoietic progenitor cells.. GFI1B defined as following: Human GFI1B wild-type allele is located in the vicinity of 9q34.13 and is approximately 46 kb in length. This allele, which encodes growth factor independent protein 1B, may play a role in the modulation of transcription by RNA polymerase II.. co-repressors defined as following: A subclass of repressor proteins that do not directly bind DNA. Instead, co-repressors generally act via their interaction with DNA-BINDING PROTEINS such as a TRANSCRIPTIONAL SILENCING FACTORS or NUCLEAR RECEPTORS.. zebrafish defined as following: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research.. lineage defined as following: Descent in a line from a common progenitor or source.. blood cells defined as following: The cells found in the body fluid circulating throughout the CARDIOVASCULAR SYSTEM.. Ikaros defined as following: This gene is involved in B-cell and T-cell maturation.. hematological disease defined as following: Disorders of the blood and blood forming tissues.. erythroid cells defined as following: The series of cells in the red blood cell lineage at various stages of differentiation.. Transcription factors defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. erythroid defined as following: 1) Reddish in color. 2) relating to erythrocytes or their precursors.. Evi1 defined as following: Human MECOM wild-type allele is located in the vicinity of 3q26.2 and is approximately 580 kb in length. This allele, which encodes histone-lysine N-methyltransferase MECOM protein, is involved in DNA binding, transcription factor activity and histone methylation. Mutation of the gene is associated with radioulnar synostosis with amegakaryocytic thrombocytopenia-2. Chromosomal translocations involving this gene are associated with leukemogenesis.. cd41 defined as following: Platelet membrane glycoprotein IIb is an integrin alpha subunit that heterodimerizes with INTEGRIN BETA3 to form PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX. It is synthesized as a single polypeptide chain which is then postranslationally cleaved and processed into two disulfide-linked subunits of approximately 18 and 110 kDa in size.. hematopoietic stem cells defined as following: Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood.. Runx1 defined as following: Runt-related transcription factor 1 (453 aa, ~49 kDa) is encoded by the human RUNX1 gene. This protein is involved in the promotion of gene transcription and hematopoiesis.. transcriptional repressor defined as following: Transcription Repressor/Corepressor Gene encodes Transcriptional Repressor/Corepressor, proteins that can regulate transcription by binding to the operator and causing repression. (from Glick: Glossary of Biochemistry and Molecular Biology). VPA defined as following: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. MLLT3 defined as following: Human MLLT3 wild-type allele is located in the vicinity of 9p22 and is approximately 281 kb in length. This allele, which encodes protein AF-9, plays a role in modulation of transcription by RNA polymerase II (Gene Ontology/GO). Acute nonlymphocytic leukemia is associated with the translocation t(9;11)(p22;q23) of this gene and the MLL gene.. red cells defined as following: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.. promoter defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. Growth factor-independence 1b defined as following: This gene plays a role in transcriptional regulation and erythroid cell growth. Translocations in the gene are associated with chronic myeloid leukemia.. cell lines defined as following: Established cell cultures that have the potential to propagate indefinitely.. Gata1 defined as following: Human GATA1 wild-type allele is located in the vicinity of Xp11.23 and is approximately 8 kb in length. This allele, which encodes erythroid transcription factor protein, is involved in the regulation of both transcription by RNA polymerase II and erythroid development.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. progenitor cells defined as following: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.. Gfi-1 defined as following: Human GFI1 wild-type allele is located in the vicinity of 1p22.1 and is approximately 14 kb in length. This allele, which encodes zinc finger protein Gfi-1, plays a role in transcriptional repression during multilineage blood cell development. Mutation of the gene is associated with autosomal recessive severe congenital neutropenia 2 (SCN2) and adult nonimmune chronic idiopathic neutropenia.. endothelial defined as following: A layer of epithelium that lines the heart, blood vessels (ENDOTHELIUM, VASCULAR), lymph vessels (ENDOTHELIUM, LYMPHATIC), and the serous cavities of the body.. hematopoiesis defined as following: The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY).. humans defined as following: Members of the species Homo sapiens.. erythroblasts defined as following: Immature, nucleated ERYTHROCYTES occupying the stage of ERYTHROPOIESIS that follows formation of ERYTHROID PRECURSOR CELLS and precedes formation of RETICULOCYTES. The normal series is called normoblasts. Cells called MEGALOBLASTS are a pathologic series of erythroblasts..", "label": "yes"} {"id": "converted_3744", "sentence1": "Has tocilizumab been assessed against Covid-19?", "sentence2": "Preliminary clinical results have indicated that antagonism of the IL-6 receptor (IL-6R), including with the FDA-approved humanized monoclonal antibody tocilizumab, can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile.[SEP]Relations: interleukin-6 receptor activity has relations: molfunc_protein with IL6ST, molfunc_protein with IL6ST, molfunc_protein with IL6R, molfunc_protein with IL6R. interleukin-6 receptor complex has relations: cellcomp_protein with IL6ST, cellcomp_protein with IL6ST, cellcomp_protein with IL6R, cellcomp_protein with IL6R, cellcomp_protein with IL6, cellcomp_protein with IL6. Definitions: IL-6 receptor defined as following: Cell surface receptors that are specific for INTERLEUKIN-6. They are present on T-LYMPHOCYTES, mitogen-activated B-LYMPHOCYTES, and peripheral MONOCYTES. The receptors are heterodimers of the INTERLEUKIN-6 RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR GP130.. IL-6R defined as following: Combining with interleukin-6 and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. [GOC:jl, GOC:signaling]. tocilizumab defined as following: A recombinant, humanized IgG1 monoclonal antibody directed against the interleukin-6 receptor (IL-6R) with immunosuppressant activity. Tocilizumab targets and binds to both the soluble form of IL-6R (sIL-6R) and the membrane-bound form (mIL-6R), thereby blocking the binding of IL-6 to its receptor. This prevents IL-6-mediated signaling. IL-6, a pro-inflammatory cytokine that plays an important role in the regulation of the immune response, is overproduced in autoimmune disorders, certain types of cancers and possibly various other inflammatory conditions..", "label": "yes"} {"id": "converted_4428", "sentence1": "Is there a dependence between chromatin organization and dorsoventral gene expression in Drosophila?", "sentence2": "Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning., Here, using the dorsoventral patterning of the Drosophila melanogaster embryo as a model system, we provide evidence for the independence of chromatin organization and dorsoventral gene expression. We define tissue-specific enhancers and link them to expression patterns using single-cell RNA-seq. Surprisingly, despite tissue-specific chromatin states and gene expression, chromatin organization is largely maintained across tissues. Our results indicate that tissue-specific chromatin conformation is not necessary for tissue-specific gene expression but rather acts as a scaffold facilitating gene expression when enhancers become active.[SEP]Relations: bone tissue has relations: anatomy_anatomy with endochondral bone tissue, anatomy_anatomy with endochondral bone tissue, anatomy_anatomy with trabecular bone tissue, anatomy_anatomy with trabecular bone tissue, anatomy_anatomy with intramembranous bone tissue, anatomy_anatomy with intramembranous bone tissue, anatomy_anatomy with lamellar bone, anatomy_anatomy with lamellar bone, anatomy_anatomy with osteoid, anatomy_anatomy with osteoid. Definitions: tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. Drosophila defined as following: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology..", "label": "no"} {"id": "converted_292", "sentence1": "Is RET the major gene involved in Hirschsprung disease?", "sentence2": "The RET proto-oncogene is the major gene associated to HSCR with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology, The RET proto-oncogene is the major gene for HSCR with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology, The rearranged during transfection gene (RET) is considered the major gene in HSCR, RET is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology, While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease, The rearranged during transfection (RET) proto-oncogene is the major susceptibility gene for Hirschsprung disease, and germline mutations in RET have been reported in up to 50% of the inherited forms of Hirschsprung disease and in 15-20% of sporadic cases of Hirschsprung disease., The RET proto-oncogene is the major gene involved in the complex genetics of Hirschsprung disease (HSCR), or aganglionic megacolon, showing causative loss-of-function mutations in 15-30% of the sporadic cases., The major gene for Hirschsprung disease (HSCR) encodes the receptor tyrosine kinase RET., The RET proto-oncogene is considered to be the major susceptibility gene involved in Hirschsprung disease., Hirschsprung disease (HSCR), a developmental disorder characterized by the absence of enteric neurons in distal segments of the gut, shows a complex pattern of inheritance, with the RET protooncogene acting as a major gene and additional susceptibility loci playing minor roles., Traditional RET germline mutations account for a small subset of Hirschsprung disease patients, but several studies have shown that there is a specific haplotype of RET associated with the sporadic forms of Hirschsprung disease., PURPOSE: The RET proto-oncogene is considered to be the major susceptibility gene involved in Hirschsprung disease., The RET proto-oncogene is the major gene involved in the pathogenesis of Hirschsprung (HSCR), a complex genetic disease characterized by lack of ganglia along variable lengths of the gut., While rare variants (RVs) in the coding sequence (CDS) of several genes involved in ENS development lead to disease, the association of common variants (CVs) with HSCR has only been reported for RET (the major HSCR gene) and NRG1., The rearranged during transfection (RET) proto-oncogene is the major susceptibility gene for Hirschsprung disease, and germline mutations in RET have been reported in up to 50% of the inherited forms of Hirschsprung disease and in 15-20% of sporadic cases of Hirschsprung disease., The major gene for Hirschsprung disease (HSCR) encodes the receptor tyrosine kinase RET. In a study of 690 European- and 192 Chinese-descent probands and their parents or controls, we demonstrate the ubiquity of a >4-fold susceptibility from a C-->T allele (rs2435357: p = 3.9 x 10(-43) in European ancestry; p = 1.1 x 10(-21) in Chinese samples) that probably arose once within the intronic RET enhancer MCS+9.7., Hirschsprung disease (HSCR), a developmental disorder characterized by the absence of enteric neurons in distal segments of the gut, shows a complex pattern of inheritance, with the RET protooncogene acting as a major gene and additional susceptibility loci playing minor roles., BACKGROUND: The RET gene encodes a tyrosine kinase receptor involved in different human neurocristopathies, such as specific neuroendocrine tumours and Hirschsprung disease (HSCR)., The first major susceptibility gene for Hirschsprung disease is the RET proto-oncogene on 10q11.2., The developmental abnormalities apparent in these mice, together with the observation that the major tissues affected in MEN 2 and Hirschsprung disease have a common origin in the embryonal neural crest, suggest that RET encodes a receptor for a developmental regulator involved in the genesis of a variety of neural crest derivatives, and in the organogenesis of the kidney., RET is the major gene involved in HSCR., Recent advances show that the RET gene is a major locus involved in the pathogenesis of HSCR., Although with several genes involved in its pathogenesis, the major HSCR gene is the RET proto-oncogene., In this model, a major gene, RET, is involved in most if not all cases of isolated (i.e., nonsyndromic) HSCR, in conjunction with other autosomal susceptibility loci under a multiplicative model., The RET proto-oncogene is the major gene involved in the pathogenesis of Hirschsprung (HSCR), a complex genetic disease characterized by lack of ganglia along variable lengths of the gut, The RET proto-oncogene is the major gene involved in the complex genetics of Hirschsprung disease (HSCR), or aganglionic megacolon, showing causative loss-of-function mutations in 15-30% of the sporadic cases, The RET proto-oncogene is considered to be the major susceptibility gene involved in Hirschsprung disease, Analysis of the RET gene, the major gene involved in HSCR susceptibility, revealed neither linkage nor mutations, RET is the major gene involved in HSCR, Although with several genes involved in its pathogenesis, the major HSCR gene is the RET proto-oncogene, While rare variants (RVs) in the coding sequence (CDS) of several genes involved in ENS development lead to disease, the association of common variants (CVs) with HSCR has only been reported for RET (the major HSCR gene) and NRG1, The rearranged during transfection (RET) proto-oncogene is the major susceptibility gene for Hirschsprung disease, and germline mutations in RET have been reported in up to 50% of the inherited forms of Hirschsprung disease and in 15-20% of sporadic cases of Hirschsprung disease, Recent advances show that the RET gene is a major locus involved in the pathogenesis of HSCR, In this model, a major gene, RET, is involved in most if not all cases of isolated (i.e., nonsyndromic) HSCR, in conjunction with other autosomal susceptibility loci under a multiplicative model, We report on mutation analysis of five genes involved in the receptor tyrosine kinase (RET) or the endothelin-signalling pathways in 28 sporadic Japanese patients with Hirschsprung disease, In addition to mutations in the RET and EDNRB genes, embryonic environmental factors and/or other genetic factors appear to be involved in the development of Hirschsprung disease, The RET gene is the major HSCR gene, although reduced penetrance of RET mutations and variable expression of HSCR phenotype indicates that more than one gene is required[SEP]Relations: hirschsprung disease, susceptibility to has relations: disease_protein with RET, disease_protein with RET, disease_protein with COMT, disease_protein with COMT, disease_protein with EDNRB, disease_protein with EDNRB, disease_protein with MED12, disease_protein with MED12, disease_disease with Hirschsprung disease, disease_disease with Hirschsprung disease. Definitions: coding sequence defined as following: A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).. neuroendocrine tumours defined as following: Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via APUD CELLS), the presence of tumor-associated antigens, and isozyme composition.. variant defined as following: An alteration or difference from a norm or standard.. receptor tyrosine kinase defined as following: High affinity nerve growth factor receptor (796 aa, ~87 kDa) is encoded by the human NTRK1 gene. This protein is involved in tyrosine phosphorylation, axonogenesis and receptor-mediated signaling.. RET gene defined as following: This gene plays an essential role in neural crest development, cellular growth and differentiation. Mutations in the gene are associated with a variety of neoplasias and carcinomas.. ganglia defined as following: Clusters of multipolar neurons surrounded by a capsule of loosely organized CONNECTIVE TISSUE located outside the CENTRAL NERVOUS SYSTEM.. RET defined as following: a unit of radiation dose. enhancer element defined as following: Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.. EDNRB defined as following: Endothelin receptor type B (442 aa, ~50 kDa) is encoded by the human EDNRB gene. This protein is involved in vasoconstriction and vasodilation.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. proto-oncogene defined as following: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.. CDS defined as following: Neutral lipid storage disease (NLSD) refers to a group of diseases characterized by a deficit in the degradation of cytoplasmic triglycerides and their accumulation in cytoplasmic lipid vacuoles in most tissues of the body. The group is heterogeneous: currently cases of NLSD with icthyosis (NLSDI/Dorfman-Chanarin disease; see this term) and NLSD with myopathy (NLSDM/neutral lipid storage myopathy; see this term) can be distinguished.. NRG1 defined as following: Neuregulin-1 (222 aa, ~24 kDa) is encoded by the human NRG1 gene. This protein is involved in binding to receptors from the EGF receptor family of protein tyrosine kinases.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. locus defined as following: The position of a gene or a chromosomal marker on a chromosome; also, a stretch of DNA at a particular place on a particular chromosome. The use of locus is sometimes restricted to mean regions of DNA that are expressed.. human defined as following: Members of the species Homo sapiens.. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. MEN 2 defined as following: A form of multiple endocrine neoplasia characterized by the presence of medullary carcinoma (CARCINOMA, MEDULLARY) of the THYROID GLAND, and usually with the co-occurrence of PHEOCHROMOCYTOMA, producing CALCITONIN and ADRENALINE, respectively. Less frequently, it can occur with hyperplasia or adenoma of the PARATHYROID GLANDS. This disease is due to gain-of-function mutations of the MEN2 gene on CHROMOSOME 10 (Locus: 10q11.2), also known as the RET proto-oncogene that encodes a RECEPTOR PROTEIN-TYROSINE KINASE. It is an autosomal dominant inherited disease.. gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"} {"id": "converted_437", "sentence1": "Is there a role for the cylindromatosis tumor suppressor (CYLD) in lung cancer?", "sentence2": "Over-expressing CYLD augments antitumor activity of TRAIL by inhibiting the NF-κB survival signaling in lung cancer cells, increased expression of CYLD directly blocks TRAIL-induced NF-κB activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. CYLD may act as a therapeutic target of lung cancer. Targeting CYLD, in combination with TRAIL, may be a new strategy to treat lung cancer with high NF-κB activity, Truncation of the catalytic domain of the cylindromatosis tumor suppressor impairs lung maturation, down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer, Deletion of exon 9 would cause a carboxyl-terminal truncation of CYLD and inactivation of its deubiquitinating activity. In accordance with previous studies, fibroblasts from Cyld(Delta 9/Delta 9) embryos had hyperactive nuclear factor kappaB and c-Jun kinase pathways compared with control fibroblasts. Cyld(Delta 9/Delta 9) newborn mice were smaller than wild-type littermates with a short and kinky tail and no major developmental defects. However, Cyld(Delta 9/Delta 9) mice died shortly after birth from apparent respiratory dysfunction. Histological examination of E18.5 Cyld(Delta 9/Delta 9) lungs demonstrated an immature phenotype characterized by hyperplasic mesenchyme but apparently normal epithelial, smooth muscle. and endothelial structures. Our study identifies an important role of CYLD in lung maturation, which may underlie the development of many cases of lung cancer, Mutations that truncate and inactivate the carboxyl-terminal deubiquitinating domain of CYLD underlie the development of skin appendage tumors in humans, whereas down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer., Our study identifies an important role of CYLD in lung maturation, which may underlie the development of many cases of lung cancer., Mutations that truncate and inactivate the carboxyl-terminal deubiquitinating domain of CYLD underlie the development of skin appendage tumors in humans, whereas down-regulation of Cyld expression has been associated with the development of various types of human malignancies including lung cancer[SEP]Relations: lung has relations: anatomy_protein_present with CYLD, anatomy_protein_present with CYLD, anatomy_protein_present with PDGFRA, anatomy_protein_present with PDGFRA, anatomy_protein_present with MKRN2OS, anatomy_protein_present with MKRN2OS, anatomy_protein_present with NCOR2, anatomy_protein_present with NCOR2, anatomy_protein_present with CYSLTR2, anatomy_protein_present with CYSLTR2. Definitions: catalytic domain defined as following: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.. respiratory dysfunction defined as following:When you're short of breath, it's hard or uncomfortable for you to take in the oxygen your body needs. You may feel as if you're not getting enough air. Sometimes you can have mild breathing problems because of a stuffy nose or intense exercise. But shortness of breath can also be a sign of a serious disease.
Many conditions can make you feel short of breath:
If you often have trouble breathing, it is important to find out the cause.
. humans defined as following: Members of the species Homo sapiens.. smooth muscle defined as following: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed). CYLD defined as following: Ubiquitin carboxyl-terminal hydrolase CYLD (956 aa, ~107 kDa) is encoded by the human CYLD gene. This protein is involved in the mediation of protein deubiquitination and the regulation of the cell cycle.. TRAIL defined as following: Human TNFSF10 wild-type allele is located within 3q26 and is approximately 18 kb in length. This allele, which encodes tumor necrosis factor ligand superfamily member 10 protein, is involved in the induction and modulation of apoptosis.. lungs defined as following: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.. epithelial defined as following: A term that refers to the cells that make up the epithelial tissues. They are found in the skin, and in the parenchyma, surface and lumen of internal organs.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"} {"id": "converted_4543", "sentence1": "Is CircRNA produced by back splicing of exon, intron or both, forming exon or intron circRNA?", "sentence2": "CircRNAs are a subclass of lncRNAs that have been found to be abundantly present in a wide range of species, including humans. CircRNAs are generally produced by a noncanonical splicing event called backsplicing that is dependent on the canonical splicing machinery, giving rise to circRNAs classified into three main categories: exonic circRNA, circular intronic RNA, and exon-intron circular RNA. , Circular RNA (circRNA) is a large class of covalently closed circRNA., Human transcriptome contains a large number of circular RNAs (circRNAs) that are mainly produced by back splicing of pre-mRNA., Analyses of the other reads revealed two origins for non-canonical circRNAs: (1) Intronic sequences for lariat-derived intronic circRNAs and intron circles, (2) Mono-exonic genes (mostly non-coding) for either a new type of circRNA (including only part of the exon: sub-exonic circRNAs) or, even more rarely, mono-exonic canonical circRNAs., Our objective was to characterize non-canonical circRNAs, namely not originating from back splicing and circRNA produced by non-coding genes., Recent studies have identified a new class of ncRNAs called circular RNAs (circRNAs), which are produced by back-splicing and fusion of either exons, introns, or both exon-intron into covalently closed loops., CircRNA is produced by the reverse splicing of exon, intron or both, forming exon or intron circRNA., Circular RNAs (circRNAs) belong to a recently re-discovered species of RNA that emerge during RNA maturation through a process called back-splicing. , Exonic circular RNAs (circRNAs) are RNA molecules that are covalently closed by back-splicing via canonical splicing machinery. , Human transcriptome contains a large number of circular RNAs (circRNAs) that are mainly produced by back splicing of pre-mRNA. , Circular RNAs (circRNAs) are a class of non‑coding RNAs formed by covalently closed loops through back‑splicing and exon‑skipping. , Here, we review the emerging understanding that both, circRNAs produced by co- and posttranscriptional head-to-tail \"backsplicing\" of a downstream splice donor to a more upstream splice acceptor, as well as circRNAs generated from intronic lariats during colinear splicing, may exhibit physiologically relevant regulatory functions in eukaryotes., Compared to the linear RNA, circRNAs are produced differentially by backsplicing exons or lariat introns from a pre-messenger RNA (mRNA) forming a covalently closed loop structure missing 3' poly-(A) tail or 5' cap, rendering them immune to exonuclease-mediated degradation., CircRNAs are a large class of endogenous single-stranded RNA that is different from other linear RNA, which are produced by back-splicing and fusion of either exons, introns, or both exon-intron into covalently closed loops., Circular RNAs (circRNAs) derived from back-spliced exons have been widely identified as being co-expressed with their linear counterparts.[SEP]Relations: Viral Messenger RNA Synthesis has relations: pathway_protein with POLR2C, pathway_protein with POLR2C, pathway_protein with POLR2B, pathway_protein with POLR2B, pathway_protein with POLR2K, pathway_protein with POLR2K, pathway_protein with POLR2E, pathway_protein with POLR2E, pathway_protein with POLR2L, pathway_protein with POLR2L. Definitions: circular RNAs defined as following: RNA molecules in which the 3' and 5' ends are covalently joined to form a closed continuous loop. They are resistant to digestion by EXORIBONUCLEASES.. RNA defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). pre-mRNA defined as following: A primary RNA transcript synthesized from a DNA template in eukaryotic nuclei which is post-transcriptionally modified and spliced to produce a mature mRNA.. humans defined as following: Members of the species Homo sapiens.. exons defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.. eukaryotes defined as following: Organism or cells with a nucleus separated from the cytoplasm by a two membrance nuclear envelope and compartmentalization of function into distinct cytoplasmic organelles.. introns defined as following: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.. exon defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.. intron defined as following: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes..", "label": "yes"} {"id": "converted_2799", "sentence1": "Can simvastatin alleviate depressive symptoms?", "sentence2": "Simvastatin-treated patients experienced significantly more reductions in HDRS scores compared to the placebo group by the end of the trial (p=0.02). Early improvement and response rates were significantly greater in the simvastatin group than the placebo group (p=0.02 and p=0.01, respectively) but remission rate was not significantly different between the two groups (p=0.36)., In conclusion, simvastatin seems to be a safe and effective adjuvant therapy for patients suffering from major depressive disorder.[SEP]Relations: Simvastatin has relations: drug_effect with Anxiety, drug_effect with Anxiety, drug_effect with Pain, drug_effect with Pain, drug_effect with Headache, drug_effect with Headache, drug_effect with Arthritis, drug_effect with Arthritis, drug_effect with Dyspnea, drug_effect with Dyspnea. Definitions: simvastatin defined as following: A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL..", "label": "yes"} {"id": "converted_1285", "sentence1": "Are EDNRB mutations involved in the development of Hirschsprung disease?", "sentence2": "QTL analysis identifies a modifier locus of aganglionosis in the rat model of Hirschsprung disease carrying Ednrb(sl) mutations, As reported previously, when the same null mutation of the Ednrb gene, Ednrb(sl), was introgressed into the F344 strain, almost 60% of F344-Ednrb(sl/sl) pups did not show any symptoms of aganglionosis, appearing healthy and normally fertile., Genetic background strongly modifies the severity of symptoms of Hirschsprung disease, but not hearing loss in rats carrying Ednrb(sl) mutations, In this study, we found that the null mutation of the Ednrb gene, thought indispensable for enteric neuron development, is insufficient to result in HSCR disease when bred onto a different genetic background in rats carrying Ednrb(sl) mutations., New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease., The aim of this study was to evaluate the implication of the EDN3 and EDNRB genes in a series of patients with Hirschsprung disease from Spain and determinate their mutational spectrum., A De Novo novel mutation of the EDNRB gene in a Taiwanese boy with Hirschsprung disease, Although mutations in eight different genes (EDNRB, EDN3, ECE1, SOX10, RET, GDNF, NTN, SIP1) have been identified in affected individuals, it is now clear that RET and EDNRB are the primary genes implicated in the etiology of HSCR., Mutations in genes of the RET receptor tyrosine kinase and endothelin receptor B (EDNRB) signaling pathways have been shown to be associated in HSCR patients. , Interactions between Sox10 and EdnrB modulate penetrance and severity of aganglionosis in the Sox10Dom mouse model of Hirschsprung disease, Molecular genetic analyses have revealed that interactions between mutations in the genes encoding the RET receptor tyrosine kinase and the endothelin receptor type B (EDNRB) are central to the genesis of HSCR, Genome-wide association study and mouse model identify interaction between RET and EDNRB pathways in Hirschsprung disease, Thus, genetic interaction between mutations in RET and EDNRB is an underlying mechanism for this complex disorder., EDNRB/EDN3 and Hirschsprung disease type II., Analysis of the RET, GDNF, EDN3, and EDNRB genes in patients with intestinal neuronal dysplasia and Hirschsprung disease, wo susceptibility genes have been recently identified in HSCR, namely the RET proto-oncogene and the endothelin B receptor (EDNRB) gene., We conclude that Ednrb loss only in neural crest cells is sufficient to produce the Hirschsprungs disease phenotype observed with genomic Ednrb mutations, EDNRB mutations were detected in 2 of the 13 short-segment HD, The mutations of EDNRB gene and EDN-3 gene are found in the short-segment HD of sporadic Hirschsprung's disease in Chinese population, which suggests that the EDNRB gene and EDN-3 gene play important roles in the pathogenesis of HD, Functional characterization of three mutations of the endothelin B receptor gene in patients with Hirschsprung's disease, Hirschsprung's disease (HSCR) is one the most common congenital intestinal disease. It leads to aganglionic megacolon in the early childhood. Several susceptibility genes have been identified : RET protooncogene and its ligand, glial cell derived neutrophic factor (GDNF), Sox 10, Endothelin-3 (EDN3) and its receptor B (EDNRB). EDNRB mutations are found in 5% of familial or sporadic HSCR, Enteric aganglionosis in Hirschsprung disease has been linked to genes coding for endothelin-3 (EDN3) and the endothelin B receptor (EDNRB), To date, three genes have been identified as susceptibility genes for Hirschsprung's disease (HSCR), the RET proto-oncogene, the endothelin-B receptor gene (EDNRB) and the endothelin-3 gene (EDN3), Our data indicate that RET and EDNRB mutations have a role in the aetiology of some sporadically occurring HSCR, Mutations of the endothelin-B receptor and endothelin-3 genes in Hirschsprung's disease, The endothelin-B receptor gene (EDNRB) and the endothelin-3 gene (EDN3) have recently been recognized as susceptibility genes for Hirschsprung's disease (HD), These observations confirm that impaired function of the endothelin-B receptor or endothelin-3 is involved in the aetiology of some human HD cases. EDNRB mutations appear to be associated with short-segment HD, in contrast to RET mutations, which are found mainly in long-segment aganglionosis, In addition to mutations in the RET and EDNRB genes, embryonic environmental factors and/or other genetic factors appear to be involved in the development of Hirschsprung disease., Heterozygous endothelin receptor B (EDNRB) mutations in isolated Hirschsprung disease., QTL analysis identifies a modifier locus of aganglionosis in the rat model of Hirschsprung disease carrying Ednrb(sl) mutations., Homozygous mutations in the endothelin-B receptor gene (EDNRB) on 13q22 have been identified in humans and mice with Hirschsprung disease type 2 (HSCR2)., A De Novo novel mutation of the EDNRB gene in a Taiwanese boy with Hirschsprung disease., Hitherto however, homozygosity for EDNRB mutations accounted for the HSCR-Waardenburg syndrome (WS) association., These data might suggest that EDNRB mutations could be dosage sensitive: heterozygosity would predispose to isolated HSCR with incomplete penetrance, while homozygosity would result in more complex neurocristopathies associating HSCR and WS features., Highly recurrent RET mutations and novel mutations in genes of the receptor tyrosine kinase and endothelin receptor B pathways in Chinese patients with sporadic Hirschsprung disease., Mutations in genes encoding the RET receptor tyrosine kinase and endothelin receptor type B (EDNRB) are involved in HSCR pathogenesis; however, also important in ENS development are molecules that mediate events that are more restricted than those of RET and EDNRB, act later in development and which might not be HSCR-associated., Several missense mutations of the endothelin-B receptor (EDNRB) associated with Hirschsprung disease have recently been identified., These findings indicate that these missense mutations result in loss of function of EDNRB, and may provide the molecular pathological basis of Hirschsprung disease in some individuals., Manifestation of the disease has been linked to mutations in genes that encode the crucial signals for the development of the enteric nervous system-the RET and EDNRB signalling pathways., In addition to mutations in the RET and EDNRB genes, embryonic environmental factors and/or other genetic factors appear to be involved in the development of Hirschsprung disease, In this study, we investigated whether germline mutations of endothelin receptor B (EDNRB), a gene involved in Hirschsprung disease (HSCR), could also predispose for malignant melanoma (MM), However, the similarity between the distal colonic aganglionosis in Hirschsprung disease and that due to EDN3 or EDNRB mutations led to the hypothesis that levels of expression of these genes might be affected in the absence of mutation, thus causing the Hirschsprung disease phenotype, Our data strongly suggest that EDNRB is involved in predisposition for two different multigenic disorders, HSCR and melanoma.[SEP]Relations: EDNRB has relations: disease_protein with Hirschsprung disease, disease_protein with Hirschsprung disease, disease_protein with hirschsprung disease, susceptibility to, disease_protein with hirschsprung disease, susceptibility to. Hirschsprung disease has relations: disease_protein with EDNRB, disease_protein with EDNRB, disease_protein with EDNRB, disease_protein with EDNRB, disease_protein with EDNRB, disease_protein with EDNRB. Definitions: EDNRB defined as following: Endothelin receptor type B (442 aa, ~50 kDa) is encoded by the human EDNRB gene. This protein is involved in vasoconstriction and vasodilation.. receptor tyrosine kinase defined as following: High affinity nerve growth factor receptor (796 aa, ~87 kDa) is encoded by the human NTRK1 gene. This protein is involved in tyrosine phosphorylation, axonogenesis and receptor-mediated signaling.. hearing loss defined as following: Partial or complete loss of the ability to detect or understand sounds resulting from damage to the outer, middle, or inner ear structures. Causes include exposure to loud noise, ear infections, injuries to the ear, genetic, and congenital disorders.. HD defined as following: A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen.. EDN3 defined as following: This gene is involved in vasoconstriction.. Ednrb gene defined as following: This gene is involved in cell signaling.. endothelin-3 defined as following: A 21-amino acid peptide that circulates in the plasma, but its source is not known. Endothelin-3 has been found in high concentrations in the brain and may regulate important functions in neurons and astrocytes, such as proliferation and development. It also is found throughout the gastrointestinal tract and in the lung and kidney. (N Eng J Med 1995;333(6):356-63). malignant melanoma defined as following: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445). RET receptor tyrosine kinase defined as following: Receptor protein-tyrosine kinases involved in the signaling of GLIAL CELL-LINE DERIVED NEUROTROPHIC FACTOR ligands. They contain an extracellular cadherin domain and form a receptor complexes with GDNF RECEPTORS. Mutations in ret protein are responsible for HIRSCHSPRUNG DISEASE and MULTIPLE ENDOCRINE NEOPLASIA TYPE 2.. NTN defined as following: This gene plays a role in both inflammatory processes and cellular adhesion.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. RET defined as following: a unit of radiation dose. MM defined as following: A unit of concentration (molarity unit) equal to one thousandth of a mole (10E-3 mole) of solute per one liter of solution.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. GDNF defined as following: The founding member of the glial cell line-derived neurotrophic factor family. It was originally characterized as a NERVE GROWTH FACTOR promoting the survival of MIDBRAIN dopaminergic NEURONS, and it has been studied as a potential treatment for PARKINSON DISEASE.. Hirschsprung's disease defined as following: Congenital MEGACOLON resulting from the absence of ganglion cells (aganglionosis) in a distal segment of the LARGE INTESTINE. The aganglionic segment is permanently contracted thus causing dilatation proximal to it. In most cases, the aganglionic segment is within the RECTUM and SIGMOID COLON.. glial cell defined as following: The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. melanoma defined as following: A benign or malignant, primary or metastatic neoplasm affecting the melanocytes.. neuron defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. RET proto-oncogene defined as following: This gene plays an essential role in neural crest development, cellular growth and differentiation. Mutations in the gene are associated with a variety of neoplasias and carcinomas.. molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. colonic aganglionosis defined as following: The severe form of Hirschsprung disease, this is characterized by a complete lack of nerve cells in the large intestine, and often a partial lack in the small intestine. The bowel is not stimulated without innervation and obstruction ensues. Surgical intervention is necessary.. neural crest cells defined as following: Neuroectodermal cells of the neural crest. They differentiate into various cell types during EMBRYOGENESIS including craniofacial MESENCHYME; ENDOCRINE CELLS; MELANOCYTES and PERIPHERAL NERVOUS SYSTEM.. locus defined as following: The position of a gene or a chromosomal marker on a chromosome; also, a stretch of DNA at a particular place on a particular chromosome. The use of locus is sometimes restricted to mean regions of DNA that are expressed.. WS defined as following: An autosomal recessive disorder that causes premature aging in adults, characterized by sclerodermal skin changes, cataracts, subcutaneous calcification, muscular atrophy, a tendency to diabetes mellitus, aged appearance of the face, baldness, and a high incidence of neoplastic disease.. humans defined as following: Members of the species Homo sapiens.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"} {"id": "converted_1556", "sentence1": "Is CHEK2 involved in cell cycle control?", "sentence2": "Moreover, cell-cycle progression genes [i.e. E2F transcription factor (E2F) family and histone deacetylase ( HDAC )] and DNA-repair genes [i.e. growth arrest and DNA-damage-inducible, gamma ( GADD45G ) family and serine/threonine-protein kinase Chk2 ( CHEK2)] were also increased., As CHEK2 is a cell-cycle master controller, we tested the hypothesis that heterozygosity for the frameshift alteration CHEK2*1100delC is associated with increased risk of malignant melanoma., In the current study, we evaluated the possible associations of seven common variants of the DNA repair and cell cycle control genes BRCA2 and CHEK2 with malignant melanoma (MM)., Promotor methylation analysis of key regulatory genes involved in cell cycle control (p14, p15, p16, CHK2), DNA repair (hMLH1), apoptosis (p73, survivin, DAPK), and differentiation (RARb, WT1) was performed by methylation-specific polymerase chain reaction., CHEK2 is a key cell cycle control gene encoding a pluripotent kinase that can cause arrest or apoptosis in response to unrepaired DNA damage., High-fidelity maintenance of genomic integrity in eukaryotes is ensured by cell cycle checkpoints and DNA repair. The checkpoint kinase, Chk2, has been implicated in both of these responses. In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation. The fully activated Chk2 then phosphorylates downstream substrates of cell cycle control., Checkpoint kinase 2 (hCHK2/hCds1) is a tumor suppressor gene involved in cell-cycle control.[SEP]Relations: CDKN2A has relations: bioprocess_protein with regulation of cell cycle, bioprocess_protein with regulation of cell cycle, bioprocess_protein with negative regulation of G1/S transition of mitotic cell cycle, bioprocess_protein with negative regulation of G1/S transition of mitotic cell cycle, bioprocess_protein with negative regulation of cell growth, bioprocess_protein with negative regulation of cell growth, bioprocess_protein with negative regulation of cell population proliferation, bioprocess_protein with negative regulation of cell population proliferation, bioprocess_protein with G1/S transition of mitotic cell cycle, bioprocess_protein with G1/S transition of mitotic cell cycle. Definitions: variants defined as following: An alteration or difference from a norm or standard.. RARb defined as following: Human RARB wild-type allele is located within 3p24 and is approximately 170 kb in length. This allele, which encodes retinoic acid receptor beta protein, plays a role in the mediation off cellular signal transduction in embryonic morphogenesis, cell growth and differentiation.. gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. Checkpoint kinase 2 defined as following: Serine/threonine-protein kinase Chk2 (543 aa, ~61 kDa) is encoded by the human CHEK2 gene. This protein plays an essential role in the DNA damage checkpoint of the cell cycle.. p16 defined as following: Human CDKN2A wild-type allele is located in the vicinity of 9p21 and is approximately 27 kb in length. This allele, which encodes both cyclin-dependent kinase inhibitor 2A protein and and tumor suppressor ARF protein, is involved in cell cycle regulation at the G1 phase. The allele is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene.. p73 defined as following: Tumor protein p73 (636 aa, ~70 kDa) is encoded by the human TP73 gene. This protein is involved in the regulation of transcription, DNA damage response and apoptosis.. WT1 defined as following: An embryonal neoplasm characterized by the presence of epithelial, mesenchymal, and blastema components. The vast majority of cases arise from the kidney. A small number of cases with morphologic features resembling Wilms tumor of the kidney have been reported arising from the ovary and the cervix.. tumor suppressor gene defined as following: Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.. MM defined as following: A unit of concentration (molarity unit) equal to one thousandth of a mole (10E-3 mole) of solute per one liter of solution.. BRCA2 defined as following: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. Mutations in this gene predispose humans to breast and ovarian cancer. It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev 2000;14(11):1400-6). DAPK defined as following: This gene is involved in pro-apoptotic regulation.. p15 defined as following: Human CDKN2B wild-type allele is located within 9p21 and is approximately 27 kb in length. This allele, which encodes cyclin-dependent kinase 4 inhibitor B protein, plays roles in both the regulation of cell growth and tumor suppression.. eukaryotes defined as following: Organism or cells with a nucleus separated from the cytoplasm by a two membrance nuclear envelope and compartmentalization of function into distinct cytoplasmic organelles.. malignant melanoma defined as following: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445). arrest defined as following: Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.. p14 defined as following: Tumor suppressor genes located on human chromosome 9 in the region 9p21. This gene is either deleted or mutated in a wide range of malignancies. (From Segen, Current Med Talk, 1995) Two alternatively spliced gene products are encoded by p16: CYCLIN-DEPENDENT KINASE INHIBITOR P16 and TUMOR SUPPRESSOR PROTEIN P14ARF.. hMLH1 defined as following: Human MLH1 wild-type allele is located in the vicinity of 3p21.3 and is approximately 57 kb in length. This allele, which encodes DNA mismatch repair protein Mlh1, plays a role in DNA mismatch repair. Aberrant alleles are associated with colon, endometrial and stomach cancers. Further, the defects in MLH1 are a cause of hereditary non-polyposis colorectal cancer.. survivin defined as following: Human BIRC5 wild-type allele is located in the vicinity of 17q25 and is approximately 10 kb in length. This allele, which encodes baculoviral IAP repeat-containing protein 5, is involved in the prevention of apoptotic cell death.. CHEK2 defined as following: Serine/threonine-protein kinase Chk2 (543 aa, ~61 kDa) is encoded by the human CHEK2 gene. This protein plays an essential role in the DNA damage checkpoint of the cell cycle..", "label": "yes"} {"id": "converted_1699", "sentence1": "Is RIP1 (RIP-1) part of the necrosome?", "sentence2": "formation of a different necrosome whose components, besides RIP1 and RIP3, are still unknown, necrosome complex consisting of RIP1, RIP3, FADD, caspase-8 and cFLIP(L)., assembly of a supramolecular complex containing the receptor-interacting protein kinases 1 and 3 (RIP1 and RIP3) that delivers a pronecrotic signal. Such complex has recently been dubbed necrosome, Receptor interacting protein kinase 1 (RIPK1/RIP1) and RIP3 are key components of the necrosome. , The phosphorylation of RIP1 and RIP3 is critical for assembly of the necrosome,, RIP1-RIP3 \"necrosome\" complex , RIP1 and RIP3 mediate necrosome aggregation leading to the formation of amyloid-like signaling complexes., Formation of the RIP1/RIP3 complex (called necrosome) , The RIP1/RIP3 necrosome , Rip1-Rip3 death complex (necrosome), he 'necrosome', that includes receptor-interacting protein (RIP)1, RIP3 and caspase-8. , RIP-1 kinase activity triggers formation of the necrosome (in complex with RIP-3) leading to programmed necrosis. [SEP]Relations: Protein S human has relations: drug_drug with Cefpirome, drug_drug with Cefpirome, drug_drug with Cefpirome, drug_drug with Cefpirome, drug_drug with Cefpirome, drug_drug with Cefpirome, drug_drug with Interferon alfa-n1, drug_drug with Interferon alfa-n1, drug_drug with Interferon alfa-n1, drug_drug with Interferon alfa-n1. Definitions: RIP-3 defined as following: Receptor-interacting serine/threonine-protein kinase 3 (518 aa, ~57 kDa) is encoded by the human RIPK3 gene. This protein plays a role in the induction of necrosis.. FADD defined as following: FAS-associated death domain protein (208 aa, ~23 kDa) is encoded by the human FADD gene. This protein is involved in the positive regulation of caspase-dependent apoptosis.. caspase-8 defined as following: A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.. RIP3 defined as following: Myosin phosphatase Rho-interacting protein (1025 aa, ~117 kDa) is encoded by the human MPRIP gene. This protein plays a role in the recruitment of myosin phosphatase to the cytoskeleton.. RIP1 defined as following: Receptor-interacting serine/threonine-protein kinase 1 (671 aa, ~76 kDa) is encoded by the human RIPK1 gene. This protein plays a role in signaling that mediates inflammation, serine/threonine phosphorylation and cell death.. supramolecular complex defined as following: A cellular component that consists of an indeterminate number of proteins or macromolecular complexes, organized into a regular, higher-order structure such as a polymer, sheet, network or a fiber. [GOC:dos].", "label": "yes"} {"id": "converted_4052", "sentence1": "Is SLIC-CAGE used for quantification of translation?", "sentence2": "Transcription Start Site Mapping Using Super-low Input Carrier-CAGE., SLIC-CAGE: high-resolution transcription start site mapping using nanogram-levels of total RNA., Cap analysis of gene expression (CAGE) is a methodology for genome-wide quantitative mapping of mRNA 5' ends to precisely capture transcription start sites at a single nucleotide resolution. In combination with high-throughput sequencing, CAGE has revolutionized our understanding of the rules of transcription initiation, led to discovery of new core promoter sequence features, and discovered transcription initiation at enhancers genome-wide. The biggest limitation of CAGE is that even the most recently improved version (nAnT-iCAGE) still requires large amounts of total cellular RNA (5 µg), preventing its application to scarce biological samples such as those from early embryonic development or rare cell types. Here, we present SLIC-CAGE, a Super-Low Input Carrier-CAGE approach to capture 5' ends of RNA polymerase II transcripts from as little as 5-10 ng of total RNA. This dramatic increase in sensitivity is achieved by specially designed, selectively degradable carrier RNA. We demonstrate the ability of SLIC-CAGE to generate data for genome-wide promoterome with 1000-fold less material than required by existing CAGE methods, by generating a complex, high-quality library from mouse embryonic day 11.5 primordial germ cells., Cap analysis of gene expression (CAGE) is a method used for single-nucleotide resolution detection of RNA polymerase II transcription start sites (TSSs). Accurate detection of TSSs enhances identification and discovery of core promoters. In addition, active enhancers can be detected through signatures of bidirectional transcription initiation. Described here is a protocol for performing super-low input carrier-CAGE (SLIC-CAGE). This SLIC adaptation of the CAGE protocol minimizes RNA losses by artificially increasing the RNA amount through use of an in vitro transcribed RNA carrier mix that is added to the sample of interest, thus enabling library preparation from nanogram-amounts of total RNA (i.e., thousands of cells). The carrier mimics the expected DNA library fragment length distribution, thereby eliminating biases that could be caused by the abundance of a homogenous carrier. In the last stages of the protocol, the carrier is removed through degradation with homing endonucleases and the target library is amplified. The target sample library is protected from degradation, as the homing endonuclease recognition sites are long (between 18 and 27 bp), making the probability of their existence in the eukaryotic genomes very low. The end result is a DNA library ready for next-generation sequencing. All steps in the protocol, up to sequencing, can be completed within 6 days. The carrier preparation requires a full working day; however, it can be prepared in large quantities and kept frozen at -80 °C. Once sequenced, the reads can be processed to obtain genome-wide single-nucleotide resolution TSSs. TSSs can be used for core promoter or enhancer discovery, providing insight into gene regulation. Once aggregated to promoters, the data can also be used for 5'-centric expression profiling.[SEP]Relations: HIV Transcription Initiation has relations: pathway_protein with TAF4, pathway_protein with TAF4, pathway_protein with TAF2, pathway_protein with TAF2, pathway_protein with TAF6, pathway_protein with TAF6, pathway_protein with TAF3, pathway_protein with TAF3, pathway_protein with TAF5, pathway_protein with TAF5. Definitions: RNA defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). Transcription Start Site defined as following: The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. promoter defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. CAGE defined as following: A method for high-throughout gene expression analysis and the profiling of transcriptional start points (TSP), including promoter usage analysis. It uses cap-selected full length cDNAs with linkers attached to their 5' ends which are then cleaved to about 20 base pairs, amplified by PCR, contatamerized, and cloned.. RNA polymerase II defined as following: A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC 2.7.7.6.. germ cells defined as following: The reproductive cells in multicellular organisms at various stages during GAMETOGENESIS..", "label": "no"} {"id": "converted_3040", "sentence1": "Is baricitinib effective for rheumatoid arthritis?", "sentence2": "CONCLUSION: Baricitinib 2 mg and 4 mg administered once daily, in combination with DMARD, were efficacious interventions for active RA that had no significant risk of TEAE development., CONCLUSIONS: The efficacy and safety profile of baricitinib was maintained during long-term treatment of Japanese patients with RA and background methotrexate therapy., CONCLUSION: In a phase IIb study in RA, the safety and tolerability profile of baricitinib, up to 128 weeks, remained consistent with earlier observations, without unexpected late signals. Clinical improvements seen in the 24-week blinded period were maintained during the OLE., CONCLUSION: Data for baricitinib, with/without methotrexate, in Japanese subpopulations across all stages of the RA treatment continuum accord with the efficacy/safety profile in overall study populations., Conclusion: Baricitinib demonstrated a consistent, beneficial treatment effect in bDMARD-refractory patients across subgroups based on baseline characteristics and prior bDMARD use., Baricitinib is effective in treatment of RA, and did not appear to have significant safety concerns during the first 6 months of treatment., OBJECTIVE\nBaricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA)., EXPERT OPINION\nJAK inhibitors are effective in the treatment of rheumatoid arthritis as evidenced by several inhibitors enabling the majority of treated patients to achieve ACR20 responses, with baricitinib and INCB-039110 both effective when administered once daily., OBJECTIVE\nBaricitinib is an oral, once-daily selective Janus kinase (JAK1/JAK2) inhibitor for adults with moderately to severely active rheumatoid arthritis (RA)., Two different Janus kinase (JAK) inhibitors-baricitinib and tofacitinib-are effective and licensed in active rheumatoid arthritis (RA)., Baricitinib for the treatment of rheumatoid arthritis., OBJECTIVES\nOral targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), including the Janus kinase inhibitors tofacitinib and baricitinib, are the latest addition to the therapeutic options for rheumatoid arthritis (RA)., Baricitinib (Olumiant™) is an orally-administered, small-molecule, janus-associated kinase (JAK) inhibitor developed by Eli Lilly and Incyte Corporation for the treatment of rheumatoid arthritis (RA), atopic dermatitis and systemic lupus erythematosus., EXPERT OPINION JAK inhibitors are effective in the treatment of rheumatoid arthritis as evidenced by several inhibitors enabling the majority of treated patients to achieve ACR20 responses, with baricitinib and INCB-039110 both effective when administered once daily., Tofacitinib 10 mg + methotrexate (MTX) and baricitinib 4 mg + MTX were among the most effective treatments for active RA with an inadequate DMARD or biologic response, followed by baricitinib 2 mg + MTX, tofacitinib 5 mg + MTX, and adalimumab + MTX., OBJECTIVE Baricitinib is an orally administered inhibitor of JAK1 and JAK2 that has been shown to be effective in treating rheumatoid arthritis (RA)., CONCLUSIONS In patients with rheumatoid arthritis who had had an inadequate response to methotrexate, baricitinib was associated with significant clinical improvements as compared with placebo and adalimumab., Thus, once-daily baricitinib, as monotherapy or in combination with methotrexate, is an effective and generally well tolerated emerging treatment for patients with moderate to severe active RA who have responded inadequately to or are intolerant of ≥ 1 DMARD, and extends the options available for this population., OBJECTIVES Oral targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs), including the Janus kinase inhibitors tofacitinib and baricitinib, are the latest addition to the therapeutic options for rheumatoid arthritis (RA)., Five phase 3 trials of Baricitinib, a JAK1 and JAK2 inhibitor, have been performed and showed high clinical efficacy in patients with active RA and naïve to sDMARDs or an inadequate response to sDMARDs, MTX or bDMARDs., It is also reported that safety was tolerable within the limited study period.Tetanus, diphtheria, and pertussis (whooping cough) are serious bacterial infections. Tetanus causes painful tightening of the muscles, usually all over the body. It can lead to \"locking\" of the jaw. Diphtheria usually affects the nose and throat. Whooping cough causes uncontrollable coughing. Vaccines can protect you from these diseases. In the U.S., there are four combination vaccines:
Some people should not get these vaccines, including those who have had severe reactions to the shots before. Check with your doctor first if you have seizures, a neurologic problem, or Guillain-Barre syndrome. Also let your doctor know if you don't feel well the day of the shot; you may need to postpone it.
Centers for Disease Control and Prevention
. diarrhea defined as following: An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.. intestinal inflammation defined as following: A reaction characterizeds by capillary dilatation, leukocytic infiltration, redness, heat, pain, swelling localized to the in the intestinal tract. [PMID:9897960]. rectosigmoid colon defined as following: A portion of the large intestine that includes the descending colon, sigmoid colon and rectum.. anxiety defined as following: Persistent and disabling ANXIETY.. Autistic behavior defined as following: Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior. [HPO:probinson, PMID:28879490]. ASD defined as following: Developmental abnormalities in any portion of the ATRIAL SEPTUM resulting in abnormal communications between the two upper chambers of the heart. Classification of atrial septal defects is based on location of the communication and types of incomplete fusion of atrial septa with the ENDOCARDIAL CUSHIONS in the fetal heart. They include ostium primum, ostium secundum, sinus venosus, and coronary sinus defects.. bloody stools defined as following: A finding indicating the presence of blood in stool. It is the result of gastrointestinal hemorrhage and it may be easily seen in stool or may be identified microscopically..", "label": "yes"} {"id": "converted_4138", "sentence1": "Is methotrexate used for the treatment of Rheumatoid Arthritis (RA)?", "sentence2": "The use of methotrexate in rheumatoid arthritis., Historical perspective on the use of methotrexate for the treatment of rheumatoid arthritis., Aminopterin, a folic acid analogue was first reported in 1948 to produce temporary remission of acute leukemia of children, was also reported in 1951 to produce an important and rapid improvement in patients with rheumatoid arthritis (RA) and psoriasis, The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis., Methotrexate (MTX) is currently under study for use in juvenile rheumatoid arthritis. , The rational use of methotrexate in rheumatoid arthritis and other rheumatic diseases., Methotrexate-induced hepatic cirrhosis is less common in rheumatoid arthritis than previously thought, although its occurrence in psoriasis is probably higher than in rheumatoid arthritis. , Methotrexate is clearly effective in the treatment of rheumatoid arthritis and may be able to decrease the rate of formation of new bony erosions. , The use of methotrexate in rheumatoid arthritis., Review of the international literature on the clinical use of MTX in rheumatoid arthritis (RA) disease., MTX has emerged as a relatively safe and effective treatment for RA that compares favorably with other therapies, particularly because of its considerably longer median drug survival., The objective of this review is to update the recommendations of the 2010 Italian Consensus on the use of methotrexate (MTX) in rheumatoid arthritis (RA) and other rheumatic diseases, A new recommendation for patients with RA who are in MTX-induced clinical remission was also proposed and approved by the panel. Updated recommendations for the use of MTX in patients with RA or other rheumatologic disease are proposed., Methotrexate has been used in treatment of rheumatoid arthritis (RA) since the 1980s and to this day is often the first line medication for RA treatment., OBJECTIVE: Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries., Low dose pulse methotrexate (MTX) has become a widely used therapy for rheumatoid arthritis (RA) because of its good response rate profile. With, Treatment with methotrexate (MTX) in rheumatoid arthritis (RA) can lead to severe side-effects, especially pulmonary and haematological complications. The ai, Patients having rheumatoid arthritis (RA) treated with methotrexate (MTX) are at an increased risk of developing lymphoproliferative disorder (LPD). Epstei, Increasingly, methotrexate (MTX) and sulphasalazine (SASP) are used initially for second-line therapy of rheumatoid arthritis (RA). Althoug, OBJECTIVES: The folate antagonist methotrexate (MTX) has become established as the most commonly used disease-modifying anti-rheumatic drug (DMARD) in the treatment of rheumatoid arthritis (RA) but is commonly discontinued due to adverse effe, e suspected methotrexate (MTX)-associated lymphoproliferative disorder (LPD) induced by MTX treatment for rheumatoid arthritis (RA). About , BACKGROUND: Treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA) leads to decreased total immunoglobulin (Ig) levels and impairs vaccine-specific IgG antibody levels following pneumococcal vaccinat, In rheumatoid arthritis (RA) treatment, the concomitant use of methotrexate has been shown to reduce the incidence of antibodies to infliximab (ATI), on the other hand, it is unclear whether azathioprine can reduce ATI production. We enro, Methotrexate (MTX) is known as a first-line synthetic disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA)., Biological treatments are expensive and using SC methotrexate can improve disease control in RA patients, thus potentially avoiding or delaying the requirement for future biological treatment., Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries., We reviewed existing recommendations on the use of MTX for the treatment of RA and summarized areas of agreement that could be relevant for least developed countries (LDCs).M, st covered some but not all of the following areas: baseline \"pre-MTX\" assessment (7/12;58%), prescription of MTX (10/12;83.3%), management of MTX side effects (6/12;50%), and special considerations (e.g., peri-operative management) (8/12; 66.7%). R, lectronic databases and registries were searched for recommendations on MTX use in RA, duplicates were eliminated, and the most updated version adopted when there were several versions on the same recommendation. , MTX must at the present time be used only in severe RA, refractory to more than one classical slow acting drug., MTX is as effective in treating RA as the other second line drugs and always more rapidly effective, perhaps because of anti-inflammatory properties., For the low doses used in RA (less than 15 mg/week), MTX is completely and rapidly absorbed with an active process membrane transport., Methotrexate, which is used for RA treatment, causes thrombocytopenia., Methorexate therapy in a patient with rheumatoid arthritis complicated by idiopathic thrombocytopenic purpura., This case shows that methotrexate may be used in patients diagnosed with RA that is associated with ITP under strict monitoring., Here, we report an RA case that also had ITP, which did not decrease in platelet count after methotrexate therapy., We started methotrexate therapy 10 mg per week for treatment of RA, and hydroxychloroquine therapy was stopped due to nonresponse., Methotrexate (MTX) is the anchor treatment for rheumatoid arthritis (RA) and has been very thoroughly studied in many different patient populations, as monotherapy and in combination with various other disease modifying antirheumatic drugs and biologic agents, as they became available., Although rheumatologists have been using methotrexate in the treatment of RA for some time, controlled studies have been needed to establish the safety and efficacy of this agent., Methotrexate is generally the first-line drug for the treatment of RA, psoriatic arthritis and other forms of inflammatory arthritis, and it enhances the effect of most biologic agents in RA., Despite the introduction of numerous biologic agents for the treatment of rheumatoid arthritis (RA) and other forms of inflammatory arthritis, low-dose methotrexate therapy remains the gold standard in RA therapy., A number of studies show the efficacy of methotrexate (MTX) for rheumatoid arthritis (RA) in general., Methotrexate (MTX) is currently the most frequently used drugs in the treatment of rheumatoid arthritis (RA)., Methotrexate (MTX) has been the anchor treatment in rheumatoid arthritis (RA) over the last 15 years, and is used in combination with biologic agents to enhance efficacy over the last decade or so.[SEP]Relations: Methotrexate has relations: drug_drug with Raltitrexed, drug_drug with Raltitrexed, drug_drug with Methohexital, drug_drug with Methohexital, drug_drug with Raltegravir, drug_drug with Raltegravir, drug_drug with Methadone, drug_drug with Methadone, drug_drug with Benzoic acid, drug_drug with Benzoic acid. Definitions: biologic agents defined as following: Endogenously synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.. methotrexate defined as following: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.. psoriasis defined as following: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.. folic acid defined as following: A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.. SASP defined as following: Thioredoxin (105 aa, ~12 kDa) is encoded by the human TXN gene. This protein plays a role in redox reactions, signaling and immunity.. acute leukemia defined as following: A clonal (malignant) hematopoietic disorder with an acute onset, affecting the bone marrow and the peripheral blood. The malignant cells show minimal differentiation and are called blasts, either myeloid blasts (myeloblasts) or lymphoid blasts (lymphoblasts).. rheumatoid arthritis defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. Aminopterin defined as following: A folic acid derivative used as a rodenticide that has been shown to be teratogenic.. azathioprine defined as following: An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed). sulphasalazine defined as following: A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid (see MESALAMINE) released in the colon. (From Martindale, The Extra Pharmacopoeia, 30th ed, p907). infliximab defined as following: A chimeric monoclonal antibody to TNF-ALPHA that is used in the treatment of RHEUMATOID ARTHRITIS; ANKYLOSING SPONDYLITIS; PSORIATIC ARTHRITIS and CROHN'S DISEASE.. LPD defined as following: A rare, benign process that affects the peritoneal cavity and is characterized by the formation of multiple small nodules that are composed of well differentiated smooth muscle. It usually affects adults in their late reproductive years. Most patients are asymptomatic. The tumor nodules may regress spontaneously.. ITP defined as following: Thrombocytopenia occurring in the absence of toxic exposure or a disease associated with decreased platelets. It is mediated by immune mechanisms, in most cases IMMUNOGLOBULIN G autoantibodies which attach to platelets and subsequently undergo destruction by macrophages. The disease is seen in acute (affecting children) and chronic (adult) forms.. low-dose defined as following: A reduced quantity of a therapeutic agent prescribed to be taken at one time or at stated intervals.. anti-inflammatory defined as following: Substances that reduce or suppress INFLAMMATION.. folate antagonist defined as following: Inhibitors of the enzyme, dihydrofolate reductase (TETRAHYDROFOLATE DEHYDROGENASE), which converts dihydrofolate (FH2) to tetrahydrofolate (FH4). They are frequently used in cancer chemotherapy. (From AMA, Drug Evaluations Annual, 1994, p2033). disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. rheumatic diseases defined as following: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement.. thrombocytopenia defined as following: An autosomal dominant disorder caused by mutation(s) in the ANKRD26 gene, encoding ANKRD26 protein. Additionally, in one family, a mutation(s) has been identified in the MASTL gene, encoding serine/threonine-protein kinase greatwall. The condition is characterized by mild to moderate bruisability.. RA defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated..", "label": "yes"} {"id": "converted_2959", "sentence1": "Is Adar3 involved in learning and memory?", "sentence2": "Adar3 Is Involved in Learning and Memory in Mice., The newest member of the A-I editing family of ADAR proteins, the vertebrate-specific ADAR3, is highly expressed in the brain, but its functional significance is unknown. In vitro studies have suggested that ADAR3 acts as a negative regulator of A-I RNA editing but the scope and underlying mechanisms are also unknown. Meta-analysis of published data indicates that mouse Adar3 expression is highest in the hippocampus, thalamus, amygdala, and olfactory region. Consistent with this, we show that mice lacking exon 3 of Adar3 (which encodes two double stranded RNA binding domains) have increased levels of anxiety and deficits in hippocampus-dependent short- and long-term memory formation. RNA sequencing revealed a dysregulation of genes involved in synaptic function in the hippocampi of Adar3-deficient mice. We also show that ADAR3 transiently translocates from the cytoplasm to the nucleus upon KCl-mediated activation in SH-SY5Y cells. These results indicate that ADAR3 contributes to cognitive processes in mammals., Adar3 Is Involved in Learning and Memory in Mice.-deficient mice. [SEP]Relations: ADARB2 has relations: anatomy_protein_present with brain, anatomy_protein_present with brain, anatomy_protein_present with midbrain, anatomy_protein_present with midbrain, anatomy_protein_present with blood, anatomy_protein_present with blood, anatomy_protein_present with cerebellar cortex, anatomy_protein_present with cerebellar cortex, anatomy_protein_present with liver, anatomy_protein_present with liver. Definitions: amygdala defined as following: Almond-shaped group of basal nuclei anterior to the INFERIOR HORN OF THE LATERAL VENTRICLE of the TEMPORAL LOBE. The amygdala is part of the limbic system.. nucleus defined as following: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). mammals defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. cytoplasm defined as following: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990). double stranded RNA binding domains defined as following: An RNA-binding motif characterized by an alpha-beta-beta-beta-alpha fold that binds DOUBLE-STRANDED RNA. It occurs in many eukaryotic proteins as well as in bacterial and viral proteins.. anxiety defined as following: Persistent and disabling ANXIETY..", "label": "yes"} {"id": "converted_1689", "sentence1": "Is Achondroplasia associated with hearing loss?", "sentence2": "A hearing screening program was performed to determine the prevalence of hearing loss and abnormal tympanometry in individuals with short-stature skeletal dysplasias attending a national meeting. Behavioral audiometry, otoacoustic emission testing, and tympanometry were used to assess hearing. Failed hearing screen was defined as hearing ≥ 35 dB at one or more frequencies or by \"fail\" on otoacoustic emissions. One hundred ten of 112 subjects completed the screening. 58 (51.8%) were children. Seventy-three (65.2%) had achondroplasia, 34 (30.4%) had one of 11 other diagnoses, and 5(4.4%) were undiagnosed. 25.8% of children failed hearing screening in one or both ears, while 46.3% of adults failed in one or both ears. 55.1% of adults and 25.0% of children with achondroplasia failed screening., Forty-four children had achondroplasia, and 31 had normal hearing in both ears (71%); 8 failed hearing screening in 1 ear (18%), and 3 in both ears (7%). Tympanometry was performed in 45 children, with normal tympanograms found in 21 (47%), bilateral abnormal tympanograms in 15 (33%), and unilateral abnormal tympanograms in 9 (20%). Fourteen children with achondroplasia had normal tympanograms (42%); 11 had bilateral abnormal tympanograms (33%); and 8 had unilateral abnormal tympanograms (24%). For those children without functioning tympanostomy tubes, there was a 9.5 times greater odds of hearing loss if there was abnormal tympanometry (P = .03)., Achondroplasia (MIM 100800) is the most common non-lethal skeletal dysplasia. Its incidence is between one in 10,000 and one in 30,000. The phenotype is characterized by rhizomelic disproportionate short stature, enlarged head, midface hypoplasia, short hands and lordotic lumbar spine, associated with normal cognitive development. This autosomal-dominant disorder is caused by a gain-of-function mutation in the gene encoding the type 3 receptor for fibroblast growth factor (FGFR3); in more than 95% of cases, the mutation is G380R. The diagnosis is suspected on physical examination and confirmed by different age-related radiological features. Anticipatory and management care by a multidisciplinary team will prevent and treat complications, including cervical cord compression, conductive hearing loss and thoracolumbar gibbosity., The report includes information on otitis media, ventilation tubes, hearing loss, tonsillectomy, speech problems, tibial bowing and osteotomy, ventricular shunting, apnoea, cervicomedullary decompression, and neurological signs attributable to spinal stenosis., We conclude that verbal comprehension is significantly impaired in children with achondroplasia. This partial deficiency is probably related to frequent middle ear infections and resulting conductive hearing loss., In order to determine whether these morphologic changes are the cause of the hearing deficit in achondroplasia, audiometric studies and ENT evaluation were performed in eight of the nine patients., Audiograms were obtained in six of the nine achondroplastic subjects (two adults and four children). There was evidence of mixed hearing loss in the four children, but only of sensorineural hearing loss in the adults. We believe that the persistent hearing loss in achondroplasia is not due to sequelae of otitis media as some authors have suggested. , The AA report a clinical and radiological study performed in 18 achondroplastic patients in order to achieve a nosological settlement of the otological impairments. [SEP]Relations: achondroplasia has relations: disease_phenotype_positive with Hearing impairment, disease_phenotype_positive with Hearing impairment, disease_phenotype_positive with Conductive hearing impairment, disease_phenotype_positive with Conductive hearing impairment, disease_phenotype_positive with Functional abnormality of the middle ear, disease_phenotype_positive with Functional abnormality of the middle ear. Hearing impairment has relations: disease_phenotype_positive with achondroplasia, disease_phenotype_positive with achondroplasia, disease_phenotype_positive with severe achondroplasia-developmental delay-acanthosis nigricans syndrome, disease_phenotype_positive with severe achondroplasia-developmental delay-acanthosis nigricans syndrome. Definitions: gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. FGFR3 defined as following: Fibroblast growth factor receptor 3 (806 aa, ~88 kDa) is encoded by the human FGFR3 gene. This protein is involved in fibroblast growth factor signaling and skeletal development.. hearing loss defined as following: A condition in which a person partially loses the ability to hear sounds in one or both ears.. achondroplasia defined as following: An autosomal dominant disorder that is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and mid-face hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, GENU VARUM, and trident hand. (Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/Omim, MIM#100800, April 20, 2001). sensorineural hearing loss defined as following: Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.. AA defined as following: A rare autosomal dominant inherited chorioretinal degenerative disease presenting at birth or during infancy. The disease has characteristics of progressive bilateral retinal and choroidal atrophy which appears as lesions on the optic nerve and peripheral ocular fundus and leads to loss of central vision. Congenital anterior polar cataracts are sometimes associated with this disease. There is evidence this disease is caused by heterozygous mutation in the TEA domain family member-1 gene (TEAD1) on chromosome 11p15.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. fibroblast growth factor defined as following: A recombinant therapeutic agent which is chemically identical to or similar to endogenous fibroblast growth factor 1 (FGF-1. Because of the mitogenic and angiogenetic effects of FGF-1 on fibroblasts and endothelial cells, therapeutic FGF-1 has a potential role in wound healing; because FGF-1 has been shown to induce neurogenesis, therapeutic FGF-1 may have a role in nerve regeneration. (NCI04). tibial defined as following: The second longest bone of the skeleton. It is located on the medial side of the lower leg, articulating with the FIBULA laterally, the TALUS distally, and the FEMUR proximally.. apnoea defined as following: A transient absence of spontaneous respiration.. Achondroplasia defined as following: An autosomal dominant disorder that is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and mid-face hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, GENU VARUM, and trident hand. (Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/Omim, MIM#100800, April 20, 2001).", "label": "yes"} {"id": "converted_381", "sentence1": "Is cadasil syndrome a hereditary disease?", "sentence2": " CADASIL is the most frequent hereditary small-vessel disease of the brain. The clinical impact of various MR imaging markers has been repeatedly studied in this disorder, but alterations of contrast between gray matter and normal-appearing white matter remain unknown. The aim of this study was to evaluate the contrast alterations between gray matter and normal-appearing white matter on T1-weighted images in patients with CADASIL compared with healthy subjects, (CADASIL) is the most common form of hereditary cerebral angiopathy, Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease, clinically characterized by migraine, recurrent transient ischemic attacks or strokes, psychiatric disorders and cognitive decline. Strokes are typically ischemic, while hemorrhagic events have been only sporadically described, Mutations in the TREX1 and NOTCH3 genes cause retinal vasculopathy with cerebral leukodystrophy (RVCL) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), respectively, We used immunohistochemistry and immunogold electron microscopy (EM) to examine the distribution of GOM and NOTCH3 ectodomain (N3ECD) protein in microvasculature of brain gray matter and white matter in patients with CADASIL, non-CADASIL hereditary small-vessel disease and sporadic age-related degenerative disease, and comparable-age controls[SEP]Relations: CARASIL syndrome has relations: disease_phenotype_positive with Autosomal recessive inheritance, disease_phenotype_positive with Autosomal recessive inheritance, disease_disease with cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy,, disease_disease with cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy,, disease_protein with HTRA1, disease_protein with HTRA1. genetic cerebral small vessel disease has relations: disease_disease with genetic central nervous system and retinal vascular disease, disease_disease with genetic central nervous system and retinal vascular disease, disease_disease with Coats plus syndrome, disease_disease with Coats plus syndrome. Definitions: RVCL defined as following: An inherited group of small vessel diseases comprised of cerebroretinal vasculopathy (CRV), hereditary vascular retinopathy (HRV) and hereditary endotheliopathy with retinopathy, nephropathy and stroke all exhibiting progressive visual impairment as well as variable cerebral dysfunction. There is evidence the disease is caused by heterozygous mutation in the TREX1 gene on chromosome 3p21.. psychiatric disorders defined as following: Troublesome or disruptive behavioral displays.. CADASIL defined as following: A hereditary cerebrovascular disorder caused by mutations in the Notch 3 gene. It is characterized by alterations of the muscular wall of the small vessels in the brain, resulting in transient ischemic attacks. It may lead to cognitive problems and dementia.. Strokes defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810). TREX1 defined as following: Three prime repair exonuclease 1 (369 aa, ~39 kDa) is encoded by the human TREX1 gene. This protein is involved in DNA mismatch repair.. migraine defined as following: A common, severe type of vascular headache often associated with increased sympathetic activity, resulting in nausea, vomiting, and light sensitivity.. cerebral small vessel disease defined as following: Pathological processes or diseases where cerebral MICROVESSELS show abnormalities. They are often associated with aging, hypertension and risk factors for lacunar infarcts (see LACUNAR INFARCTION); LEUKOARAIOSIS; and CEREBRAL HEMORRHAGE.. cognitive decline defined as following: Loss of previously present mental abilities, generally in adults. [HPO:probinson]. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. leukoencephalopathy defined as following: Any of various diseases affecting the white matter of the central nervous system.. cadasil syndrome defined as following: A hereditary cerebrovascular disorder caused by mutations in the Notch 3 gene. It is characterized by alterations of the muscular wall of the small vessels in the brain, resulting in transient ischemic attacks. It may lead to cognitive problems and dementia.. hereditary disease defined as following: Genetic diseases are diseases in which inherited genes predispose to increased risk. The genetic disorders associated with cancer often result from an alteration or mutation in a single gene. The diseases range from rare dominant cancer family syndrome to familial tendencies in which low-penetrance genes may interact with other genes or environmental factors to induce cancer. Research may involve clinical, epidemiologic, and laboratory studies of persons, families, and populations at high risk of these disorders..", "label": "yes"} {"id": "converted_4162", "sentence1": "Are somatic mutations positioned towards the nuclear periphery?", "sentence2": "lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core., Furthermore, mutational signatures differed between the nuclear core and periphery, thus indicating differences in the patterns of DNA-damage or DNA-repair processes. For instance, smoking and UV-related signatures, as well as substitutions at certain motifs, were more enriched in the nuclear periphery. , We found that lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core., found that lamina-associated regions, which are typically localized at the nuclear periphery, displayed higher somatic mutation frequencies than did the interlamina regions at the nuclear core. Thi[SEP]Relations: regulation of protein localization to cell division site involved in mitotic actomyosin contractile ring assembly has relations: bioprocess_bioprocess with negative regulation of protein localization to cell division site involved in mitotic actomyosin contractile ring assembly, bioprocess_bioprocess with negative regulation of protein localization to cell division site involved in mitotic actomyosin contractile ring assembly, bioprocess_bioprocess with regulation of protein localization to cell division site, bioprocess_bioprocess with regulation of protein localization to cell division site, bioprocess_bioprocess with positive regulation of protein localization to cell division site involved in mitotic actomyosin contractile ring assembly, bioprocess_bioprocess with positive regulation of protein localization to cell division site involved in mitotic actomyosin contractile ring assembly, bioprocess_bioprocess with regulation of cell cycle process, bioprocess_bioprocess with regulation of cell cycle process.", "label": "yes"} {"id": "converted_3540", "sentence1": "Is TIM-3 a target for cancer immunotherapy in NSCLC?", "sentence2": " Our results imply that implementing combined treatment on CIK cells before transfusion via antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients., Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation. , In present study, we detected the dynamic expression of eight major checkpoint molecules (CTLA-4, PD-1, PD-L1, TIM- 3, CEACAM-1, LAG-3, TIGIT and BTLA) on CIK cells from NSCLC patients., Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors on T cells and other approaches such as adoptive cell transfer are tested for clinical efficacy in melanoma as well., We found immune activation coexistent with elevation of multiple targetable immune checkpoint molecules, including PD-L1, PD-L2, PD-1, TIM-3, B7-H3, BTLA, and CTLA-4, along with increases in tumor infiltration by CD4(+)Foxp3(+) regulatory T cells in lung adenocarcinomas that displayed an EMT phenotype, Cytometric profiling identified an immunologically \"hot\" cluster with abundant CD8+ T cells expressing high levels of PD-1 and TIM-3 and an immunologically \"cold\" cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers, Interestingly, CD161+ CD4+ T cells highly express OX40 co-stimulatory receptor, less frequently 4-1BB, and display an activated but not completely exhausted PD-1-positive Tim-3-negative phenotype., . Furthermore, overexpression of targetable immune checkpoints, such as CTLA-4 and TIM-3 were associated with EMT in both NSCLCs. [SEP]Relations: small cell lung carcinoma has relations: disease_protein with ASCL1, disease_protein with ASCL1, disease_protein with TP73, disease_protein with TP73, disease_protein with EPHB3, disease_protein with EPHB3. Protein S human has relations: drug_drug with NS-398, drug_drug with NS-398, drug_drug with Antithrombin III human, drug_drug with Antithrombin III human. Definitions: PD-1 defined as following: Human PDCD1 wild-type allele is located in the vicinity of 2q37.3 and is approximately 9 kb in length. This allele, which encodes programmed cell death protein 1, plays a role in the modulation of both apoptosis and cellular immunity. Mutation of the gene is associated with systemic lupus erythematosus type 2.. Tim-3 defined as following: Human HAVCR2 wild-type allele is located in the vicinity of 5q33.3 and is approximately 57 kb in length. This allele, which encodes hepatitis A virus cellular receptor 2 protein, is involved in the activation of macrophages and helper T cells.. CTLA-4 defined as following: An inhibitory T CELL receptor that is closely related to CD28 ANTIGEN. It has specificity for CD80 ANTIGEN and CD86 ANTIGEN and acts as a negative regulator of peripheral T cell function. CTLA-4 antigen is believed to play role in inducing PERIPHERAL TOLERANCE.. T cells defined as following: A subset of therapeutic autologous T-lymphocytes that express a T-cell receptor (TCR) composed of one gamma chain and one delta chain, with potential immunomodulating and antineoplastic activities. Upon administration of the therapeutic gamma delta T-lymphocytes, these cells secrete interferon-gamma (IFN-g), and exert direct killing of tumor cells. In addition, these cells activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response against tumor cells. Gamma delta T-lymphocytes play a key role in the activation of the immune system and do not require major histocompatibility complex (MHC)-mediated antigen presentation to exert their cytotoxic effect.. TIGIT defined as following: T-cell immunoreceptor with Ig and ITIM domains (244 aa, ~26 kDa) is encoded by the human TIGIT gene. This protein is involved in immunomodulation and cell-cell adhesion.. PD-L2 defined as following: Programmed cell death 1 ligand 2 (273 aa, ~31 kDa) is encoded by the human PDCD1LG2 gene. This protein is involved in the modulation of both T-cell proliferation and cytokine production.. CEACAM1 defined as following: Carcinoembryonic antigen-related cell adhesion molecule 1 (526 aa, ~58 kDa) is encoded by the human CEACAM1 gene. This protein is involved in differentiation, angiogenesis, apoptosis, immune response, and tumorigenesis.. CIK cells defined as following: A preparation of cytokine-induced killer (CIK) cells, with potential immunopotentiating and antineoplastic activities. CIK cells are generated from peripheral blood lymphocytes (PBLs) by sequential ex vivo incubation with a monoclonal antibody against CD3 (anti-CD3), interferon-gamma (IFN-g) and interleukin-2 (IL-2), followed by expansion. CIK cells are heterogeneous cells comprising CD3+CD56- T cells, CD3-CD56+ natural killer (NK) cells, and CD3+CD56+ natural killer T (NKT) cells. Upon administration of the CIK cells into the patient, the terminally differentiated CD3- and CD56-positive subset of the CIK cells primarily exert the direct MHC-unrestricted tumor killing activity.. BTLA defined as following: B- and T-lymphocyte attenuator (289 aa, ~33 kDa) is encoded by the human BTLA gene. This protein is involved in the regulation of immune responses.. LAG-3 defined as following: Lymphocyte activation gene 3 protein (525 aa, ~57 kDa) is encoded by the human LAG3 gene. This protein is involved in the activation of T-cells and natural killer cells.. PD-L1 defined as following: Human CD274 wild-type allele is located in the vicinity of 9p24 and is approximately 20 kb in length. This allele, which encodes programmed cell death 1 ligand 1 protein, plays a role in the regulation of T cell stimulation and proliferation.. melanoma defined as following: A benign or malignant, primary or metastatic neoplasm affecting the melanocytes.. NSCLC defined as following: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.. B7-H3 defined as following: CD276 antigen (534 aa, ~57 kDa) is encoded by the human CD276 gene. This protein is involved in the mediation of T cell proliferation and activation.. TIM-3 defined as following: Human HAVCR2 wild-type allele is located in the vicinity of 5q33.3 and is approximately 57 kb in length. This allele, which encodes hepatitis A virus cellular receptor 2 protein, is involved in the activation of macrophages and helper T cells..", "label": "yes"} {"id": "converted_2378", "sentence1": "Is a CpG island methylator phenotype involved in ependymomas?", "sentence2": "Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype, Although no recurrently mutated genes were found throughout these groups of ependymomas, PFA exhibited a CpG island methylator phenotype, PFB was associated with extensive chromosomal aberrations, and the C11orf95-RELA fusion gene was frequently observed in supratentorial ependymomas. , Supratentorial and spinal pediatric ependymomas display a hypermethylated phenotype which includes the loss of tumor suppressor genes involved in the control of cell growth and death., Supratentorial and spinal tumors displayed significantly more hypermethylated genes than posterior fossa tumors, similar to the 'CpG island methylator phenotype' (CIMP) identified in glioma and colon carcinoma., The data suggests epigenetic silencing of tumor suppressor genes is an important mechanism in the pathogenesis of supratentorial and spinal, but not posterior fossa ependymomas. Hypermethylation correlated with a decrease in expression of a number of tumor suppressor genes and pathways that could be playing an important role in tumor pathogenesis., Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype., CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo., Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants., Although no recurrently mutated genes were found throughout these groups of ependymomas, PFA exhibited a CpG island methylator phenotype, PFB was associated with extensive chromosomal aberrations, and the C11orf95-RELA fusion gene was frequently observed in supratentorial ependymomas., ependymomas are common childhood brain tumours that occur throughout the nervous system but are most common in the paediatric hindbrain current standard therapy comprises surgery and radiation but not cytotoxic chemotherapy as it does not further increase survival whole genome and whole exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate and zero significant recurrent somatic single nucleotide variants although devoid of recurrent single nucleotide variants and focal copy number aberrations poor prognosis hindbrain ependymomas exhibit a cpg island methylator phenotype transcriptional silencing driven by cpg methylation converges exclusively on targets of the polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of h3k27 cpg island methylator phenotype positive hindbrain ependymomas are responsive to clinical drugs that target either dna or h3k27 methylation both in vitro and in vivo we conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy which is epigenetically deregulated but genetically bland., supratentorial and spinal pediatric ependymomas display a hypermethylated phenotype which includes the loss of tumor suppressor genes involved in the control of cell growth and death, epigenomic alterations define lethal cimp positive ependymomas of infancy, molecular genetics of ependymomas and pediatric diffuse gliomas a short review, epigenetic alterations including methylation have been shown to be an important mechanism of gene silencing in cancer ependymoma has been well characterized at the dna copy number and mrna expression levels however little is known about dna methylation changes to gain a more global view of the methylation profile of ependymoma we conducted an array based analysis our data demonstrated tumors to segregate according to their location in the cns which was associated with a difference in the global level of methylation supratentorial and spinal tumors displayed significantly more hypermethylated genes than posterior fossa tumors similar to the cpg island methylator phenotype cimp identified in glioma and colon carcinoma this hypermethylated profile was associated with an increase in expression of genes encoding for proteins involved in methylating dna suggesting an underlying mechanism an integrated analysis of methylation and mrna expression array data allowed us to identify methylation induced expression changes most notably genes involved in the control of cell growth and death and the immune system were identified including members of the jnk pathway and pparg in conclusion we have generated a global view of the methylation profile of ependymoma the data suggests epigenetic silencing of tumor suppressor genes is an important mechanism in the pathogenesis of supratentorial and spinal but not posterior fossa ependymomas hypermethylation correlated with a decrease in expression of a number of tumor suppressor genes and pathways that could be playing an important role in tumor pathogenesis., here we review the recent literature on molecular discoveries in ependymomas and pediatric diffuse gliomas ependymomas can now be categorized into three location related subgroups according to their biological profile posterior fossa ependymomas group a pfa and b pfb and supratentorial ependymomas although no recurrently mutated genes were found throughout these groups of ependymomas pfa exhibited a cpg island methylator phenotype pfb was associated with extensive chromosomal aberrations and the c11orf95 rela fusion gene was frequently observed in supratentorial ependymomas meanwhile it has now become apparent that pediatric diffuse gliomas have a distinct genetic status from their adult counterparts even though they share an indistinguishable histology in pediatric low grade diffuse gliomas an intragenic duplication of the portion of fgfr1 encoding the tyrosine kinase domain tkd and rearrangements of myb mybl1 were found recurrently and mutually exclusively as for non brainstem high grade tumors in addition to h3f3a tp53 and atrx mutations which were frequently observed in older children recurrent fusions involving ntrk1 ntrk2 and ntrk3 were reported in infants younger than 3 years of age moreover in diffuse intrinsic pontine gliomas dipg recurrent somatic mutations of acvr1 were found in association with hist1h3b mutations.[SEP]Relations: ependymoma has relations: disease_phenotype_positive with Ependymoma, disease_phenotype_positive with Ependymoma, disease_phenotype_positive with Seizure, disease_phenotype_positive with Seizure, disease_phenotype_positive with Neoplasm of the lung, disease_phenotype_positive with Neoplasm of the lung, disease_phenotype_positive with Abnormal cell morphology, disease_phenotype_positive with Abnormal cell morphology. Glioma has relations: phenotype_phenotype with Ependymoma, phenotype_phenotype with Ependymoma. Definitions: ependymomas defined as following: Glioma derived from EPENDYMOGLIAL CELLS that tend to present as malignant intracranial tumors in children and as benign intraspinal neoplasms in adults. It may arise from any level of the ventricular system or central canal of the spinal cord. Intracranial ependymomas most frequently originate in the FOURTH VENTRICLE and histologically are densely cellular tumors which may contain ependymal tubules and perivascular pseudorosettes. Spinal ependymomas are usually benign papillary or myxopapillary tumors. (From DeVita et al., Principles and Practice of Oncology, 5th ed, p2018; Escourolle et al., Manual of Basic Neuropathology, 2nd ed, pp28-9). C11orf95-RELA fusion gene defined as following: A fusion gene that results from chromothripsis involving chromosome 11q13.1, which fuses the first 2, 3 or 4 exons of the ZFTA gene to sequences that are located 5' of either exon 2 or 3 of the RELA gene. This rearrangement is associated with supratentorial ependymoma.. spinal tumors defined as following: Benign and malignant neoplasms which occur within the substance of the spinal cord (intramedullary neoplasms) or in the space between the dura and spinal cord (intradural extramedullary neoplasms). The majority of intramedullary spinal tumors are primary CNS neoplasms including ASTROCYTOMA; EPENDYMOMA; and LIPOMA. Intramedullary neoplasms are often associated with SYRINGOMYELIA. The most frequent histologic types of intradural-extramedullary tumors are MENINGIOMA and NEUROFIBROMA.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. colon carcinoma defined as following: A malignant epithelial neoplasm that arises from the colon and invades through the muscularis mucosa into the submucosa. The vast majority are adenocarcinomas.. glioma defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21). PFA defined as following: This gene is involved in desmosome formation.. cns defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. h3f3a defined as following: Human H3-3A wild-type allele is located in the vicinity of 1q42.12 and is approximately 10 kb in length. This allele, which encodes histone H3.3 protein, plays a role in both nucleosome assembly and transcriptional regulation.. acvr1 defined as following: Activin receptor type-1 (509 aa, ~57 kDa) is encoded by the human ACVR1 gene. This protein is involved in embryonic development, protein phosphorylation, and signal transduction.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. mrna defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. fgfr1 defined as following: Fibroblast growth factor receptor 1 (822 aa, ~92 kDa) is encoded by the human FGFR1 gene. This protein is involved in the regulation of embryonic development, cell proliferation, cell differentiation and cellular migration.. ntrk3 defined as following: NT-3 growth factor receptor (839 aa, ~94 kDa) is encoded by the human NTRK3 gene. This protein is involved in ligand binding, tyrosine phosphorylation and neurotrophin-3-mediated signaling.. spinal defined as following: Of or relating to the spine or spinal cord.. pparg defined as following: Peroxisome proliferator-activated receptor gamma (505 aa, ~58 kDa) is encoded by the human PPARG gene. This protein plays a role in transcriptional regulation, lipid metabolism, cell differentiation, glucose homeostasis and apoptosis.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. molecular genetics defined as following: The study of the flow and regulation of genetic information between DNA, RNA, and protein molecules.. supratentorial ependymomas defined as following: A circumscribed ependymoma that arises from the supratentorial region of the brain. The diagnosis of supratentorial ependymoma should be made either when genetic analysis did not reveal a fusion gene involving ZFTA or YAP1 genes (not elsewhere classified -NEC) or when the genetic analysis was unsuccessful or not reported (not otherwise specified-NOS).. tumor suppressor genes defined as following: Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.. H3K27 defined as following: The lysine residue found at amino acid position 28 in the histone H3 protein. Methylation of this residue may be a marker for transcriptionally repressed genes.. CpG island defined as following: Areas of increased density of the dinucleotide sequence cytosine--phosphate diester--guanine. They form stretches of DNA several hundred to several thousand base pairs long. In humans there are about 45,000 CpG islands, mostly found at the 5' ends of genes. They are unmethylated except for those on the inactive X chromosome and some associated with imprinted genes..", "label": "yes"} {"id": "converted_2866", "sentence1": "Does simvastatin improve outcomes of aneurysmal subarachnoid hemorrhage?", "sentence2": "Randomized controlled trials have shown that simvastatin and intravenous magnesium do not prevent DCI or improve functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH)., Conclusions Simvastatin showed no benefits in decreasing the incidence of vasospasm, DCI, or all-cause mortality after aneurysmal SAH. We conclude that patients with SAH should not be treated routinely with simvastatin during the acute stage., We found no statistically significant effects on vasospasm detected by transcranial cerebral Doppler (relative risk [RR], 0.91; 95% confidence interval [CI], 0.55-1.49), delayed cerebral ischemia (DCI) (RR, 0.85; 95% CI, 0.63-1.14), or all-cause mortality (RR, 1.02; 95% CI, 0.67-1.54)., BACKGROUND: Simvastatin might be beneficial to the patients with aneurysmal subarachnoid hemorrhage. However, the results remained controversial. , CONCLUSIONS: Compared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS≤2, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage., Current evidence does not support prophylactic use of clazosentan, magnesium, or simvastatin. , Recently, acute simvastatin treatment was not shown to be beneficial in neurological outcome using modified Rankin Scale., CONCLUSIONS: The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage., CONCLUSION: This study demonstrated that 80 mg simvastatin treatment was effective in preventing cerebral vasospasm after aneurysmal SAH, but did not improve the clinical outcome in Korean patients., High-Dose Simvastatin Is Effective in Preventing Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study in Korean Patients., CONCLUSIONS\nThe current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage., CONCLUSIONS\nHigh-dose simvastatin treatment should not be prescribed routinely for aneurysmal subarachnoid hemorrhage., Randomized controlled trials have shown that simvastatin and intravenous magnesium do not prevent DCI or improve functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH)., CONCLUSIONS\nCompared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS≤2, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage., CONCLUSIONS The current study does not support that acute simvastatin treatment improves cognitive outcome after aneurysmal subarachnoid hemorrhage., CONCLUSIONS High-dose simvastatin treatment should not be prescribed routinely for aneurysmal subarachnoid hemorrhage., CONCLUSIONS Compared to control intervention, simvastatin intervention was found to have no influence on delayed ischaemic deficit, delayed cerebral infarction, mRS≤2, vasospasm, ICU stay, hospital stay, and mortality in patients with acute aneurysmal subarachnoid hemorrhage., There were also no differences in DID, delayed cerebral infarction, favorable mRS outcome, and MMSE scores, and MMSE-assessed cognitive impairment between both groups.PrEP and PEP are medicines to prevent HIV. Each type is used in a different situation:
PrEP is for people without HIV who are at very high risk for getting it. This includes:
Gay/bisexual men who
Heterosexual men and women who
People who inject drugs and
If you have a partner who is HIV-positive and are considering getting pregnant, talk to your health care provider about PrEP. Taking it may help protect you and your baby from getting HIV infection while you try to get pregnant, during pregnancy, or while breastfeeding.
PrEP is very effective when you take it every day. It reduces the risk of getting HIV from sex by more than 90%. In people who inject drugs, it reduces the risk of HIV by more than 70%. PrEP is much less effective if you do not take it consistently.
PrEP does not protect against other STDs, so you should still use latex condoms every time you have sex. If your or your partner is allergic to latex, you can use polyurethane condoms.
You must have an HIV test every 3 months while taking PrEP, so you'll have regular follow-up visits with your health care provider. If you are having trouble taking PrEP every day or if you want to stop taking PrEP, talk to your health care provider.
Some people taking PrEP may have side effects, like nausea. The side effects are usually not serious and often get better over time. If you are taking PrEP, tell your health care provider if you have a side effect that bothers you or that does not go away.
If you are HIV-negative and you think you may have been recently exposed to HIV, contact your health care provider immediately or go to an emergency room right away.
You may be prescribed PEP if you are HIV negative or don't know your HIV status, and in the last 72 hours you
Your health care provider or emergency room doctor will help to decide whether PEP is right for you.
PEP may also be given to a health care worker after a possible exposure to HIV at work, for example, from a needlestick injury.
PEP must be started within 72 hours (3 days) after a possible exposure to HIV. The sooner you start it, the better; every hour counts.
You need to take the PEP medicines every day for 28 days. You will have to see your health care provider at certain times during and after taking the PEP, so you can have an HIV screening test and other testing.
Some people taking PEP may have side effects, like nausea. The side effects are usually not serious and often get better over time. If you are taking PEP, tell your health care provider if you have a side effect that bothers you or that does not go away.
PEP medicines may also interact with other medicines that a person is taking (called a drug interaction). So it's important to tell your health care provider about any other medicines that you take.
PEP is only for emergency situations. It is not the right choice for people who may be exposed to HIV frequently - for example, if you often have sex without a condom with a partner who is HIV-positive. In that case, you should talk to your health care provider about whether PrEP (pre-exposure prophylaxis) would be right for you.
. HIV infections defined as following: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS)..", "label": "no"} {"id": "converted_4024", "sentence1": "Is the apilimod inhibitor effective against SARS-CoV-2?", "sentence2": "To identify therapeutics that can be repurposed as SARS-CoV-2 antivirals, we profiled a library of known drugs encompassing approximately 12,000 clinical-stage or FDA-approved small molecules. Here, we report the identification of 30 known drugs that inhibit viral replication. Of these, six were characterized for cellular dose-activity relationships, and showed effective concentrations likely to be commensurate with therapeutic doses in patients. These include the PIKfyve kinase inhibitor Apilimod, cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825, and ONO 5334, and the CCR1 antagonist MLN-3897. Since many of these molecules have advanced into the clinic, the known pharmacological and human safety profiles of these compounds will accelerate their preclinical and clinical evaluation for COVID-19 treatment.[SEP]Relations: protein serine/threonine kinase inhibitor activity has relations: molfunc_protein with SPRY2, molfunc_protein with SPRY2, molfunc_protein with INKA2, molfunc_protein with INKA2, molfunc_protein with SPRED2, molfunc_protein with SPRED2, molfunc_protein with CIB1, molfunc_protein with CIB1, molfunc_protein with INKA1, molfunc_protein with INKA1. Definitions: human defined as following: Members of the species Homo sapiens.. molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. cysteine protease inhibitors defined as following: Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES..", "label": "yes"} {"id": "converted_2552", "sentence1": "Is the consumption of chocolate associated with an increase in cardiovascular disease?", "sentence2": "The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke., chocolate has been shown to decrease CVD risk due to its antioxidant and anti-inflammatory properties., A number of studies have shown that dietary polyphenols exert a protective effect against hypertension, dyslipidemias, inflammation, endothelial function and atherosclerosis, conditions associated with increased risk for cardiovascular disease., Chocolate consumption may have a beneficial effect on cardiovascular health,, Data currently available indicate that daily consumption of cocoa-rich chocolate (rich in polyphenols) may at least partially lower cardiovascular disease risk., CONCLUSIONS The blood pressure and cholesterol lowering effects of dark chocolate consumption are beneficial in the prevention of cardiovascular events in a population with metabolic syndrome., Daily dark chocolate consumption could be an effective cardiovascular preventive strategy in this population., BACKGROUND The consumption of chocolate and cocoa has established cardiovascular benefits., CONCLUSIONS Chocolate consumption is associated with lower risk of MI and ischaemic heart disease., Chocolate consumption was inversely associated with MI risk., Chocolate consumption is associated with lower risk of MI and ischaemic heart disease., The consumption of cocoa/ chocolate (i) increases plasma antioxidant capacity, (ii) diminishes platelet function and inflammation, and (iii) decreases diastolic and systolic arterial pressures., Chocolate consumption was inversely associated with MI risk., Chocolate consumption is inversely associated with prevalent coronary heart disease: the National Heart, Lung, and Blood Institute Family Heart Study., Daily chocolate consumption is inversely associated with insulin resistance and liver enzymes in the Observation of Cardiovascular Risk Factors in Luxembourg study., Collectively, the antioxidant effects of flavonoid-rich foods may reduce cardiovascular disease risk., The consumption of cocoa and dark chocolate is associated with a lower risk of CVD, and improvements in endothelial function may mediate this relationship, It has been shown that the consumption of cocoa has a positive influence on a number of cardiovascular surrogate parameters such as arterial vasodilatation and a moderate decrease in blood pressure in humans. , This study has shown that increasing the polyphenol content of the diet via consumption of F&V, berries and dark chocolate results in a significant improvement in an established marker of cardiovascular risk in hypertensive participants., Cocoa flavonoids exert cardiovascular benefits and neuroprotection. , Accumulating evidence suggests potential preventive effects of chocolate/cocoa on the risk of cardio vascular disease (CVD).[SEP]Relations: cardiovascular disease has relations: disease_disease with heart disease, disease_disease with heart disease, contraindication with Caffeine, contraindication with Caffeine, disease_disease with vascular disease, disease_disease with vascular disease, disease_disease with cardiovascular neoplasm, disease_disease with cardiovascular neoplasm. heart disease has relations: disease_disease with cardiovascular disease, disease_disease with cardiovascular disease. Definitions: atherosclerosis defined as following: Thickening and loss of elasticity of the walls of ARTERIES of all sizes. There are many forms classified by the types of lesions and arteries involved, such as ATHEROSCLEROSIS with fatty lesions in the ARTERIAL INTIMA of medium and large muscular arteries.. hypertension defined as following: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.. humans defined as following: Members of the species Homo sapiens.. antioxidant defined as following: Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. CVD defined as following: A spectrum of pathological conditions of impaired blood flow in the brain. They can involve vessels (ARTERIES or VEINS) in the CEREBRUM, the CEREBELLUM, and the BRAIN STEM. Major categories include INTRACRANIAL ARTERIOVENOUS MALFORMATIONS; BRAIN ISCHEMIA; CEREBRAL HEMORRHAGE; and others.. metabolic syndrome defined as following: A combination of medical conditions that when present, increase the risk of heart attack, stroke, and diabetes mellitus. It includes the following medical conditions: increased blood pressure, central obesity, dyslipidemia, impaired glucose tolerance, and insulin resistance.. cardiovascular defined as following: The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body.. dyslipidemias defined as following: A lipoprotein metabolism disorder characterized by decreased levels of high-density lipoproteins, or elevated levels of plasma cholesterol, low-density lipoproteins and/or triglycerides.. ischaemic heart disease defined as following: Thickening and loss of elasticity of the CORONARY ARTERIES, leading to progressive arterial insufficiency (CORONARY DISEASE).. polyphenol defined as following: A large class of organic compounds having more than one PHENOL group.. cholesterol defined as following: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.. stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810). Cardiovascular Risk Factors defined as following: Aspects of personal behavior or lifestyle, environmental exposure, inherited conditions and characteristics, which are determined to be associated with HEART DISEASES..", "label": "no"} {"id": "converted_3849", "sentence1": "Can ATAC-Seq be employed in single-cell mode?", "sentence2": "Single-cell ATAC-seq: strength in numbers., Assembly, and Single-Cell ATAC-Seq., Single cell RNA-seq and ATAC-seq analysis of cardiac progenitor cell transition states and lineage settlement., Here, we comprehensively characterize mouse cardiac progenitor cells (CPCs) marked by Nkx2-5 and Isl1 expression from E7.5 to E9.5 using single-cell RNA sequencing and transposase-accessible chromatin profiling (ATAC-seq)., Classifying cells with Scasat, a single-cell ATAC-seq analysis tool., When done at single-cell resolution, ATAC-seq provides an insight into the cell-to-cell variability that emerges from otherwise identical DNA sequences by identifying the variability in the genomic location of open chromatin sites in each of the cells., Single-cell ATAC-Seq in human pancreatic islets and deep learning upscaling of rare cells reveals cell-specific type 2 diabetes regulatory signatures., THODS: We present genome-wide single-cell chromatin accessibility profiles in >1,600 cells derived from a human pancreatic islet sample using single-cell combinatorial indexing ATAC-seq (sci-ATAC-seq). W, Contiguity-Preserving Transposition Sequencing (CPT-Seq) for Genome-Wide Haplotyping, Assembly, and Single-Cell ATAC-Seq., SCALE method for single-cell ATAC-seq analysis via latent feature extraction., Single-cell ATAC-seq (scATAC-seq) profiles the chromatin accessibility landscape at single cell level, thus revealing cell-to-cell variability in gene regulation., The recently developed low-input and single-cell regulome mapping technologies such as ATAC-seq and single-cell ATAC-seq (scATAC-seq) allow analyses of small-cell-number and single-cell samples, but their signals remain highly discrete or noisy., This paper presents Scasat (single-cell ATAC-seq analysis tool), a complete pipeline to process scATAC-seq data with simple steps., Here, we comprehensively characterize mouse cardiac progenitor cells (CPCs) marked by Nkx2-5 and Isl1 expression from E7.5 to E9.5 using single-cell RNA sequencing and transposase-accessible chromatin profiling (ATAC-seq)., Single-cell ATAC-seq (scATAC-seq) technology has also been developed to study cell type-specific chromatin accessibility in tissue samples containing a heterogeneous cellular population., Here we combined sequencing of the TCR-encoding genes with assay for transposase-accessible chromatin with sequencing (ATAC-seq) analysis at the single-cell level to provide information on the TCR specificity and epigenomic state of individual T cells., Substantial advances of this work include the optimization of a single-cell combinatorial indexing assay for transposase accessible chromatin (sci-ATAC-seq); a software suite,, The accessible chromatin landscape of the murine hippocampus at single-cell resolution., Here we present a comprehensive map of the accessible chromatin landscape of the mouse hippocampus at single-cell resolution., We expect this review will provide a guideline for successful data generation and analysis methods using appropriate software tools and databases for the study of chromatin accessibility at single-cell resolution., Single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) is the state-of-the-art technology for analyzing genome-wide regulatory landscapes in single cells., Single-cell ATAC-seq data are sparse and noisy, and analyzing such data is challenging., Here, we introduce a method for analyzing scATAC-seq data, called Single-Cell ATAC-seq analysis via Latent feature Extraction (SCALE)., Single-cell ATAC-seq signal extraction and enhancement with SCATE., Single-cell ATAC-seq detects open chromatin in individual cells., Currently data are sparse, but combining information from many single cells can identify determinants of cell-to-cell chromatin variation., Predictions based on single-cell RNA-seq (scRNA-seq) can more accurately reconstruct bulk chromatin accessibility than using scATAC-seq., Global prediction of chromatin accessibility using small-cell-number and single-cell RNA-seq., Single-cell ATAC-seq (scATAC-seq) maps from hundreds of single cells in aggregate closely resemble accessibility profiles from tens of millions of cells and provide insights into cell-to-cell variation., However, very few studies have been performed at the single cell level (scATAC-seq) due to technical challenges., Here, we present Perturb-ATAC, a method that combines multiplexed CRISPR interference or knockout with genome-wide chromatin accessibility profiling in single cells based on the simultaneous detection of CRISPR guide RNAs and open chromatin sites by assay of transposase-accessible chromatin with sequencing (ATAC-seq)., Additionally, the same workflow can be used to aid de novo assembly (Adey et al., Genome Res 24(12):2041-2049, 2014), detect structural variants, and perform single cell ATAC-seq analysis (Cusanovich et al., Science 348(6237):910-914, 2015)., ChromA can analyze single cell ATAC-seq data, correcting many biases generated by the sparse sampling inherent in single cell technologies., circuits. Existing chromatin profiling methods such as ATAC-seq and DNase-seq, applied to islets in bulk, produce aggregate profiles that mask important cellular and regulatory heterogeneity.METHODS: We present genome-wide single-cell chromatin accessibility profiles in >1,600 cells derived from a human pancreatic islet sample using single-cell combinatorial indexing ATAC, ATAC-seq has become a leading technology for probing the chromatin landscape of single and aggregated cells.[SEP]Relations: transcription-coupled nucleotide-excision repair has relations: bioprocess_protein with AQR, bioprocess_protein with AQR, bioprocess_protein with XRCC1, bioprocess_protein with XRCC1, bioprocess_protein with POLR2C, bioprocess_protein with POLR2C, bioprocess_protein with CDK7, bioprocess_protein with CDK7, bioprocess_protein with ERCC1, bioprocess_protein with ERCC1. Definitions: T cells defined as following: A subset of therapeutic autologous T-lymphocytes that express a T-cell receptor (TCR) composed of one gamma chain and one delta chain, with potential immunomodulating and antineoplastic activities. Upon administration of the therapeutic gamma delta T-lymphocytes, these cells secrete interferon-gamma (IFN-g), and exert direct killing of tumor cells. In addition, these cells activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response against tumor cells. Gamma delta T-lymphocytes play a key role in the activation of the immune system and do not require major histocompatibility complex (MHC)-mediated antigen presentation to exert their cytotoxic effect.. DNA sequences defined as following: The sequence of nucleotide residues along a DNA chain.. transposase defined as following: Enzymes that recombine DNA segments by a process which involves the formation of a synapse between two DNA helices, the cleavage of single strands from each DNA helix and the ligation of a DNA strand from one DNA helix to the other. The resulting DNA structure is called a Holliday junction which can be resolved by DNA REPLICATION or by HOLLIDAY JUNCTION RESOLVASES.. cellular defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. scRNA-seq defined as following: A procedure that can determine the nucleotide sequence for all of the RNA transcripts in an amplified nucleotide sample that was derived from a single cell.. ATAC-seq defined as following: A molecular genetic technique that isolates and sequences chromosomal regions that are rich in open chromatin. First, nuclei are harvested from a cellular sample. Then a hyperactive Tn5 transposase is added to the nuclei where it excises non-nucleosomal DNA strands and ligates co-administered high-throughput sequencing adapters (tagmentation). The tagged DNA fragments are isolated, amplified by PCR and sequenced. The number of reads for specific region of DNA correlate with increased chromatin accessibility and this method can identify regions of transcription factor and nucleosome binding.. TCR defined as following: The nucleotide-excision repair process that carries out preferential repair of DNA lesions on the actively transcribed strand of the DNA duplex. In addition, the transcription-coupled nucleotide-excision repair pathway is required for the recognition and repair of a small subset of lesions that are not recognized by the global genome nucleotide excision repair pathway. [PMID:10197977, PMID:11900249]. RNAs defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. murine defined as following: Any of numerous species of small rodents belonging to the genus Mus and various related genera of the family Muridae.. ATAC defined as following: Human XCL1 wild-type allele is located in the vicinity of 1q23 and is approximately 5 kb in length. This allele, which encodes lymphotactin protein, is involved in lymphocyte trafficking and inflammatory processes.. human defined as following: Members of the species Homo sapiens..", "label": "yes"} {"id": "converted_1278", "sentence1": "Is there evidence for de novo genesis of enhancers in vertebrates?", "sentence2": "De novo genesis of enhancers in vertebrates., Evolutionary innovation relies partially on changes in gene regulation. While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated. Here we show evidence for the de novo genesis of enhancers in vertebrates. For this, we took advantage of the massive gene loss following the last whole genome duplication in teleosts to systematically identify regions that have lost their coding capacity but retain sequence conservation with mammals. We found that these regions show enhancer activity while the orthologous coding regions have no regulatory activity. These results demonstrate that these enhancers have been de novo generated in fish. By revealing that minor changes in non-regulatory sequences are sufficient to generate new enhancers, our study highlights an important playground for creating new regulatory variability and evolutionary innovation., Here we show evidence for the de novo genesis of enhancers in vertebrates., While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated., While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated, While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated. Here we show evidence for the de novo genesis of enhancers in vertebrates. For this, we took advantage of the massive gene loss following the last whole genome duplication in teleosts to systematically identify regions that have lost their coding capacity but retain sequence conservation with mammals. , Here we show evidence for the de novo genesis of enhancers in vertebrates. , While a growing body of evidence demonstrates that such innovation is generated by functional changes or translocation of regulatory elements via mobile genetic elements, the de novo generation of enhancers from non-regulatory/non-mobile sequences has, to our knowledge, not previously been demonstrated. Here we show evidence for the de novo genesis of enhancers in vertebrates.[SEP]Relations: vertebra has relations: anatomy_anatomy with vertebral element, anatomy_anatomy with vertebral element, anatomy_anatomy with non-transverse process-bearing vertebra, anatomy_anatomy with non-transverse process-bearing vertebra, anatomy_anatomy with vertebral bone 1, anatomy_anatomy with vertebral bone 1, anatomy_anatomy with transverse process-bearing vertebra, anatomy_anatomy with transverse process-bearing vertebra. formation of specialized structure for nutrient acquisition from other organism involved in symbiotic interaction has relations: bioprocess_bioprocess with anatomical structure formation involved in morphogenesis, bioprocess_bioprocess with anatomical structure formation involved in morphogenesis. Definitions: mammals defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. fish defined as following: A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.. vertebrates defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes..", "label": "yes"} {"id": "converted_3829", "sentence1": "Is there any role of genotoxic pks + E. coli in cancer?", "sentence2": "Mutational signature in colorectal cancer caused by genotoxic pks+, Various species of the intestinal microbiota have been associated with the development of colorectal cancer1,2, but it has not been demonstrated that bacteria have a direct role in the occurrence of oncogenic mutations. Escherichia coli can carry the pathogenicity island pks, which encodes a set of enzymes that synthesize colibactin3. This compound is believed to alkylate DNA on adenine residues4,5 and induces double-strand breaks in cultured cells3. Here we expose human intestinal organoids to genotoxic pks+ E. coli by repeated luminal injection over five months. Whole-genome sequencing of clonal organoids before and after this exposure revealed a distinct mutational signature that was absent from organoids injected with isogenic pks-mutant bacteria. The same mutational signature was detected in a subset of 5,876 human cancer genomes from two independent cohorts, predominantly in colorectal cancer. Our study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.[SEP]Relations: malignant colon neoplasm has relations: disease_protein with CHEK2, disease_protein with CHEK2, disease_protein with MYC, disease_protein with MYC, disease_protein with RECK, disease_protein with RECK, disease_protein with APC, disease_protein with APC, disease_protein with NOX4, disease_protein with NOX4. Definitions: luminal defined as following: Relating to the lumen of a blood vessel or other tubular structure.. human defined as following: Members of the species Homo sapiens.. intestinal microbiota defined as following: The collection of microorganisms existing in the intestines of an organism.. adenine defined as following: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. Escherichia coli defined as following: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. bacteria defined as following: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.. cancer defined as following: A malignant tumor at the original site of growth..", "label": "yes"} {"id": "converted_3674", "sentence1": "Thymoquinone is ineffective against radiation induced enteritis, yes or no?", "sentence2": "n this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation. , In this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation., In this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation., TQ might be used for radiation enteritis treatment.[SEP]Relations: intestine has relations: anatomy_protein_present with NOMO3, anatomy_protein_present with NOMO3, anatomy_protein_present with NOMO2, anatomy_protein_present with NOMO2, anatomy_protein_present with MKRN2OS, anatomy_protein_present with MKRN2OS, anatomy_protein_present with NOMO1, anatomy_protein_present with NOMO1, anatomy_protein_present with HOXA-AS3, anatomy_protein_present with HOXA-AS3. Definitions: intestinal defined as following: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.. enteritis defined as following: Inflammation of any segment of the SMALL INTESTINE..", "label": "no"} {"id": "converted_1987", "sentence1": "Is H4K20 methylation associated with DNA replication?", "sentence2": "It seems likely that continued study of the methylation of H4K20 will yield extremely valuable insights concerning the regulation of histone modifications before and during cell division and the impact of these modifications on subsequent gene expression., Aberrant rereplication correlates with decreased levels of H4K20me1 and increased levels of H4K20 trimethylation (H4K20me3)., Consistent with this, H4K20 methylation status plays a direct role in recruiting ORC through the binding properties of ORC1 and ORCA/LRWD1. Thus, coordinating the status of H4K20 methylation is pivotal for the proper selection of DNA replication origins in higher eukaryotes., H4K20 methylation regulates quiescence and chromatin compaction., Mass spectrometry analysis of histone modifications reveals that H4K20me2 and H4K20me3 increase in quiescence and other histone modifications are present at similar levels in proliferating and quiescent cells., Analysis of cells in S, G2/M, and G1 phases shows that H4K20me1 increases after S phase and is converted to H4K20me2 and H4K20me3 in quiescence. , Overexpression of Suv4-20h1, the enzyme that creates H4K20me2 from H4K20me1, results in G2 arrest, consistent with a role for H4K20me1 in mitosis. The results suggest that the same lysine on H4K20 may, in its different methylation states, facilitate mitotic functions in M phase and promote chromatin compaction and cell cycle exit in quiescent cells., Histone H4 lysine 20 methylation: key player in epigenetic regulation of genomic integrity., Intense research during the past few years has revealed histone H4 lysine 20 methylation (H4K20me) as critically important for the biological processes that ensure genome integrity, such as DNA damage repair, DNA replication and chromatin compaction., Disruption of these H4K20-specific histone methyltransferases leads to genomic instability, demonstrating the important functions of H4K20 methylation in genome maintenance. , Both H4K20 mono-methylation and H3K56 acetylation mark transcription-dependent histone turnover in fission yeast., Histone turnover is often associated with various histone modifications such as H3K56 acetylation (H3K56Ac), H3K36 methylation (H3K36me), and H4K20 methylation (H4K20me)., These results together indicate that H4K20me1 as well as H3K56Ac are bona fide marks for transcription-dependent histone turnover in fission yeast., Methylation of histone H4 lysine 20 by PR-Set7 ensures the integrity of late replicating sequence domains in Drosophila., However, these studies were limited to only a handful of mammalian origins, and it remains unclear how PR-Set7 and H4K20 methylation impact the replication program on a genomic scale., The methylation state of lysine 20 on histone H4 (H4K20) has been linked to chromatin compaction, transcription, DNA repair and DNA replication. Monomethylation of H4K20 (H4K20me1) is mediated by the cell cycle-regulated histone methyltransferase PR-Set7, We find that deregulation of H4K20 methylation had no impact on origin activation throughout the genome. Instead, depletion of PR-Set7 and loss of H4K20me1 results in the accumulation of DNA damage and an ATR-dependent cell cycle arrest., We review the signaling pathways and functions associated with a single residue, H4K20, as a model chromatin and clinically important mark that regulates biological processes ranging from the DNA damage response and DNA replication to gene expression and silencing., Thus, coordinating the status of H4K20 methylation is pivotal for the proper selection of DNA replication origins in higher eukaryotes., We employed genetic, cytological, and genomic approaches to better understand the role of PR-Set7 and H4K20 methylation in regulating DNA replication and genome stability in Drosophila cells., The methylation state of lysine 20 on histone H4 (H4K20) has been linked to chromatin compaction, transcription, DNA repair and DNA replication., However, these studies were limited to only a handful of mammalian origins, and it remains unclear how PR-Set7 and H4K20 methylation impact the replication program on a genomic scale., Methylation of histone H4 lysine-20 has been implicated in DNA repair, transcriptional silencing, genomic stability and regulation of replication., Thus, coordinating the status of H4K20 methylation is pivotal for the proper selection of DNA replication origins in higher eukaryotes, Methylation of histone H3 on lysine 79 associates with a group of replication origins and helps limit DNA replication once per cell cycle, We employed genetic, cytological, and genomic approaches to better understand the role of PR-Set7 and H4K20 methylation in regulating DNA replication and genome stability in Drosophila cells., We review the signaling pathways and functions associated with a single residue, H4K20, as a model chromatin and clinically important mark that regulates biological processes ranging from the DNA damage response and DNA replication to gene expression and silencing.**Description:**A polypeptide resulting from the translation of a gene.
. stop codon defined as following: Any codon that signals the termination of genetic translation (TRANSLATION, GENETIC). PEPTIDE TERMINATION FACTORS bind to the stop codon and trigger the hydrolysis of the aminoacyl bond connecting the completed polypeptide to the tRNA. Terminator codons do not specify amino acids.. insertion defined as following: Something inserted or to be inserted.. GUS defined as following: Human GUSB wild-type allele is located in the vicinity of 7q11.21 and is approximately 22 kb in length. This allele, which encodes beta-glucuronidase protein, plays a role in the metabolism of glycosaminoglycans. Mutation of the gene is associated with mucopolysaccharidosis VII.. muscular dystrophy defined as following: A heterogeneous group of inherited MYOPATHIES, characterized by wasting and weakness of the SKELETAL MUSCLE. They are categorized by the sites of MUSCLE WEAKNESS; AGE OF ONSET; and INHERITANCE PATTERNS.. frameshift defined as following: A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.. TBT defined as following: A method for pain relief that uses a breathing technique that focuses on creating sounds..", "label": "yes"} {"id": "converted_3498", "sentence1": "Has ProSavin undergone phase IV clinical trials by 2018?", "sentence2": "Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial., We undertook a phase 1/2 open-label trial with 12-month follow-up at two study sites (France and UK) to assess the safety and efficacy of ProSavin after bilateral injection into the putamen of patients with Parkinson's disease. [SEP]Relations: Parkinson disease has relations: contraindication with Prochlorperazine, contraindication with Prochlorperazine, contraindication with Indomethacin, contraindication with Indomethacin, contraindication with Amikacin, contraindication with Amikacin, contraindication with Rivastigmine, contraindication with Rivastigmine, contraindication with Perphenazine, contraindication with Perphenazine. Definitions: bilateral defined as following: Affecting both sides of the body or a matched pair of organs.. Parkinson's disease defined as following: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75). putamen defined as following: The largest and most lateral of the BASAL GANGLIA lying between the lateral medullary lamina of the GLOBUS PALLIDUS and the EXTERNAL CAPSULE. It is part of the neostriatum and forms part of the LENTIFORM NUCLEUS along with the GLOBUS PALLIDUS..", "label": "no"} {"id": "converted_4236", "sentence1": "Is SMOC2 expressed during wound healing?", "sentence2": "All three fibroblast populations were PDGFRα+/CD34 + but were distinct in their expression of Ngfr/Spon2/Angptl7 (F1), Cxcl14/Smoc2/Rgs2 (F2), and Clec3b/Col14a1/Mmp3 (F3), with potential functions in the regulation of immune responses, response to wounding, and organization of extracellular matrix, respectively., Deficiency of the SMOC2 matricellular protein impairs bone healing and produces age-dependent bone loss.[SEP]Relations: extracellular matrix has relations: cellcomp_protein with SPOCK2, cellcomp_protein with SPOCK2, cellcomp_protein with CPN2, cellcomp_protein with CPN2, cellcomp_protein with SPON2, cellcomp_protein with SPON2, cellcomp_protein with CCN2, cellcomp_protein with CCN2, cellcomp_protein with GFOD2, cellcomp_protein with GFOD2. Definitions: extracellular matrix defined as following: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere..", "label": "yes"} {"id": "converted_2307", "sentence1": "Do cephalopods use RNA editing less frequently than other species?", "sentence2": "Extensive messenger RNA editing generates transcript and protein diversity in genes involved in neural excitability, as previously described, as well as in genes participating in a broad range of other cellular functions, By adopting a method originally designed to detect linkage disequilibrium of DNA mutations, we examined the editomes of ten metazoan species and detected extensive linkage of editing in Drosophila and cephalopods., We here show that RNA editing is particularly common in behaviorally sophisticated coleoid cephalopods, with tens of thousands of evolutionarily conserved sites., Even for the subset of RNA editing sites shared by deeply divergent cephalopod lineages, the primary effect of nuclear editing is an increase-not a decrease-in protein divergence., Coleoid cephalopods (octopus, squid and cuttlefish) are active, resourceful predators with a rich behavioural repertoire., We identified hundreds of cephalopod-specific genes, many of which showed elevated expression levels in such specialized structures as the skin, the suckers and the nervous system., Our analysis suggests that substantial expansion of a handful of gene families, along with extensive remodelling of genome linkage and repetitive content, played a critical role in the evolution of cephalopod morphological innovations, including their large and complex nervous systems.[SEP]Relations: Protein C has relations: drug_drug with Cephaloglycin, drug_drug with Cephaloglycin, drug_drug with Cephalexin, drug_drug with Cephalexin, drug_drug with Cefamandole, drug_drug with Cefamandole, drug_drug with Cefmetazole, drug_drug with Cefmetazole, drug_drug with Cefamandole nafate, drug_drug with Cefamandole nafate. Definitions: genome defined as following: Anatomical set of genes in all the chromosomes.. squid defined as following: A device designed to measure extremely weak magnetic fields. It is comprised of a Josephson junction with two superconducting loops separated by an insulating layer thin enough to allow electrons to pass through.. RNA editing defined as following: A process that changes the nucleotide sequence of mRNA from that of the DNA template encoding it. Some major classes of RNA editing are as follows: 1, the conversion of cytosine to uracil in mRNA; 2, the addition of variable number of guanines at pre-determined sites; and 3, the addition and deletion of uracils, templated by guide-RNAs (RNA, GUIDE, KINETOPLASTIDA).. neural defined as following: Of or relating to neurons or the nervous system.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. cephalopods defined as following: A class in the phylum MOLLUSCA comprised of SQUID; CUTTLEFISH; OCTOPUS; and NAUTILUS. These marine animals are the most highly organized of all the mollusks.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. suckers defined as following: Devices designed for the rapid removal of bulk matter (e.g., vomitus, mucus, debris) from natural or surgical cavities. These tips are usually transparent, short, wide, rigid tubes (either straight or bent) with an integral handle for easy manipulation; the tip is attached to the distal end of suction hoses or tubes that are in turn connected to high-level suction aspirators. Suction tips are used mainly in the upper respiratory tract (nasal cavity and pharynx) and during surgical procedures when suctioning speed rather than control is needed; both reusable and plastic tips are available. Dedicated suction tips are also available for particular procedures performed in the ear, nose, pharynx, and other natural or surgically created cavities. Other hollow-shaft devices such as suction tubes with integral tips, cannulae, curettes, and catheters are also used for suctioning when attached to appropriate aspirators..", "label": "no"} {"id": "converted_2833", "sentence1": "Is LRP1 interacting with Urokinase receptor?", "sentence2": " Interaction with a complex formed by uPA and its inhibitor PAI-1 induces cell surface down regulation and recycling of the receptor via the clathrin-coated pathway, a process dependent on the association to LRP-1., Here we investigated whether direct interaction between uPAR, a glycosyl-phosphatidylinositol-anchored protein, and LRP, a transmembrane receptor,, Direct binding of domain 3 (D3) of uPAR to LRP is required for clearance of uPA-PAI-1-occupied uPAR[SEP]Relations: Urokinase has relations: drug_protein with LRP2, drug_protein with LRP2, drug_protein with SERPINE1, drug_protein with SERPINE1, drug_protein with SERPINA5, drug_protein with SERPINA5, drug_protein with PLG, drug_protein with PLG, drug_protein with MMP12, drug_protein with MMP12. Definitions: LRP-1 defined as following: Prolow-density lipoprotein receptor-related protein 1 (4544 aa, ~505 kDa) is encoded by the human LRP1 gene. This protein is involved in the mediation of endocytosis and turnover.. uPAR defined as following: An extracellular receptor specific for UROKINASE-TYPE PLASMINOGEN ACTIVATOR. It is attached to the cell membrane via a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE and plays a role in the co-localization of urokinase-type plasminogen activator with PLASMINOGEN.. uPA defined as following: A proteolytic enzyme that converts PLASMINOGEN to FIBRINOLYSIN where the preferential cleavage is between ARGININE and VALINE. It was isolated originally from human URINE, but is found in most tissues of most VERTEBRATES.. cell surface defined as following: The external part of the cell wall and/or plasma membrane. [GOC:jl, GOC:mtg_sensu, GOC:sm]. PAI-1 defined as following: A member of the serpin family of proteins. It inhibits both the tissue-type and urokinase-type plasminogen activators.. LRP defined as following: Human RPSA wild-type allele is located in the vicinity of 3p22.2 and is approximately 6 kb in length. This allele, which encodes 40S ribosomal protein SA, plays a role in a variety of biological processes that are mediated by interactions with cell surface receptors.. Urokinase receptor defined as following: An extracellular receptor specific for UROKINASE-TYPE PLASMINOGEN ACTIVATOR. It is attached to the cell membrane via a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE and plays a role in the co-localization of urokinase-type plasminogen activator with PLASMINOGEN..", "label": "yes"} {"id": "converted_4120", "sentence1": "Are Gram positive bacteria able to release extracellular vesicles?", "sentence2": "Gram-negative and Gram-positive bacteria release a variety of membrane vesicles through different formation routes. , Release of extracellular vesicles (EVs) is a common feature among eukaryotes, archaea, and bacteria. However, the biogenesis and downstream biological effects of EVs released from gram-positive bacteria remain poorly characterized., Our findings provide new insight into the role of EVs from gram-positive oral bacteria in periodontal diseases.[SEP]Relations: extracellular vesicle has relations: cellcomp_protein with GRIA4, cellcomp_protein with GRIA4, cellcomp_protein with PRELP, cellcomp_protein with PRELP, cellcomp_protein with RBP3, cellcomp_protein with RBP3, cellcomp_protein with LFNG, cellcomp_protein with LFNG, cellcomp_protein with ARC, cellcomp_protein with ARC. Definitions: archaea defined as following: One of the three domains of life (the others being BACTERIA and Eukarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: (1) the presence of characteristic tRNAs and ribosomal RNAs; (2) the absence of peptidoglycan cell walls; (3) the presence of ether-linked lipids built from branched-chain subunits; and (4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least four kingdoms: CRENARCHAEOTA; EURYARCHAEOTA; NANOARCHAEOTA; and KORARCHAEOTA.. eukaryotes defined as following: Organism or cells with a nucleus separated from the cytoplasm by a two membrance nuclear envelope and compartmentalization of function into distinct cytoplasmic organelles.. extracellular vesicles defined as following: Any vesicle that is part of the extracellular region. [GO_REF:0000064, GOC:pm, GOC:TermGenie, PMID:24769233]. EVs defined as following: The NCI EVS is set of services and resources that address NCI's needs for controlled vocabulary. The EVS Project is a collaborative effort of the Center for Bioinformatics and the NCI Office of Communications. The NCI Thesaurus, which is a biomedical thesaurus created specifically to meet the needs of the NCI, is produced by the NCI EVS project. The NCI Thesaurus is provided under an open content license. The EVS Project also produces the NCI Metathesaurus, which is based on NLM's Unified Medical Language System Metathesaurus supplemented with additional cancer-centric vocabulary. In addition the EVS Project provides NCI with licenses for MedDRA, SNOMED, ICD-O-3, and other proprietary vocabularies.. bacteria defined as following: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive..", "label": "yes"} {"id": "converted_393", "sentence1": "Is there an association between bruxism and reflux?", "sentence2": "Sleep bruxism is prevalent in GERD patients, and GERD is highly associated with SB., There was a statistical trend towards tooth wear progression being associated with gastric risk factors (p < 0.05). , This article presents a case report of a 27-year-old male smoker with tooth wear and dentin sensitivity caused by GERD associated with bruxism. , The aim of this cross-over, randomized, single-blinded trial was to examine whether intra-esophageal acidification induces sleep bruxism (SB). , RMMA episodes including SB were induced by esophageal acidification. , Chronic regurgitation of gastric acids in patients with gastroesophageal reflux disease may cause dental erosion, which can lead in combination with attrition or bruxism to extensive loss of coronal tooth tissue., This clinical report describes treatment of severe tooth wear of a gastroesophageal reflux disease patient who is 54-year-old Turkish male patient. After his medical treatment, severe tooth wear, bruxism and decreased vertical dimensions were determined. , Gastroesophageal reflux disease by itself or in combination with attrition, abrasion or bruxism may be responsible for the loss., The association between bruxism, feeding and smoking habits and digestive disorders may lead to serious consequences to dental and related structures, involving dental alterations (wear, fractures and cracks), periodontal signs (gingival recession and tooth mobility) and muscle-joint sensitivity, demanding a multidisciplinary treatment plan. This paper presents a case report in which bruxism associated with acid feeding, smoking habit and episodes of gastric reflow caused severe tooth wear and great muscular discomfort with daily headache episodes. , The frequencies of RMMA, single short-burst, and clenching episodes were significantly higher during decreased esophageal pH episodes than those during other times. , These results suggest that most jaw muscle activities, ie, RMMA, single short-burst, and clenching episodes, occur in relation to gastroesophageal reflux mainly in the supine position., Nocturnal bruxism may be secondary to nocturnal gastroesophageal reflux, occurring via sleep arousal and often together with swallowing.[SEP]Relations: Gastroesophageal reflux has relations: disease_phenotype_positive with Joubert syndrome with Jeune asphyxiating thoracic dystrophy, disease_phenotype_positive with Joubert syndrome with Jeune asphyxiating thoracic dystrophy, disease_phenotype_positive with citrullinemia, disease_phenotype_positive with citrullinemia, disease_phenotype_positive with atrioventricular defect-blepharophimosis-radial and anal defect syndrome, disease_phenotype_positive with atrioventricular defect-blepharophimosis-radial and anal defect syndrome. gastroesophageal reflux disease has relations: contraindication with Racementhol, contraindication with Racementhol, contraindication with Butabarbital, contraindication with Butabarbital. Definitions: gastroesophageal reflux defined as following: Effortless regurgitation of gastric contents that commonly occurs in infants, usually right after feeding or burping.. gastric acids defined as following: Hydrochloric acid present in GASTRIC JUICE.. headache defined as following: The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.. digestive disorders defined as following: Diseases in any part of the GASTROINTESTINAL TRACT or the accessory organs (LIVER; BILIARY TRACT; PANCREAS).. tooth mobility defined as following: Horizontal and, to a lesser degree, axial movement of a tooth in response to normal forces, as in occlusion. It refers also to the movability of a tooth resulting from loss of all or a portion of its attachment and supportive apparatus, as seen in periodontitis, occlusal trauma, and periodontosis. (From Jablonski, Dictionary of Dentistry, 1992, p507 & Boucher's Clinical Dental Terminology, 4th ed, p313). tooth wear defined as following: Loss of the tooth substance by chemical or mechanical processes. muscular defined as following: One of the contractile organs of the body.. sleep bruxism defined as following: A sleep disorder characterized by grinding and clenching of the teeth and forceful lateral or protrusive jaw movements. Sleep bruxism may be associated with TOOTH INJURIES; TEMPOROMANDIBULAR JOINT DISORDERS; sleep disturbances; and other conditions.. gastroesophageal reflux disease defined as following: Retrograde flow of gastric juice (GASTRIC ACID) and/or duodenal contents (BILE ACIDS; PANCREATIC JUICE) into the distal ESOPHAGUS, commonly due to incompetence of the LOWER ESOPHAGEAL SPHINCTER.. bruxism defined as following: A disorder characterized by grinding and clenching of the teeth.. fractures defined as following: A traumatic injury to the bone in which the continuity of the bone is broken.. esophageal defined as following: Of or relating to the esophagus.. reflux defined as following: An abnormal backward flow of a body fluid..", "label": "yes"} {"id": "converted_1216", "sentence1": "Can desvenlafaxine be used at a dose of 50mg/day?", "sentence2": "Long-term use of desvenlafaxine was safe and well tolerated, with a clinical benefit/risk profile similar to that in other populations., e objective of this study was to evaluate the long-term safety of desvenlafaxine for continuation treatment of major depressive disorder (MDD) in Japanese patients. This was a phase 3, multicenter, 10-month, open-label study with flexible dosing of desvenlafaxine (25, 50, 100 mg/day), n an effort to establish the lowest effective dose of desvenlafaxine (administered as desvenlafaxine succinate), we assessed the efficacy, safety, and tolerability of 10- and 50-mg/day desvenlafaxine vs placebo for the treatment of major depressive disorder, Change from baseline to final evaluation in adjusted HAM-D(17) total scores was not significantly different comparing desvenlafaxine 10 mg/day (-9.28) and desvenlafaxine 50 mg/day (-8.92) with placebo (-8.42), Overall rates of treatment-emergent adverse events with both doses were similar to placebo, However, in a companion study reported separately, desvenlafaxine 50 mg, but not 25 mg, separated from placebo. Taken together, these studies suggest that 50 mg is the minimum effective dose of desvenlafaxine for the treatment of major depressive disorder. , Desvenlafaxine XR was dosed at 50 mg/day for 10 days., Desvenlafaxine therapy is initiated at the therapeutic dose (50 mg/day) without a need for dose titration., Clinical studies have investigated the efficacy of DVS in doses ranging from 50 to 400 mg/day for the treatment of MDD in adult outpatients. The effects of DVS 50 mg/day have been clearly distinguished from placebo in the reduction of MDD symptoms in such clinical trials. No additional therapeutic benefits were found at doses > 50 mg/day. The recommended dose of DVS ranges from 50 to 100 mg., Adult outpatients with major depressive disorder received desvenlafaxine doses ranging from 50-400 mg/day or placebo for 8 weeks, At the recommended therapeutic dose of 50 mg/day, discontinuation due to adverse events was similar to placebo, atients received fixed (50, 100, 200, or 400 mg/day; n=1,342) or flexible doses (100-400 mg/day; n=463) of desvenlafaxine or placebo (n=1,108), Desvenlafaxine demonstrated short-term efficacy for treating major depressive disorder across the range of doses studied. No evidence of greater efficacy was observed with doses >50 mg/day; a strong dose-response effect on tolerability was observed., To assess the efficacy, safety, and tolerability of 50- and 100-mg/day doses of desvenlafaxine (administered as desvenlafaxine succinate), a serotonin-norepinephrine reuptake inhibitor, for the treatment of major depressive disorder (MDD), Patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) MDD and 17-item Hamilton Rating Scale for Depression (HAM-D(17)) scores > or =20 were randomly assigned to double-blind placebo or desvenlafaxine treatment (fixed dose of 50 mg/day or 100 mg/day) for 8 weeks., Desvenlafaxine 50 mg was associated with a significantly greater adjusted mean change from baseline on the HAM-D(17) (-11.5) compared with placebo (-9.5, p=0.018), These results demonstrate efficacy, safety, and tolerability of desvenlafaxine 50 mg/day for treating MDD. , CONCLUSIONS: Desvenlafaxine at the recommended dose of 50 mg/d was effective in relapse prevention of depression during a 6-month period in patients who demonstrated stable response after 20 weeks of open-label desvenlafaxine treatment.[SEP]Relations: Desvenlafaxine has relations: drug_drug with Dosulepin, drug_drug with Dosulepin, drug_drug with Colistimethate, drug_drug with Colistimethate, drug_drug with Etonogestrel, drug_drug with Etonogestrel, drug_drug with Nomifensine, drug_drug with Nomifensine, drug_drug with Pemetrexed, drug_drug with Pemetrexed. Definitions: Desvenlafaxine defined as following: A synthetic phenethylamine bicyclic derivative with antidepressant activity. Desvenlafaxine is a selective reuptake inhibitor of serotonin and norepinephrine due to its high binding affinities to the pre-synaptic serotonin and norepinephrine transporters. By blocking both transporters, this agent prolongs neurotransmitter activities of both serotonin and norepinephrine, thereby alleviating depressive state.. MDD defined as following: Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5). mg/day defined as following: A unit of mass flow rate equivalent to the rate at which one thousandth of a gram of matter crosses a given surface or is delivered to a given object or space over a period of time equal to twenty four hours. Milligram per twenty four hours is also a dose administration rate unit equal to the rate at which one thousandth of a gram of a product is administered per unit of time equal to twenty four hours.. desvenlafaxine defined as following: A synthetic phenethylamine bicyclic derivative with antidepressant activity. Desvenlafaxine is a selective reuptake inhibitor of serotonin and norepinephrine due to its high binding affinities to the pre-synaptic serotonin and norepinephrine transporters. By blocking both transporters, this agent prolongs neurotransmitter activities of both serotonin and norepinephrine, thereby alleviating depressive state..", "label": "yes"} {"id": "converted_2931", "sentence1": "Are Mesenchymal stem cells (MSC) multipotent cells?", "sentence2": "multipotent mesenchymal bone marrow-derived stem cells, multipotent hESC-derived mesenchymal cells (MCs)[SEP]Relations: intellectual developmental disorder has relations: disease_phenotype_positive with Macrocephaly, disease_phenotype_positive with Macrocephaly, disease_phenotype_positive with Generalized myoclonic-atonic seizure, disease_phenotype_positive with Generalized myoclonic-atonic seizure, disease_phenotype_positive with Smooth philtrum, disease_phenotype_positive with Smooth philtrum, disease_phenotype_positive with Long palpebral fissure, disease_phenotype_positive with Long palpebral fissure, disease_phenotype_positive with Striae distensae, disease_phenotype_positive with Striae distensae. Definitions: MSC defined as following: A naturally occurring organoselenium compound found in many plants, including garlic, onions, and broccoli, with potential antioxidant and chemopreventive activities. Se-Methyl-seleno-L-cysteine (MSC) is an amino acid analogue of cysteine in which a methylselenium moiety replaces the sulphur atom of cysteine. This agent acts as an antioxidant when incorporated into glutathione peroxidase and has been shown to exhibit potent chemopreventive activity in animal models.. Mesenchymal stem cells defined as following: An undifferentiated stromal cell with the ability to develop into the cells that form distinct mesenchymal tissues; such as bone, muscle, connective tissue, blood vessels, and lymphatic tissue..", "label": "yes"} {"id": "converted_3965", "sentence1": "Is co-loss of BRCA2-RB1 associated with better prognosis for prostate cancer patients?", "sentence2": "In human prostate cancer cell lines (LNCaP and LAPC4), loss of BRCA2 leads to the castration-resistant phenotype. Co-loss of BRCA2-RB1 in human prostate cancer cells induces an epithelial-to-mesenchymal transition, which is associated with invasiveness and a more aggressive disease phenotype. Importantly, PARP inhibitors attenuate cell growth in human mCRPC-derived organoids and human CRPC cells harboring single-copy loss of both genes.CONCLUSIONS: Our findings suggest that early identification of this aggressive form of prostate cancer offers potential for improved outcomes with early introduction of PARP inhibitor-based therapy.[SEP]Relations: benign neoplasm of prostate has relations: disease_disease with prostatic adenoma, disease_disease with prostatic adenoma, disease_disease with fibroma of prostate, disease_disease with fibroma of prostate, disease_disease with prostate leiomyoma, disease_disease with prostate leiomyoma, disease_disease with benign prostate phyllodes tumor, disease_disease with benign prostate phyllodes tumor, disease_disease with prostate neoplasm, disease_disease with prostate neoplasm. Definitions: prostate cancer defined as following: A primary or metastatic malignant tumor involving the prostate gland. The vast majority are carcinomas.. PARP defined as following: Human PARP1 wild-type allele is located within 1q41-q42 and is approximately 47 kb in length. This allele, which encodes poly [ADP-ribose] polymerase 1 protein, plays a critical role in DNA repair.. human defined as following: Members of the species Homo sapiens.. BRCA2 defined as following: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. Mutations in this gene predispose humans to breast and ovarian cancer. It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev 2000;14(11):1400-6). genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "no"} {"id": "converted_4560", "sentence1": "Is serotonin transported by platelets?", "sentence2": " activated platelets, which carry peripheral serotonin,, Platelet serotonin response was measured by serotonin augmented platelet aggregation and platelet serotonin receptor density. , SERT was studied in the 1970s and 1980s using membrane vesicles isolated from blood platelets., platelet-dense granules contain neurotransmitters such as serotonin and gamma-aminobutyric acid. Molecular players controlling granule formation and secretion are, Platelets transport and store virtually all plasma serotonin in dense granules[SEP]Relations: Serotonin has relations: drug_drug with Sarpogrelate, drug_drug with Sarpogrelate, drug_drug with Ketamine, drug_drug with Ketamine, drug_drug with Pargyline, drug_drug with Pargyline, drug_drug with Saredutant, drug_drug with Saredutant, drug_drug with Piperidolate, drug_drug with Piperidolate. Definitions: platelets defined as following: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.. gamma-aminobutyric acid defined as following: The most common inhibitory neurotransmitter in the central nervous system.. serotonin defined as following: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator..", "label": "yes"} {"id": "converted_222", "sentence1": "Is there any association between Jarid2 and miR-155 in Th17 cells?", "sentence2": "Jarid2 links MicroRNA and chromatin in Th17 cells., In this issue of Immunity, Escobar et al. (2014) bring microRNAs and chromatin together by showing how activation-induced miR-155 targets the chromatin protein Jarid2 to regulate proinflammatory cytokine production in T helper 17 cells., miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression., Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation. miR-155-deficient Th17 and T regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin. PRC2 binding to chromatin and H3K27 histone methylation was increased in miR-155-deficient cells, coinciding with failure to express Il22, Il10, Il9, and Atf3. Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2., Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2., Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2., Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2., Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.[SEP]Relations: MIR155 has relations: disease_protein with lung cancer, disease_protein with lung cancer, disease_protein with lung neoplasm, disease_protein with lung neoplasm, bioprocess_protein with negative regulation of gene expression, bioprocess_protein with negative regulation of gene expression, disease_protein with goblet cell carcinoma, disease_protein with goblet cell carcinoma, disease_protein with carcinoid tumor (disease), disease_protein with carcinoid tumor (disease). Definitions: Th17 cells defined as following: A subset of helper-effector T-lymphocytes which synthesize and secrete INTERLEUKINS IL-17; IL-17F; and IL-22. These cytokines are involved in host defenses and tissue inflammation in autoimmune diseases.. Polycomb Repressive Complex 2 defined as following: A multisubunit polycomb protein complex that catalyzes the METHYLATION of chromosomal HISTONE H3. It works in conjunction with POLYCOMB REPRESSIVE COMPLEX 1 to effect EPIGENETIC REPRESSION.. Il22 defined as following: Interleukin-22 (179 aa, ~20 kDa) is encoded by the human IL22 gene. This protein is involved in both cell signaling and the immune response.. Mir155 defined as following: This gene is involved in the regulation of gene expression and plays a potential tumor suppressor role in breast and pancreatic carcinomas, acute lymphoblastic leukemia and diffuse large B-cell lymphoma.. cytokine defined as following: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.. microRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. Atf3 defined as following: Cyclic AMP-dependent transcription factor ATF-3 (181 aa, ~21 kDa) is encoded by the human ATF3 gene. This protein plays a role in both DNA binding and the repression of gene expression.. Il10 defined as following: A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.. Treg cell defined as following: CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.. Il9 defined as following: A multifunctional cytokine secreted by primarily by activated TH2 CELLS that may play a role as a regulator of allergic INFLAMMATION. It has been shown to enhance the growth and CELL DIFFERENTIATION of MAST CELLS, and can act on a variety of other immune cells.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. DNA-binding protein defined as following: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary..", "label": "yes"} {"id": "converted_525", "sentence1": "Are BBS mutations involved in syndromic Hirschsprung disease?", "sentence2": "Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease, Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays. Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease, Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease., Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease., Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays, Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease, Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays[SEP]Relations: hirschsprung disease, susceptibility to has relations: disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance, disease_protein with MED12, disease_protein with MED12, disease_protein with EDNRB, disease_protein with EDNRB, disease_protein with GDNF, disease_protein with GDNF, disease_protein with RET, disease_protein with RET. Definitions: RET defined as following: a unit of radiation dose. BBS defined as following: An autosomal recessive disorder characterized by RETINITIS PIGMENTOSA; POLYDACTYLY; OBESITY; MENTAL RETARDATION; hypogenitalism; renal dysplasia; and short stature. This syndrome has been distinguished as a separate entity from LAURENCE-MOON SYNDROME. (From J Med Genet 1997 Feb;34(2):92-8). mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"} {"id": "converted_2626", "sentence1": "Can nanoparticles be used for afterglow imaging?", "sentence2": "Ultralong Phosphorescence of Water-Soluble Organic Nanoparticles for In Vivo Afterglow Imaging, Afterglow or persistent luminescence eliminates the need for light excitation and thus circumvents the issue of autofluorescence, holding promise for molecular imaging. However, current persistent luminescence agents are rare and limited to inorganic nanoparticles. This study reports the design principle, synthesis, and proof-of-concept application of organic semiconducting nanoparticles (OSNs) with ultralong phosphorescence for in vivo afterglow imaging. , This study not only introduces the first category of water-soluble ultralong phosphorescence organic nanoparticles but also reveals a universal design principle to prolong the lifetime of phosphorescent molecules to the level that can be effective for molecular imaging.[SEP]Relations: inorganic anion transport has relations: bioprocess_protein with NMUR2, bioprocess_protein with NMUR2, bioprocess_protein with SLC4A7, bioprocess_protein with SLC4A7, bioprocess_protein with SLC4A5, bioprocess_protein with SLC4A5, bioprocess_protein with SLC22A6, bioprocess_protein with SLC22A6, bioprocess_protein with VDAC1, bioprocess_protein with VDAC1. Definitions: inorganic defined as following: Relating or belonging to the class of compounds not having a carbon basis.. nanoparticles defined as following: Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging..", "label": "yes"} {"id": "converted_4256", "sentence1": "Is esophageal adenocarcinoma associated with aberrant glycosylation?", "sentence2": "Altered glycoprotein expression has been demonstrated in tissue from patients with Barrett's esophagus and esophageal cancer but the mechanisms regarding such changes are unknown. , Esophageal adenocarcinoma represents a highly morbid and mortal cancer with a defined progression from metaplasia (Barrett's esophagus) to dysplasia to neoplasia. This disease is highlighted because (1) differences in glycan profiles between the stages of disease progression have been described in the glycoproteomic literature; (2) a glycan biomarker that identifies a given stage may be used as a predictor of disease progression and thus may have significant influence over clinical management; and (3) the differences in glycan profiles between disease and disease-free states in esophageal cancer are more dramatic than in other cancers., comparative glycomic profiling of EAC reveals a subset of glycans that can be selected as candidate biomarkers, comparative glycomic profiling of esophageal adenocarcinoma reveals a subset of glycans that can be selected as candidate biomarkers, IgG glycosylation profile was independently associated with esophageal precancerosis beyond inflammation, which could be an early biomarker for esophageal cancer.[SEP]Relations: carcinoma of esophagus has relations: disease_protein with GHRL, disease_protein with GHRL, disease_protein with GNG7, disease_protein with GNG7, disease_disease with esophageal adenosquamous carcinoma, disease_disease with esophageal adenosquamous carcinoma, disease_protein with SST, disease_protein with SST, disease_protein with EGFR, disease_protein with EGFR. Definitions: IgG defined as following: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.. esophageal adenocarcinoma defined as following: A malignant tumor with glandular differentiation arising predominantly from Barrett mucosa in the lower third of the esophagus. Rare examples of esophageal adenocarcinoma deriving from ectopic gastric mucosa in the upper esophagus have also been reported. Grossly, esophageal adenocarcinomas are similar to esophageal squamous cell carcinomas. Microscopically, adenocarcinomas arising in the setting of Barrett esophagus are typically papillary and/or tubular. The prognosis is poor.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. metaplasia defined as following: A condition in which there is a change of one adult cell type to another similar adult cell type.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. neoplasia defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. esophageal cancer defined as following: A primary or metastatic malignant neoplasm involving the esophagus.. glycoprotein defined as following: Conjugated protein-carbohydrate compounds including MUCINS; mucoid, and AMYLOID glycoproteins.. Barrett's esophagus defined as following: A condition with damage to the lining of the lower ESOPHAGUS resulting from chronic acid reflux (ESOPHAGITIS, REFLUX). Through the process of metaplasia, the squamous cells are replaced by a columnar epithelium with cells resembling those of the INTESTINE or the salmon-pink mucosa of the STOMACH. Barrett's columnar epithelium is a marker for severe reflux and precursor to ADENOCARCINOMA of the esophagus.. dysplasia defined as following: A usually neoplastic transformation of the cell, associated with altered architectural tissue patterns. The cellular changes include nuclear and cytoplasmic abnormalities. Molecular genetic abnormalities are also often found and, in some instances, may lead to cancer.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown..", "label": "yes"} {"id": "converted_1595", "sentence1": "Does TRIM37 gene mutation causes Mulibrey nanism?", "sentence2": "OBJECTIVE: We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene., In MUL, mutations in TRIM37 lead to disturbance of sexual maturation, and fertility is severely compromised. , It is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin-ligase activity. , Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function. , Gynecological tumors in Mulibrey nanism and role for RING finger protein TRIM37 in the pathogenesis of ovarian fibrothecomas., To investigate the possible involvement of TRIM37 alterations in the pathogenesis of sporadic fibrothecomas, we analyzed the TRIM37 cDNA for mutations and alternatively spliced transcripts and TRIM37 expression in fibrothecomas of women without Mulibrey nanism. , In conclusion, inherited biallelic inactivation of TRIM37 (Mulibrey nanism) predisposes to both mesenchymal and epithelial ovarian tumors and dysregulation of TRIM37 may also be involved in the pathogenesis of sporadic fibrothecomas., A novel splice site mutation in the TRIM37 gene causes mulibrey nanism in a Turkish family with phenotypic heterogeneity., Mulibrey nanism (MUL) is an autosomal recessive disease caused by mutations in the TRIM37 gene encoding the peroxisomal TRIM37 protein of unknown function., Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene., Mutations in the TRIM37 gene underlie mulibrey nanism (muscle-liver-brain-eye nanism), a rare monogenic developmental disorder characterized by severe growth failure, characteristic dysmorphic features, cardiopathy, failure of sexual maturation, and metabolic syndrome., Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function., Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein., Novel mutations in the TRIM37 gene in Mulibrey Nanism., Five truncating mutations in the TRIM37 gene have previously been reported in Mulibrey nanism patients., Characterisation of the mulibrey nanism-associated TRIM37 gene: transcription initiation, promoter region and alternative splicing., The TRIM37 gene encodes a peroxisomal RING-B-box-coiled-coil protein: classification of mulibrey nanism as a new peroxisomal disorder., A novel splice site mutation in the TRIM37 gene causes mulibrey nanism in a Turkish family with phenotypic heterogeneity, Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein, Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene, Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function, Mulibrey nanism (MUL) is an autosomal recessive disease caused by mutations in the TRIM37 gene encoding the peroxisomal TRIM37 protein of unknown function, Novel mutations in the TRIM37 gene in Mulibrey Nanism, Five truncating mutations in the TRIM37 gene have previously been reported in Mulibrey nanism patients, Mulibrey nanism (MUL) is a rare autosomal recessive disorder with severe primordial growth retardation and multiorgan involvement, caused by mutations in TRIM37, Refractory congestive heart failure following delayed pericardectomy in a 12-year-old child with Mulibrey nanism due to a novel mutation in TRIM37, A novel mutation in TRIM37 is associated with mulibrey nanism in a Turkish boy, OBJECTIVE: We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene. , Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein. , Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene. , UNLABELLED: Mulibrey nanism (MUL) is a rare autosomal recessive disorder with severe primordial growth retardation and multiorgan involvement, caused by mutations in TRIM37. , Mulibrey nanism (MUL) is an autosomal recessive disease caused by mutations in the TRIM37 gene encoding the peroxisomal TRIM37 protein of unknown function. , Mutations in TRIM37 underlie mulibrey nanism, a rare autosomal recessively inherited disorder with severe growth failure of prenatal onset, constrictive pericardium, hepatomegaly and characteristic dysmorphic features. , Mutations in the TRIM37 gene underlie mulibrey nanism (muscle-liver-brain-eye nanism), a rare monogenic developmental disorder characterized by severe growth failure, characteristic dysmorphic features, cardiopathy, failure of sexual maturation, and metabolic syndrome., A novel mutation in TRIM37 is associated with mulibrey nanism in a Turkish boy., Five truncating mutations in the TRIM37 gene have previously been reported in Mulibrey nanism patients., Few monogenic mutations causing human male infertility have been identified to date. We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene., Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein. The pathogenetic mechanisms of mulibrey nanism are unknown., Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function. More than half of female patients with Mulibrey nanism develop benign mesenchymal tumors of ovarian sex cord-stromal origin., Mulibrey nanism (MUL) is an autosomal recessive disease caused by mutations in the TRIM37 gene encoding the peroxisomal TRIM37 protein of unknown function., Mulibrey nanism (muscle-liver-brain-eye nanism; MUL) is an autosomal recessively transmitted disease characterized by severe growth delays of prenatal onset caused by mutations in the TRIM37 gene., Mulibrey nanism (MUL) is a monogenic disorder with prenatal-onset growth failure, typical clinical characteristics, cardiopathy and tendency for a metabolic syndrome. It is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin-ligase activity., We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene. Twenty-eight male MUL patients of the Finnish national cohort aged 8.7 to 50.0 yr (median age, 28.8) at the end of observation were followed for 10 yr beginning from 2000-2001., A novel splice site mutation in the TRIM37 gene causes mulibrey nanism in a Turkish family with phenotypic heterogeneity., We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene., Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function., Mulibrey nanism is a rare growth disorder of prenatal onset caused by mutations in the TRIM37 gene, which encodes a RING-B-box-coiled-coil protein., Novel mutations in the TRIM37 gene in Mulibrey Nanism., Five truncating mutations in the TRIM37 gene have previously been reported in Mulibrey nanism patients., It is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin-ligase activity., Mulibrey nanism (MUL) is a rare autosomal recessive disorder with severe primordial growth retardation and multiorgan involvement, caused by mutations in TRIM37.[SEP]Relations: mulibrey nanism has relations: disease_protein with TRIM37, disease_protein with TRIM37, disease_disease with autosomal recessive disease, disease_disease with autosomal recessive disease, disease_phenotype_positive with Autosomal recessive inheritance, disease_phenotype_positive with Autosomal recessive inheritance, disease_disease with syndromic disease, disease_disease with syndromic disease, disease_phenotype_positive with Macrocephaly, disease_phenotype_positive with Macrocephaly. Definitions: autosomal recessive disorder defined as following: An inherited disorder manifested only when two copies of a mutated gene are present.. hepatomegaly defined as following: Enlargement of the liver.. TRIM37 defined as following: E3 ubiquitin-protein ligase TRIM37 (964 aa, ~108 kDa) is encoded by the human TRIM37 gene. This protein plays a role in centriole replication inhibition.. MUL defined as following: Human TRIM37 wild-type allele is located in the vicinity of 17q22 and is approximately 139 kb in length. This allele, which encodes E3 ubiquitin-protein ligase TRIM37 protein, is involved in chromatin modification and centriole replication. Mutation of the gene is associated with mulibrey nanism.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. cardiopathy defined as following: Pathological conditions involving the HEART including its structural and functional abnormalities.. human defined as following: Members of the species Homo sapiens.. peroxisomal disorder defined as following: A heterogeneous group of inherited metabolic disorders marked by absent or dysfunctional PEROXISOMES. Peroxisomal enzymatic abnormalities may be single or multiple. Biosynthetic peroxisomal pathways are compromised, including the ability to synthesize ether lipids and to oxidize long-chain fatty acid precursors. Diseases in this category include ZELLWEGER SYNDROME; INFANTILE REFSUM DISEASE; rhizomelic chondrodysplasia (CHONDRODYSPLASIA PUNCTATA, RHIZOMELIC); hyperpipecolic acidemia; neonatal adrenoleukodystrophy; and ADRENOLEUKODYSTROPHY (X-linked). Neurologic dysfunction is a prominent feature of most peroxisomal disorders.. transcripts defined as following: The initial RNA molecule produced by transcription.. metabolic syndrome defined as following: A combination of medical conditions that when present, increase the risk of heart attack, stroke, and diabetes mellitus. It includes the following medical conditions: increased blood pressure, central obesity, dyslipidemia, impaired glucose tolerance, and insulin resistance.. promoter region defined as following: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. muscle-liver-brain-eye nanism defined as following: An autosomal recessive inherited disorder caused by mutations in the TRIM37 gene. It is characterized by marked growth retardation and abnormalities in multiple organs including heart, liver, muscle, eyes, and brain.. Refractory defined as following: Not responding to treatment.. RING-B-box-coiled-coil protein defined as following: This gene plays a role in protein ubiquitination, transcriptional regulation and regulation of centriole replication.. autosomal defined as following: Any chromosome other than a sex chromosome. [GOC:mah]. congestive heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs..", "label": "yes"} {"id": "converted_1465", "sentence1": "Does triiodothyronine (T3) has cardiac angiogenic effects?", "sentence2": "T3-induced cardiac sprouting angiogenesis in adult hypothyroid mice was associated with PDGF-BB, PDGFR-β and downstream activation of Akt., L-T3 significantly increased angiogenesis and cell survival and enhanced the expression of nuclear-encoded transcription factors involved in these processes., T(3) administration restored TRbeta mRNA expression level in AAC hearts to the control level., Rbeta knockout and TRalpha/TRbeta double-knockout mice both exhibited significantly less capillary density in LV compared with wild-type mice., TRbeta in the coronary ECs regulates capillary density during cardiac development, and down-regulation of TRbeta results in coronary microvascular rarefaction during pathological hypertrophy.[SEP]Relations: Liothyronine has relations: contraindication with sudden cardiac arrest, contraindication with sudden cardiac arrest, contraindication with cardiovascular disease, contraindication with cardiovascular disease, drug_effect with Tachycardia, drug_effect with Tachycardia, drug_effect with Arrhythmia, drug_effect with Arrhythmia, drug_effect with Congestive heart failure, drug_effect with Congestive heart failure. Definitions: TRbeta defined as following: This gene plays a role in receptor signaling and regulation of transcription. It is involved in inner ear development and color vision.. Akt defined as following: Expressed in diverse tissues, Protein Kinase B (AKT/RAC Family) is a group (Alpha, Beta and Gamma) of cytoplasmic serine/threonine enzymes that covalently transfer the terminal, gamma phosphate group from ATP to a variety of substrate proteins and regulate cell signaling responses to insulin, PDGF, and IGF1 (through PI3K) involved in cell survival, cell proliferation, differentiation, apoptosis, glycogen synthesis, and glucose uptake.. L-T3 defined as following: A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.. PDGF-BB defined as following: The recombinant analog of endogenous beta (B) chain of the cytokine platelet-derived growth factor (PDGF). Synthesized primarily by megakaryocytes, endogenous PDGF consists of two related peptide chains, PDGF-A and PDGF-B. PDGF functions as a local autocrine and paracrine growth factor in many cellular processes. Recombinant PDGF, alone and in combination with other agents, may be useful in promoting bone formation and soft tissue repair. (NCI04). triiodothyronine defined as following: A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.. T3 defined as following: This gene plays a regulatory role in the production and utilization of ATP..", "label": "yes"} {"id": "converted_1559", "sentence1": "Are the proteins Erbin (LAP2) and Merlin cooperating?", "sentence2": "Erbin and the NF2 tumor suppressor Merlin cooperatively regulate cell-type-specific activation of PAK2 by TGF-beta., The results show that the epithelial-enriched protein Erbin controls the function of the NF2 tumor suppressor Merlin by determining the output of Merlin's physical interactions with active PAK2. , Erbin controls Merlin tumor suppressor function by switching the functional valence of PAK2 binding[SEP]Relations: protein insertion into ER membrane has relations: bioprocess_protein with TRAM2, bioprocess_protein with TRAM2, bioprocess_protein with CYB5A, bioprocess_protein with CYB5A, bioprocess_protein with ALDH3A2, bioprocess_protein with ALDH3A2, bioprocess_protein with UBE2J2, bioprocess_protein with UBE2J2, bioprocess_protein with VAMP2, bioprocess_protein with VAMP2. Definitions: TGF-beta defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine transforming growth factor-beta (TGF-beta) with proapoptotic and antineoplastic properties. TGF-beta may suppress tumor cell growth by decreasing the expression of cyclin D1, a cell cycle regulatory protein, and downregulating the expression of the oncogene c-myc. This agent is also involved in T cell-mediated immunosuppression by CD4+CD25+ T cells, which permits cancer cells to evade immune surveillance. (NCI04). Erbin defined as following: Protein LAP2 (1412 aa, ~158 kDa) is encoded by the human ERBIN gene. This protein plays a role in the modulation of receptor tyrosine kinase signaling.. Merlin defined as following: A membrane protein homologous to the ERM (Ezrin-Radixin-Moesin) family of cytoskeleton-associated proteins which regulate physical properties of membranes. Alterations in neurofibromin 2 are the cause of NEUROFIBROMATOSIS 2.. LAP2 defined as following: Human HSP90AA1 wild-type allele is located in the vicinity of 14q32.33 and is approximately 59 kb in length. This allele, which encodes heat shock protein HSP 90-alpha, plays a role in both nitric oxide metabolism and protein folding. A chromosomal translocation t(3;14)(q27;q32) of this gene and the BCL6 gene is associated with B cell non-Hodgkin lymphoma..", "label": "yes"} {"id": "converted_4331", "sentence1": "Are Epoxyeicosatrienoic acids (EETs) synthesized by cytochrome P450 epoxygenases from arachidonic acid?", "sentence2": "Biologically active epoxyeicosatrienoic acid (EET) regioisomers are synthesized from arachidonic acid by cytochrome P450 epoxygenases of endothelial, myocardial, and renal tubular cells., epoxyeicosatrienoic acids (EETs), synthesized by cytochrome P450 epoxygenases from arachidonic acid. , Epoxyeicosatrienoic acids (EETs), synthesized from arachidonic acid by cytochrome P450 epoxygenases, Epoxyeicosatrienoic acids (EETs), which are synthesized from arachidonic acid by cytochrome P450 epoxygenases, function primarily as autocrine and paracrine effectors in the cardiovascular system and kidney. , Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by cytochrome P450 epoxygenases in endothelial cells. I, Epoxyeicosatrienoic acids (EETs), the eicosanoid biomediators synthesized from arachidonic acid by cytochrome P450 epoxygenases,, Epoxyeicosatrienoic acids (EETs) are bioactive eicosanoids produced from arachidonic acid by cytochrome P450 epoxygenases., Arachidonic acid is metabolized to epoxyeicosatrienoic acids (EETs) by cytochrome (CYP) P450 epoxygenases, and to ω-terminal hydroxyeicosatetraenoic acids (HETEs) by ω-hydroxylases., Epoxyeicosatrienoic acids (EETs), synthesized from arachidonic acid by cytochrome P450 epoxygenases, are converted to dihydroxyeicosatrienoic acids by soluble epoxide hydrolase., Epoxyeicosatrienoic acids (EETs), which are synthesized from arachidonic acid by cytochrome P450 epoxygenases, function primarily as autocrine and paracrine effectors in the cardiovascular system and kidney., Epoxygenases metabolize arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EETs) and selected monohydroxyeicosatetraenoic acids (HETEs)., Epoxyeicosatrienoic acids (EETs) are potent lipid mediators formed by cytochrome P450 epoxygenases from arachidonic acid. , Epoxyeicosatrienoic acids (EETs) are bioactive eicosanoids produced from arachidonic acid by cytochrome P450 epoxygenases. , Epoxyeicosatrienoic acids (EETs), derived from arachidonic acid by cytochrome P450 epoxygenases, are potent vasodilators that function as endothelium-derived hyperpolarizing factors in some vascular beds. E, Epoxyeicosatrienoic acids (EETs), which are synthesized from arachidonic acid by cytochrome P450 epoxygenases, function primarily as autocrine and paracrine effectors in the cardiovascular system and kidney. T, poxyeicosatrienoic acids (EETs) are epoxy lipids derived from metabolism of arachidonic acid by cytochrome P450 epoxygenases. W, he vascular endothelium metabolizes arachidonic acid by cytochrome P450 epoxygenases to epoxyeicosatrienoic acids or EETs., Epoxyeicosatrienoic acids (EETs) are the epoxidation products of arachidonic acid catalyzed by cytochrome P450 (CYP) epoxygenases, which possess multiple biological activities. In , OBJECTIVE: Arachidonic acid metabolism by cytochrome P450 (CYP) epoxygenases leads to epoxyeicosatrienoic acids (EETs), which are eicosanoids with vasodilator and anti-inflammatory pro, Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play important and diverse roles in the cardiovascular system. Th, Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites produced by cytochrome P450 epoxygenases which are highly expressed in hepatocytes. , Epoxyeicosatrienoic acids (EETs) are epoxides of arachidonic acid generated by cytochrome P450 (CYP) epoxygenases., Although eicosanoids, including prostaglandins and leukotrienes, are best known as products of arachidonic acid metabolism by cyclooxygenases and lipoxygenases, arachidonic acid is also a substrate for another enzymatic pathway, the cytochrome P450 (CYP) system., Epoxyeicosatrienoic acids (EETs), lipid mediators synthesized from arachidonic acid by cytochrome P-450 epoxygenases, are converted by soluble epoxide hydrolase (SEH) to the corresponding dihydroxyeicosatrienoic acids (DHETs)., Epoxyeicosatrienoic acids (EETs) are synthesized from arachidonic acid by cytochrome P450 epoxygenases in endothelial cells., Epoxyeicosatrienoic acids (EETs), the eicosanoid biomediators synthesized from arachidonic acid by cytochrome P450 epoxygenases, are inactivated in many tissues by conversion to dihydroxyeicosatrienoic acids (DHETs)., Epoxyeicosatrienoic acids (EETs) are potent lipid mediators formed by cytochrome P450 epoxygenases from arachidonic acid., Recent studies show that mouse epidermis expresses CYP2B19, a keratinocyte-specific epoxygenase that generates 11,12- and 14,15-epoxyeicosatrienoic (EET) acids from arachidonate., Identification of rabbit cytochromes P450 2C1 and 2C2 as arachidonic acid epoxygenases., Epoxyeicosatrienoic acids (EETs) are formed from arachidonic acid by the action of P450 epoxygenases (CYP2C and CYP2J)., Epoxyeicosatrienoic acids (EETs) are generated from arachidonic acid by cytochrome P450 (CYP) epoxygenases.[SEP]Relations: Arachidonic Acid has relations: drug_drug with Aprepitant, drug_drug with Aprepitant, drug_drug with Phenylbutazone, drug_drug with Phenylbutazone, drug_drug with Apremilast, drug_drug with Apremilast, drug_drug with Ethinylestradiol, drug_drug with Ethinylestradiol. arachidonate 5-lipoxygenase activity has relations: molfunc_protein with ALOX5AP, molfunc_protein with ALOX5AP. Definitions: Arachidonic acid defined as following: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes.. EET defined as following: A class of eicosanoids produced by the epoxidation of one of the double bonds of arachidonic acid by some of the members of the cytochrome P450 family of epoxygenases. Epoxides in the epoxyeicosatrienoic acid (EET) family act locally to stimulate signaling pathways involved in the regulation of blood pressure, vascular maintenance, inflammation, and pain responses. EETs may promote the proliferation and survival of certain types of cancer cells.. arachidonate defined as following: polyunsaturated 20-carbon essential fatty acid found in animal fat or formed in biosynthesis from dietary linoleic acid; also, its salts, esters, or anions; precursor in the biosynthesis of leukotrienes, prostaglandins, and thromboxanes.. cyclooxygenases defined as following: An enzyme that converts arachidonic acid into biologically active prostanoids, such as prostaglandins, prostacyclins, and thromboxanes.. eicosanoids defined as following: A class of compounds named after and generally derived from C20 fatty acids (EICOSANOIC ACIDS) that includes PROSTAGLANDINS; LEUKOTRIENES; THROMBOXANES, and HYDROXYEICOSATETRAENOIC ACIDS. They have hormone-like effects mediated by specialized receptors (RECEPTORS, EICOSANOID).. hepatocytes defined as following: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.. myocardial defined as following: Of or pertaining to the myocardium.. vascular endothelium defined as following: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.. epoxide hydrolase defined as following: Enzymes that catalyze reversibly the formation of an epoxide or arene oxide from a glycol or aromatic diol, respectively.. Th defined as following: Tyrosine 3-monooxygenase (528 aa, ~59 kDa) is encoded by the human TH gene. This protein plays a role in the synthesis of dopamine from L-tyrosine.. endothelial defined as following: A layer of epithelium that lines the heart, blood vessels (ENDOTHELIUM, VASCULAR), lymph vessels (ENDOTHELIUM, LYMPHATIC), and the serous cavities of the body.. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. endothelial cells defined as following: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.. lipoxygenases defined as following: Dioxygenases that catalyze the peroxidation of methylene-interrupted UNSATURATED FATTY ACIDS.. arachidonic acid defined as following: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes..", "label": "yes"} {"id": "converted_2179", "sentence1": "Is airplane stroke syndrome a common disease.", "sentence2": "Only 37 cases of stroke during or soon after long-haul flights have been published to our knowledge. , Our centre admitted 5727 stroke patients, of whom 42 (0.73%) had flight-related strokes., The authors report three cases of ischemic stroke in young adults that occurred during or after an airplane flight.[SEP]Relations: Ischemic stroke has relations: disease_phenotype_positive with stroke disorder, disease_phenotype_positive with stroke disorder, disease_phenotype_positive with cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy,, disease_phenotype_positive with cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy,, disease_phenotype_positive with ZTTK syndrome, disease_phenotype_positive with ZTTK syndrome, disease_phenotype_positive with arterial tortuosity syndrome, disease_phenotype_positive with arterial tortuosity syndrome, disease_phenotype_positive with thoracic aortic aneurysm and aortic dissection, disease_phenotype_positive with thoracic aortic aneurysm and aortic dissection. Definitions: ischemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue.. stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810).", "label": "no"} {"id": "converted_1331", "sentence1": "Is there a difference in the rate between gene fusion and gene fission?", "sentence2": "we illustrate arrangement diversity within closely related organisms, estimate arrangement turnover frequency and establish, for the first time, branch-specific rate estimates for fusion, fission, domain addition and terminal loss., Rate and polarity of gene fusion and fission in Oryza sativa and Arabidopsis thaliana, We have identified all differentially composite or split genes in 2 fully sequenced plant genomes, Oryza sativa and Arabidopsis thaliana, Polarizing these events by outgroup comparison revealed differences in the rate of gene fission but not of gene fusion in the rice and Arabidopsis lineages. Gene fission occurred at a higher rate than gene fusion in the O. sativa lineage and was furthermore more common in rice than in Arabidopsis., Gene fusion and fission are thus rare and slow processes in higher plant genomes; they should be of utility to address deeper evolutionary relationships among plants--and the relationship of plants to other eukaryotic lineages--where sequence-based phylogenies provide equivocal or conflicting results., Primary factors correlating with fusion rates are the presence of transmembrane helices in HKs and the presence of DNA-binding domains in RRs, features that require correct (and separate) spatial location. In the absence of such features, there is a relative abundance of fused genes., We show that indels are the most frequent elementary events and that they occur in most cases at either the N- or C-terminus of the proteins. As revealed by the genomic neighbourhood/context of the corresponding genes, we show that a substantial number of these terminal indels are the consequence of gene fusions/fissions. We provide evidence showing that the contribution of gene fusion/fission to the evolution of multi-domain bacterial proteins is lower-bounded by 27% and upper-bounded by 64%. We conclude that gene fusion/fission is a major contributor to the evolution of multi-domain bacterial proteins., We found that fusion events are approximately four times more common than fission events, and we established that, in most cases, any particular fusion or fission event only occurred once during the course of evolution., Analyzing the most parsimonious pathways, we find 87% of architectures to gain complexity over time through simple changes, among which fusion events account for 5.6 times as many architectures as fission., These trees defined timelines of architectural discovery and revealed remarkable evolutionary patterns, including the explosive appearance of domain combinations during the rise of organismal lineages, the dominance of domain fusion processes throughout evolution, and the late appearance of a new class of multifunctional modules in Eukarya by fission of domain combinations, We searched for examples which have arisen by one of the three postulated mechanisms: independent fusion/fission, \"duplication/deletion,\" and plasmid-mediated \"cut and paste.\" We conclude that all three mechanisms can be observed, with the independent fusion/fission being the most frequent.[SEP]Relations: robinow syndrome, autosomal recessive 2 has relations: disease_phenotype_positive with Camptodactyly, disease_phenotype_positive with Camptodactyly, disease_phenotype_positive with Absent uvula, disease_phenotype_positive with Absent uvula, disease_phenotype_positive with Short stature, disease_phenotype_positive with Short stature, disease_phenotype_positive with Anteverted nares, disease_phenotype_positive with Anteverted nares, disease_phenotype_positive with Short nose, disease_phenotype_positive with Short nose. Definitions: gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. Oryza sativa defined as following: Annual cereal grass of the family POACEAE. Its starchy, EDIBLE GRAIN, rice, is the staple food of roughly one-half of the world's population.. bacterial proteins defined as following: Proteins found in any species of bacterium.. Eukarya defined as following: Organism or cells with a nucleus separated from the cytoplasm by a two membrance nuclear envelope and compartmentalization of function into distinct cytoplasmic organelles.. RRs defined as following: Autosomal recessive Robinow syndrome (RRS) is the less common type of Robinow syndrome (RS, see this term) characterized by short-limb dwarfism, costovertebral segmentation defects and abnormalities of the head, face and external genitalia.. plant genomes defined as following: The genetic complement of a plant (PLANTS) as represented in its DNA.. plants defined as following: Multicellular, eukaryotic life forms of kingdom Plantae. Plants acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations. It is a non-taxonomical term most often referring to LAND PLANTS. In broad sense it includes RHODOPHYTA and GLAUCOPHYTA along with VIRIDIPLANTAE.. organisms defined as following: A living entity..", "label": "yes"} {"id": "converted_895", "sentence1": "Does the histidine-rich Ca-binding protein (HRC) interact with triadin?", "sentence2": "The HRC effects on RyR may be regulated by the Ca(2+)-sensitivity of its interaction with triadin., In rabbit skeletal and cardiac muscles, HRC binds to sarcoplasmic reticulum (SR) membranes via triadin, a junctional SR protein. , HRC may play a key role in the regulation of SR Ca cycling through its direct interactions with SERCA2 and triadin, mediating a fine cross talk between SR Ca uptake and release in the heart., Histidine-rich calcium binding protein (HRC) is located in the lumen of sarcoplasmic reticulum (SR) that binds to both triadin (TRN) and SERCA affecting Ca(2+) cycling in the SR., HRC is a SR luminal Ca(2+) binding protein known to associate with both triadin and the sarcoplasmic reticulum Ca(2+)-ATPase, and may thus mediate the crosstalk between SR Ca(2+) uptake and release., The histidine-rich Ca(2+) binding protein (HRC) is a high capacity Ca(2+) binding protein in the sarcoplasmic reticulum (SR). Because HRC appears to interact directly with triadin, HRC may play a role in the regulation of Ca(2+) release during excitation-contraction coupling., In the present study, we have performed co-immunoprecipitation experiments and show that HRC binds directly to triadin, which is an integral membrane protein of the sarcoplasmic reticulum., A direct binding of HRC (histidine-rich Ca(2+)-binding protein) to triadin, the main transmembrane protein of the junctional sarcoplasmic reticulum (SR) of skeletal muscle, seems well supported., The present study documents the binding interaction of skeletal muscle sarcoplasmic reticulum (SR) transmembrane protein triadin with peripheral histidine-rich, Ca(2+)-binding protein (HCP)., In addition, the intra-luminal histidine-rich calcium binding protein (HRC) has been shown to interact with both SERCA2a and triadin., Notably, there is physical and direct interaction between these protein players, mediating a fine-cross talk between SR Ca-uptake, storage and release., The histidine-rich calcium-binding protein (HRCBP) is expressed in the junctional SR, the site of calcium release from the SR. HRCBP is expressed exclusively in muscle tissues and binds calcium with low affinity and high capacity. In addition, HRCBP interacts with triadin, a protein associated with the ryanodine receptor and thought to be involved in calcium release. Its calcium binding properties, localization to the SR, and interaction with triadin suggest that HRCBP is involved in calcium handling by the SR., Using a fusion protein binding assay, we further identified the histidine-rich acidic repeats of HRC as responsible for the binding of HRC to triadin. , The HRC binding domain of triadin was also localized by fusion protein binding assay to the lumenal region containing the KEKE motif that was previously shown to be involved in the binding of triadin to calsequestrin. Notably, the interaction of HRC and triadin is Ca(2+)-sensitive. Our data suggest that HRC may play a role in the regulation of Ca(2+) release from the sarcoplasmic reticulum by interaction with triadin., Further support for colocalization of HRC with triadin cytoplasmic domain is provided here by experiments of mild tryptic digestion of tightly sealed TC vesicles., We demonstrate that HRC can be isolated as a complex with triadin, following equilibrium sucrose-density centrifugation in the presence of mM Ca(2+)., Here, we characterized the COOH-terminal portion of rabbit HRC, expressed and purified as a fusion protein (HRC(569-852)), with respect to Ca(2+)-binding properties, and to the interaction with triadin on blots, as a function of the concentration of Ca(2+)., Our results identify the polyglutamic stretch near the COOH terminus, as the Ca(2+)-binding site responsible, both for the acceleration in mobility of HRC on SDS-PAGE in the presence of millimolar concentrations of Ca(2+), and for the enhancement by high Ca(2+) of the interaction between HRC and triadin cytoplasmic segment., In addition to providing further evidence that HCP coenriches with RyR1, FKBP-12, triadin and calsequestrin (CS) in sucrose-density-purified TC vesicles, using specific polyclonal antibody, we show it to be expressed as a single protein species, both in fast-twitch and slow-twitch fibers, and to identically localize to the I-band., Colocalization of HCP and triadin at junctional triads is supported by the overlapping staining pattern using monoclonal antibodies to triadin. We show a specific binding interaction between digoxigenin-HCP and triadin, using ligand blot techniques., Suggesting that triadin dually interacts with HCP and with CS, at distinct sites, we have found that triadin-CS interaction in overlays does not require the presence of Ca2+., These differential effects form the basis for the hypothesis that HCP anchors to the junctional membrane domain of the SR, through binding to triadin short cytoplasmic domain at the NH2 terminus., Although the function of this interaction, as such, is not well understood, it seems of potential biological interest within the more general context of the structural-functional role of triadin at the triadic junction in skeletal muscle., BACKGROUND: Histidine-rich calcium binding protein (HRC) is located in the lumen of sarcoplasmic reticulum (SR) that binds to both triadin (TRN) and SERCA affecting Ca(2+) cycling in the SR. Chronic overexpression of HRC that may disrupt intracellular Ca(2+) homeostasis is implicated in pathogenesis of cardiac hypertrophy., Interaction of HRC (histidine-rich Ca(2+)-binding protein) and triadin in the lumen of sarcoplasmic reticulum., The histidine-rich Ca-binding protein (HRC) is an SR component that binds to triadin and may affect Ca release through the ryanodine receptor., The histidine-rich Ca-binding protein (HRC) is an SR component that binds to triadin and may affect Ca release through the ryanodine receptor, Because HRC appears to interact directly with triadin, HRC may play a role in the regulation of Ca(2+) release during excitation-contraction coupling, A direct binding of HRC (histidine-rich Ca(2+)-binding protein) to triadin, the main transmembrane protein of the junctional sarcoplasmic reticulum (SR) of skeletal muscle, seems well supported, The histidine-rich Ca-binding protein (HRC) is an SR component that binds to triadin and may affect Ca release through the ryanodine receptor[SEP]Relations: protein binding has relations: molfunc_protein with HRC, molfunc_protein with HRC, molfunc_protein with HRK, molfunc_protein with HRK, molfunc_protein with HRAS, molfunc_protein with HRAS, molfunc_protein with HRG, molfunc_protein with HRG, molfunc_protein with CA3, molfunc_protein with CA3. Definitions: calcium defined as following: A dietary supplement containing the mineral calcium.. RyR defined as following: A voltage-gated calcium-release channel complex of the sarcoplasmic or endoplasmic reticulum. It plays an important role in the excitation-contraction (E-C) coupling of muscle cells. RyR comprises a family of ryanodine receptors, widely expressed throughout the animal kingdom. [GOC:ame, PMID:22822064]. cytoplasmic domain defined as following: The part of a transmembrane protein which projects into the cytoplasm.. SR defined as following: Human SNCG wild-type allele is located within10q23.2-q23.3 and is approximately 13 kb in length. This allele, which encodes gamma-synuclein protein, plays a role in the modulation of axonal architecture and neurofilament integrity. This gene is highly expessed in advanced breast carcinomas, suggesting a correlation between SNCG overexpression and breast tumor development.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. FKBP-12 defined as following: A 12-KDa tacrolimus binding protein that is found associated with and may modulate the function of calcium release channels. It is a peptidyl-prolyl cis/trans isomerase which is inhibited by both tacrolimus (commonly called FK506) and SIROLIMUS.. transmembrane protein defined as following: A protein that is an integral membrane protein with a transmembrane region.. lumen defined as following: A SI derived unit of luminous flux. It is the amount of light that falls on a unit area at unit distance from a source of one candela.. sarcoplasmic reticulum defined as following: A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. monoclonal antibodies defined as following: Antibodies produced by a single clone of cells.. fusion protein defined as following: Tumor suppressor candidate 2 (110 aa, ~12 kDa) is encoded by the human TUSC2 gene. This protein is involved in cell cycle regulation and tumor suppression.. muscle tissues defined as following: Contractile tissue that produces movement in animals.. sarcoplasmic reticulum Ca(2+)-ATPase defined as following: Calcium-transporting ATPases that catalyze the active transport of CALCIUM into the SARCOPLASMIC RETICULUM vesicles from the CYTOPLASM. They are primarily found in MUSCLE CELLS and play a role in the relaxation of MUSCLES.. cardiac hypertrophy defined as following: Enlargement of the HEART due to chamber HYPERTROPHY, an increase in wall thickness without an increase in the number of cells (MYOCYTES, CARDIAC). It is the result of increase in myocyte size, mitochondrial and myofibrillar mass, as well as changes in extracellular matrix.. cardiac muscles defined as following: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.. integral membrane protein defined as following: The component of the endoplasmic reticulum membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane. [GOC:dos, GOC:mah]. ryanodine receptor defined as following: A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES..", "label": "yes"} {"id": "converted_275", "sentence1": "Is shotgun lipidomics the direct infusion of a lipid sample into a mass spectrometer?", "sentence2": "In direct infusion/injection (or shotgun) lipidomics, An efficient shotgun lipidomics strategy was established and optimized for fast phospholipid profiling of viscera from three fish species: Lateolabrax japonicas, Ctenopharyngodon idellus, and Carassius auratus. This strategy relies on direct infusion of total lipid extracts into a tandem mass spectrometer without additional separation of the individual molecular species. , Top-down shotgun lipidomics relies on direct infusion of total lipid extracts into a high-resolution tandem mass spectrometer, shotgun lipidomic approaches that use direct infusion, direct infusion (shotgun lipidomics) , direct infusion-based shotgun lipidomics approaches, shotgun lipidomics (MDMS-SL) data, which are acquired directly from lipid extracts after direct infusion , Through direct infusion of the resultant enriched solution, we identified and quantitated a variety of very-low-abundance sphingolipid classes (e.g., sphingosine, psychosine, and lysosphingomyelin) and molecular species (e.g., sphingomyelin) using electrospray ionization mass spectrometry (i.e., shotgun sphingolipidomics).[SEP]Relations: phosphatidylcholine biosynthesis from sn-glycero-3-phosphocholine has relations: bioprocess_bioprocess with phosphatidylcholine biosynthetic process, bioprocess_bioprocess with phosphatidylcholine biosynthetic process. Sphingosine has relations: drug_protein with PVR, drug_protein with PVR, drug_protein with GLTP, drug_protein with GLTP, drug_protein with ABCB1, drug_protein with ABCB1. Definitions: viscera defined as following: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen.. sphingosine defined as following: An amino alcohol with a long unsaturated hydrocarbon chain. Sphingosine and its derivative sphinganine are the major bases of the sphingolipids in mammals. (Dorland, 28th ed). psychosine defined as following: An intermediate in the biosynthesis of cerebrosides. It is formed by reaction of sphingosine with UDP-galactose and then itself reacts with fatty acid-Coenzyme A to form the cerebroside.. sphingomyelin defined as following: A class of sphingolipids found largely in the brain and other nervous tissue. They contain phosphocholine or phosphoethanolamine as their polar head group so therefore are the only sphingolipids classified as PHOSPHOLIPIDS..", "label": "yes"} {"id": "converted_362", "sentence1": "Is there a package in R/bioconductor for classification of alternative splicing?", "sentence2": "spliceR: an R package for classification of alternative splicing and prediction of coding potential from RNA-seq data., Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential., spliceR uses the full-length transcript output from RNA-seq assemblers to detect single or multiple exon skipping, alternative donor and acceptor sites, intron retention, alternative first or last exon usage, and mutually exclusive exon events. For each of these events spliceR also annotates the genomic coordinates of the differentially spliced elements, facilitating downstream sequence analysis. For each transcript isoform fraction values are calculated to identify transcript switching between conditions. Lastly, spliceR predicts the coding potential, as well as the potential nonsense mediated decay (NMD) sensitivity of each transcript., Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential., Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential. , Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential.[SEP]Relations: rRNA transcription has relations: bioprocess_bioprocess with 5S class rRNA transcription by RNA polymerase III, bioprocess_bioprocess with 5S class rRNA transcription by RNA polymerase III, bioprocess_protein with SIRT7, bioprocess_protein with SIRT7, bioprocess_protein with NPM3, bioprocess_protein with NPM3, bioprocess_protein with ANG, bioprocess_protein with ANG, bioprocess_protein with TP53, bioprocess_protein with TP53. Definitions: spliceR defined as following: A device designed to join pieces of a material into a continuous length.. transcript defined as following: The initial RNA molecule produced by transcription.. RNA-seq defined as following: A procedure that can determine the nucleotide sequence for all of the RNA transcripts in an individual.. alternative splicing defined as following: A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different..", "label": "yes"} {"id": "converted_147", "sentence1": "Has the protein TIEG1 been associated with apoptosis?", "sentence2": "TGF-beta) inducible early gene 1 (TIEG1) is known to induce apoptosis in TGF-beta sensitive pancreatic cancer cells, yet its effect on TGF-beta resistant cancer cells remains unclear, overexpression of TIEG1, protected ALL cells against chemotherapy-induced cell death, TIEG1 might be involved in mediating this effect from the microenvironment onto the leukemia cells, We also demonstrate that TIEG-1 ectopic expression in CGNPs induces cell cycle arrest that can lead to apoptosis but fails to promote differentiation, TIEG1 acts as an inducer or repressor of gene transcription to enhance the TGFbeta/Smad pathway, as well at other signaling pathways, to regulate cell proliferation, differentiation, and apoptosis., TGFbeta inducible early gene (TIEG1) mimics TGFbeta action and induces apoptosis, the transforming growth factor-beta- (TGF-beta-) inducible early response 1 gene (TIEG1), which plays a pivotal role in TGF-beta-regulated cell growth control and apoptosis, Induction of mRNA for Smad4 and the TGF-beta1-regulated apoptosis-inducing transcription factor TGF-beta1-inducible early gene (TIEG1) was detected within the first 6 h of doxazosin treatmen, TIEG1 (TGF-beta inducible early gene) is a recently characterized transcription factor regulated by TGF-beta that induces apoptosis when overexpressed in pancreatic adenocarcinoma cell lines, Influence of TIEG1 on apoptosis, the influence of TIEG1 on apoptosis of HL-60 cells and the expression of Bcl-2/Bax, The expression of genes involved in insulin resistance (PDK4, AHSG) is increased, together with expression of TIEG1, a transcription factor that can induce apoptosis via the mitochondrial pathway, the overexpression of TIEG1 mediated growth inhibition and apoptosis in TGF-β1-resistant HCC cell lines,, On the other hand, KLF10 deficient keratinocytes showed increased proliferation and apoptosis, LF10, transforming growth factor-β-inducible early gene 1, IEG1 can induce apoptosis of cancer cells, TGF-β inducible early gene 1) plays a significant role in regulating cell proliferation and apoptosis, TIEG1) is a Krüppel-like transcription factor (KLF10) that was originally cloned from human osteoblasts as an early response gene to TGF-β treatment, Adenoviral delivery of TIEG1 (AdTIEG1) to TIEG1(-/-) cells reversed the RANKL-induced NFATc1 signaling defect in TIEG1(-/-) precursors and eliminated the differentiation and apoptosis defects, (TGF)-β inducible early gene (TIEG)-1 is implicated in the control of cell proliferation, differentiation, and apoptosis in some cell types, TIEG1 has been shown to mimic the effects of TGF-beta in various carcinoma cells and plays a critical role in the apoptotic cascade, (TIEG) is a family of primary response genes induced by TGF-beta, which are well recognized in regulating cellular proliferation and apoptosis, In human and murine tissues it has been shown that TIEG1 and TIEG2 induce apoptosis and inhibit cell growth, overexpression of TIEG1 in OLI-neu cells induced apoptosis, (TGF-beta(1))-inducible transcription factors have recently elicited interest because of their critical role in the regulation of cell proliferation, differentiation, and apoptosis, ectopic overexpression of TIEG is sufficient to trigger the apoptotic cell program in these cells[SEP]Relations: transcription factor binding has relations: molfunc_protein with DRG1, molfunc_protein with DRG1, molfunc_protein with ATG7, molfunc_protein with ATG7, molfunc_protein with APBB1, molfunc_protein with APBB1, molfunc_protein with TLE1, molfunc_protein with TLE1, molfunc_protein with KEAP1, molfunc_protein with KEAP1. Definitions: keratinocytes defined as following: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.. HL-60 cells defined as following: A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8). leukemia defined as following: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006). pancreatic adenocarcinoma defined as following: An adenocarcinoma which arises from the exocrine pancreas. Ductal adenocarcinoma and its variants are the most common types of pancreatic adenocarcinoma.. PDK4 defined as following: [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial (411 aa, ~46 kDa) is encoded by the human PDK4 gene. This protein plays a role in the inhibition of pyruvate dehydrogenase activity.. TGF-beta defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine transforming growth factor-beta (TGF-beta) with proapoptotic and antineoplastic properties. TGF-beta may suppress tumor cell growth by decreasing the expression of cyclin D1, a cell cycle regulatory protein, and downregulating the expression of the oncogene c-myc. This agent is also involved in T cell-mediated immunosuppression by CD4+CD25+ T cells, which permits cancer cells to evade immune surveillance. (NCI04). mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.. cancer cells defined as following: Cells of, or derived from, a malignant tumor.. transcription factor defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. Smad4 defined as following: Mothers against decapentaplegic homolog 4 (552 aa, ~60 kDa) is encoded by the human SMAD4 gene. This protein is involved in cytokine signaling and transcription factor activity.. murine defined as following: Any of numerous species of small rodents belonging to the genus Mus and various related genera of the family Muridae.. early response 1 gene defined as following: Human ERG wild-type allele is located in the vicinity of 21q22.3 and is approximately 280 kb in length. This allele, which encodes transcriptional regulator ERG protein, is involved in both the regulation of RNA polymerase II-directed transcription and the modification of local chromatin structure. Acute myelogenous leukemia of the subtype M2 is linked to the chromosomal translocation t(8;21)(q22;q22), which involves this gene and the EWSR1 gene. Human myeloid leukemia is linked to the chromosomal translocation t(16;21)(p11;q22) of this gene with the FUS gene.. pancreatic cancer defined as following: A primary or metastatic malignant tumor involving the pancreas. Representative examples include carcinoma and lymphoma.. ALL defined as following: Leukemia with an acute onset, characterized by the presence of lymphoblasts in the bone marrow and the peripheral blood. It includes the acute B lymphoblastic leukemia and acute T lymphoblastic leukemia.. human defined as following: Members of the species Homo sapiens.. AHSG defined as following: This gene is involved in bone mineralization.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species..", "label": "yes"} {"id": "converted_697", "sentence1": "Are there randomised controlled trials on sevoflurane?", "sentence2": "After Ethics Review Board approval, 44 ASA I-III patients undergoing elective gynaecological surgery were randomised after surgery to either hypercapnic hyperpnoea or control groups., Hypercapnic hyperpnoea in spontaneously breathing patients halves the time of recovery from sevoflurane-induced anaesthesia in the operating room., A total of 200 women undergoing first trimester abortion (American Society of Anesthesiologists physical status I) participated in the study. Patients were randomly assigned to receive either sevoflurane or propofol for short-term sedation., The results showed the incidence of dreaming was significantly different between anaesthesia groups with 60% (60/100) of the sevoflurane group and 33% (33/100) of the propofol group (P=0.000), Anaesthesia administered had no effect on patient satisfaction. The results suggest that the incidence of dreaming was not affected by recovery time. Patient satisfaction was not influenced by choice of sedative and/or by the occurrence of dreaming during sevoflurane or propofol short-term sedation., Prior reports suggest that dreaming during anaesthesia is dependent on recovery time. Dreaming during sedation may impact patient satisfaction, Sevoflurane vs. propofol in patients with coronary disease undergoing mitral surgery: a randomised study., We therefore performed a randomised controlled trial (sevoflurane vs. propofol) to compare cardiac troponin release in patients with coronary disease undergoing mitral surgery., Myocardial injury in remifentanil-based anaesthesia for off-pump coronary artery bypass surgery: an equipotent dose of sevoflurane versus propofol, This randomised controlled trial compared the effect of equipotent anaesthetic doses of sevoflurane (S group) versus propofol (P group), during remifentanil-based anaesthesia for off-pump coronary artery bypass surgery, on myocardial injury. Either sevoflurane or propofol was titrated to maintain bispectral index values between 40 and 50., This randomised, multicentre, parallel-group trial included 98 adult patients. Patients received intravenous propofol for induction followed by sevoflurane maintenance anaesthesia., Patients were randomly allocated to receive sugammadex 2.0 mg kg(-1) or neostigmine 50 microg, We compared the haemodynamics, emergence and recovery characteristics of total intravenous anaesthesia using propofol/remifentanil with sevoflurane/remifentanil anaesthesia, under bispectral index guidance, in 103 patients undergoing surgical procedures lasting > 3.5 h, A randomised controlled trial of paediatric conscious sedation for dental treatment using intravenous midazolam combined with inhaled nitrous oxide or nitrous oxide/sevoflurane, Intravenous midazolam, especially in combination with inhaled nitrous oxide or sevoflurane and nitrous oxide, are effective techniques, with the combination of midazolam and sevoflurane the one most likely to result in successful treatment., We randomly assigned 1063 adult and 322 paediatric elective patients to one of four (adult) or two (paediatric) anaesthesia groups, In both studies, there was no difference in postdischarge outcomes at Day 7. Sevoflurane/sevoflurane was more costly with higher PONV rates in both studies. In adults, the cost per extra episode of PONV avoided was pound 296 (propofol/propofol vs. propofol/ sevoflurane) and pound 333 (propofol/sevoflurane vs. propofol/isoflurane)., Comparison of sevoflurane and nitrous oxide mixture with nitrous oxide alone for inhalation conscious sedation in children having dental treatment: a randomised controlled trial., We studied 411 children aged 3-10 years who were referred for dental treatment. They were randomly allocated to have inhalation conscious sedation with either sevoflurane/nitrous oxide mixture or nitrous oxide alone[SEP]Relations: Sevoflurane has relations: drug_drug with Enflurane, drug_drug with Enflurane, drug_drug with Propanidid, drug_drug with Propanidid, drug_drug with Ancrod, drug_drug with Ancrod, drug_drug with Selegiline, drug_drug with Selegiline, drug_drug with Cannabidiol, drug_drug with Cannabidiol. Definitions: sevoflurane defined as following: A fluorinated isopropyl ether with general anesthetic property. Although the mechanism of action has not been fully elucidated, sevoflurane may act by interfering with the release and re-uptake of neurotransmitters at post-synaptic terminals, and/or alter ionic conductance following receptor activation by a neurotransmitter. Sevoflurane may also interact directly with lipid matrix of neuronal membranes, thereby affecting gating properties of ion channels. In addition, this agent may activate gamma-aminobutyric acid (GABA) receptors hyperpolarizing cell membranes. This results in a general anesthetic effect, a decrease in myocardial contractility and mean arterial pressure as well as an increased respiratory rate.. PONV defined as following: Emesis and queasiness occurring after anesthesia.. nitrous oxide defined as following: Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. It is also used as a food aerosol in the preparation of whipping cream.. propofol defined as following: An intravenous anesthetic agent which has the advantage of a very rapid onset after infusion or bolus injection plus a very short recovery period of a couple of minutes. (From Smith and Reynard, Textbook of Pharmacology, 1992, 1st ed, p206). Propofol has been used as ANTICONVULSANTS and ANTIEMETICS.. midazolam defined as following: A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.. neostigmine defined as following: A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike PHYSOSTIGMINE, does not cross the blood-brain barrier.. coronary disease defined as following: Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause..", "label": "yes"} {"id": "converted_1526", "sentence1": "Is there an association between presenteeism and depression?", "sentence2": "Presenteeism was positively associated with severity of depression (Health and Work Performance Questionnaire, P < 0.0001; WPAI, P < 0.0001)., Statistically significant correlations (0.32-0.53) were found between presenteeism and increasing disability, fatigue, depression, anxiety, and reduced quality of life. , Presenteeism was associated with increasing fatigue, depression, anxiety, and reduced quality of life., Factors with less contribution to presenteeism included physical limitations, depression or anxiety, inadequate job training, and problems with supervisors and coworkers. , BACKGROUND: Subthreshold depression is highly prevalent in the general population and causes great loss to society especially in the form of reduced productivity while at work (presenteeism)., Two major causes of worker presenteeism (reduced on-the-job productivity as a result of health problems) are musculoskeletal pain and mental health issues, particularly depression. , Pain and depression were significantly associated with presenteeism. Pr, Survey adjusted multivariable logistic regression assessed classification of 12-month, depression-related presenteeism on the basis of socio-demographic, financial, work and health factors. , RESULTS: The LPT from absenteeism and presenteeism (reduced performance while present at work) was significantly higher among the MDD group., BACKGROUND: Depression is reported to be a major cause of illness-related sub-optimal work performance (presenteeism). , BACKGROUND: It is amply documented that mood disorders adversely affect job satisfaction, workforce productivity, and absenteeism/presenteeism. , The difference in productivity loss due to impaired presenteeism was significantly different between the two groups, but the productivity loss due to absenteeism was not. , Disease activity (OR 3.24, 95% CI 1.11-9.48) and depression (OR 3.22, 95% CI 1.22-8.48) were associated with absenteeism, while depression (OR 5.69, 95% CI 1.77-18.27, disease activity (OR 3.97, 95% CI 1.76-8.98), anxiety (OR 3.90, 95% CI 1.83-8.31), self-efficacy (OR 0.71, 95% CI 0.58-0.86), and increasing age (OR 1.04 per year, 95% CI 1.00-1.08) were associated with presenteeism. , Depression, in particular, appears to be associated with employment, absenteeism, and presenteeism, and should therefore be prioritized in clinical practice., Depression frequently causes unemployment, absenteeism, and presenteeism, which results in significantly reduced productivity., Presenteeism and absenteeism were significantly worse for the depression group at each time point (p < or = .001). In cross-sectional models, presenteeism was associated with more severe depression symptoms, poorer general physical health, psychologically demanding work, the interaction ofpsychologically demanding work with depression, and less job control (r2 range = .33-.54)., Chronic conditions such as depression/anxiety, obesity, arthritis, and back/neck pain are especially important causes of productivity loss. Comorbidities have significant non-additive effects on both absenteeism and presenteeism., RESULTS: At baseline, all presenteeism measures were sensitive to differences between those with (N=69) and without (N=363) depression/anxiety., Depression and anxiety were more consistently associated with \"presenteeism\" (that is, lost productivity while at work) than with absenteeism, whether this was measured by cutback days or by direct questionnaires., RESULTS: Substantial research exists about anxiety and depression costs, such as performance and productivity, absenteeism, presenteeism, disability, physical disability exacerbation, mental health treatment, increased medical care costs, exacerbating of physical illness, and studies of mental health care limitations and cost-offset., The author discusses the etiology and potential solutions for managing this new component in the productivity equation and in addressing depression, the major contributor to presenteeism., For employees who are currently depressed, recent research evidence has demonstrated that pharmacotherapy can have a dramatic and positive effect on lost productivity, absenteeism, and presenteeism., Among participants who were still employed, those with depression had significantly more job turnover, presenteeism, and absenteeism. , Only depression affected both absenteeism-presenteeism and critical incidents. , CONCLUSIONS: Depressive disorders in the workplace persist over time and have a major effect on work performance, most notably on \"presenteeism,\" or reduced effectiveness in the workplace. , The negative effects of depression include those on patients' occupational functioning, including absenteeism, presenteeism, and reduced opportunities for educational and work success. , The remitted group demonstrated a significant improvement in productivity (particularly presenteeism) when compared with the new visit group (Z = -3.29, p = 0.001)., Depression in workers leads to significant absenteeism, \"presenteeism\" (diminished capacity due to illness while still present at work), and significantly increased medical expenses in addition to the costs of psychiatric care. , Significant predictors of presenteeism and activity impairment at follow-up (controlled for gender, age, spondyloarthritis subgroups and presenteeism at baseline) were presenteeism at baseline, poor quality of life, worse disease activity, decreased physical function, lower self-efficacy pain and symptom, higher scores of anxiety, depression, smoking and low education level, and for activity impairment also female sex. , \" Pain and depression were significantly associated with presenteeism., Only depression affected both absenteeism-presenteeism and critical incidents., Factors with less contribution to presenteeism included physical limitations, depression or anxiety, inadequate job training, and problems with supervisors and coworkers.[SEP]Relations: anxiety disorder has relations: disease_disease with postpartum depression, disease_disease with postpartum depression, disease_disease with neurotic depression, disease_disease with neurotic depression, disease_disease with unipolar depression, disease_disease with unipolar depression. major depressive disorder has relations: disease_disease with endogenous depression, disease_disease with endogenous depression, disease_disease with endogenous depression, disease_disease with endogenous depression. Definitions: arthritis defined as following: Acute or chronic inflammation of JOINTS.. MDD defined as following: Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5). musculoskeletal pain defined as following: Discomfort stemming from muscles, LIGAMENTS, tendons, and bones.. Depressive disorders defined as following: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent.. depressed defined as following: An emotional state characterized by feelings of sadness, emptiness, and/or tearfulness.. anxiety defined as following: Persistent and disabling ANXIETY.. fatigue defined as following: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.. illness defined as following: A state of ill health, bodily malfunction, or discomfort.. presenteeism defined as following: Reporting for work despite feeling ill.. mood disorders defined as following: Those disorders that have a disturbance in mood as their predominant feature..", "label": "yes"} {"id": "converted_3360", "sentence1": "Does SATB1 regulate the RAG1 and RAG2 genes?", "sentence2": "High level expression of the Xlr nuclear protein in immature thymocytes and colocalization with the matrix-associated region-binding SATB1 protein, Its onset preceded the rearrangement of TCR genes, as Xlr expression was conserved in thymus cells from RAG1(0/0) mice. , An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development., SATB1 binds to the ASE and Rag promoters, facilitating inclusion of Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters., Our results provide a novel framework for understanding ASE function and demonstrate a novel role for SATB1 as a regulator of Rag locus organization and gene expression in DP thymocytes.[SEP]Relations: Tat protein binding has relations: molfunc_protein with DNAJA1, molfunc_protein with DNAJA1, molfunc_protein with GABARAPL1, molfunc_protein with GABARAPL1, molfunc_protein with CTDP1, molfunc_protein with CTDP1. transcription-coupled nucleotide-excision repair has relations: bioprocess_protein with DDB1, bioprocess_protein with DDB1, bioprocess_protein with XAB2, bioprocess_protein with XAB2. Definitions: RNA polymerase II defined as following: A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC 2.7.7.6.. Rag2 defined as following: This gene plays a role in immunoglobulin diversity.. thymocyte defined as following: HEMATOPOIETIC PROGENITOR CELLS that have migrated to the THYMUS where they differentiate into T-LYMPHOCYTES. Thymocytes are classified into maturational stages based on the expression of CELL SURFACE ANTIGENS.. SATB1 defined as following: DNA-Binding Protein SATB1 (763 aa, ~86 kDa) is encoded by the human SATB1 gene. This protein binds DNA and may be involved in the regulation of transcription.. TCR defined as following: The nucleotide-excision repair process that carries out preferential repair of DNA lesions on the actively transcribed strand of the DNA duplex. In addition, the transcription-coupled nucleotide-excision repair pathway is required for the recognition and repair of a small subset of lesions that are not recognized by the global genome nucleotide excision repair pathway. [PMID:10197977, PMID:11900249]. Rag1 defined as following: Genes involved in activating the enzyme VDJ recombinase. RAG-1 is located on chromosome 11 in humans (chromosome 2 in mice) and is expressed exclusively in maturing lymphocytes..", "label": "yes"} {"id": "converted_897", "sentence1": "Does magnesium sulfate improve outcomes of subarachnoid hemorrhage patients?", "sentence2": "CONCLUSION: Patients assigned a higher serum magnesium concentration had a reduced incidence of vasospasm as seen by angiography, but the difference was not statistically significant. Clinically significant outcomes were not different between groups., 158 patients (26·2%) had poor outcome in the magnesium group compared with 151 (25·3%) in the placebo group (risk ratio [RR] 1·03, 95% CI 0·85-1·25). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0·96, 95% CI 0·86-1·08). INTERPRETATION: Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended. , There is a tendency in the magnesium group to have better outcomes. , Due to inconsistently reported benefits and the occurrence of side effects, phase II data suggested that intravenous magnesium for SAH provided either no overall net benefit or uncertain trade-offs. Benefit was likewise not supported in the single phase III clinical trial., tatistically significant clinical benefits could not be demonstrated for the other drugs (clazosentan, statins, and magnesium). CONCLUSIONS: Insufficient evidence is available to support the use of the triple-H therapy, clazosentan, statins, or magnesium sulfate for the prevention of cerebral vasospasm following subarachnoid hemorrhage. , Magnesium sulfate decreased the rate of cerebral infarction, but not of DCI or poor functional outcome. Regarding outcome, a beneficial effect of magnesium sulfate on outcome can not be ruled out because of sample size limitations., CONCLUSIONS: The present findings do not lend support to a beneficial effect of magnesium sulphate infusion on delayed cerebral infarction. The reduction in DCI and improvement in the clinical outcomes of aneurysmal SAH patients following magnesium sulphate infusion observed in previous pilot studies are not confirmed, although a beneficial effect cannot be ruled out because of sample size limitation., Favorable outcome (Good recovery and moderate disability, as defined by Glasgow Outcome Scale) was achieved in 20 of 30 (67%) patients receiving magnesium sulfate infusion and 16 of 30 (53%) patients receiving placebo treatment, p = 0.292, odds ratio 1.750, 95% CI 0.616-4.974., Similarly, the pooled odds ratio for favorable outcome is 1.598, 95% CI 1.074-2.377, statistically significant. , RESULTS: The worst clinical outcomes at 6 months were seen in MgSO(4) group patients, with mean plasma magnesium concentrations in the fourth quartile, and in placebo group patients, with mean such concentrations in the third and fourth quartiles. CONCLUSIONS: No evidence was found to suggest that a higher mean plasma magnesium concentration improves clinical outcomes. On the contrary, we found an association between high plasma magnesium concentration and worse clinical outcomes., The proportions of patients with a favorable outcome at 6 months (Extended Glasgow Outcome Scale 5 to 8) were similar, 64% in the magnesium sulfate group and 63% in the saline group (OR, 1.0; 95% CI, 0.7 to 1.6). Secondary outcome analyses (modified Rankin Scale, Barthel Index, Short Form 36, and clinical vasospasm) also showed no significant differences between the 2 groups. , CONCLUSIONS: The results do not support a clinical benefit of intravenous magnesium sulfate infusion over placebo infusion in patients with acute aneurysmal subarachnoid hemorrhage., Magnesium infusion reduced the risk of poor outcome and delayed cerebral ischemia (DCI): the relative risk was 0.62 (95% confidence interval (CI) 0.46-0.83) and 0.73 (95% CI 0.53-1.00), respectively. , CONCLUSION: The meta-analysis suggests that intravenous magnesium therapy reduces the risk of DCI and poor outcome after aneurysmal SAH. , The incidence of delayed ischemic infarction was significantly lower in magnesium-treated patients (22% vs. 51%; p = .002); 34 of 54 magnesium patients and 27 of 53 control patients reached good outcome (p = .209)., BACKGROUND: A meta-analysis of current data suggests that magnesium sulfate infusion improves the outcome after aneurysmal subarachnoid hemorrhage through a reduction in delayed ischemic neurological deficit. , These data imply that intravenous magnesium therapy, besides a supposed beneficial effect on outcome, also provides pain relief for SAH patients, for whom it might also improve functional outcome., Preliminary evidence has suggested that magnesium sulfate infusion reduces delayed ischemic neurological deficit and improves clinical outcome after aneurysmal subarachnoid hemorrhage. , In a phase II randomized clinical trial of 283 patients, magnesium treatment reduced the risk of DCI by 34% and of poor outcome by 23%., BACKGROUND: Recent studies suggest that high-dose MgSO4 therapy is safe and reduces the incidence of DIND and subsequent poor outcome after SAH. , On-treatment analysis showed a significantly better outcome after 3 months (P = .017) and a trend toward better outcome after 1 year (P = .083). , CONCLUSIONS: High-dose MgSO4 therapy might be efficient as a prophylactic adjacent therapy after SAH to reduce the risk for poor outcome. , There was no significant difference in mortality rate at discharge (p = 0.328). A trend toward improved outcome as measured by the modifed Rankin Scale (p = 0.084), but not the Glasgow Outcome Scale (p = 1.0), was seen in the MgSO4 treated group. CONCLUSIONS: Analysis of the results suggests that MgSO4 infusion may have a role in cerebral vasospasm prophylaxis if therapy is initiated within 48 hours of aneurysm rupture., There was, however, no difference between groups in functional recovery or Glasgow Outcome Scale score. , Patients receiving MgSO4 tended to have fewer neurological deficits, better functional recovery and an improved score in GOS. , CONCLUSIONS: MgSO4 infusion after aneurysmal SAH is well tolerated and may be useful in producing better outcome., CONCLUSION: Magnesium did not seem to interfere in vasospasm frequency but apparently acted favorably in decreasing morbidity and length of hospital stay., None of the patients died; no CT evidence of ischemic infarction was present; and most had good outcomes (GOS 5 in 10 patients; GOS 4 in 8 patients)., At that time, 18 patients in the treatment group and 6 in the placebo group had an excellent outcome (risk ratio, 3.4; 95% CI, 1.3 to 8.9). CONCLUSIONS: This study suggests that magnesium reduces DCI and subsequent poor outcome, but the results are not yet definitive. , We observed a trend in which a higher percentage of patients obtained GOS scores of 4 or 5 in the group treated with MgSO4, but the trend did not reach a statistically significant level. , Magnesium sulfate treatment improves outcome in patients with subarachnoid hemorrhage: a meta-analysis study., BACKGROUND AND PURPOSE: Pilot clinical trials using magnesium sulfate in patients with acute aneurysmal subarachnoid hemorrhage have reported trends toward improvement in clinical outcomes., Preliminary evidence has suggested that magnesium sulfate infusion reduces delayed ischemic neurological deficit and improves clinical outcome after aneurysmal subarachnoid hemorrhage., Our results indicate that although there was reduced likelihood of a poor outcome for patients treated with magnesium sulfate after SAH, patient mortality was not improved., CONCLUSION: Administration of intra-arterial magnesium sulfate in combination with nicardipine was well tolerated in patients with subarachnoid hemorrhage and cerebral vasospasm without a significant change in MAP and ICP., Current evidence does not support the prophylactic use of magnesium sulfate in aneurysmal subarachnoid hemorrhage, Preliminary evidence has suggested that magnesium sulfate infusion reduces delayed ischemic neurological deficit and improves clinical outcome after aneurysmal subarachnoid hemorrhage, A meta-analysis of current data suggests that magnesium sulfate infusion improves the outcome after aneurysmal subarachnoid hemorrhage through a reduction in delayed ischemic neurological deficit, Despite the publication of several randomized controlled studies, there is still much debate on whether magnesium sulfate improves outcome in patients with aneurysmal subarachnoid hemorrhage, Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed cerebral ischaemia[SEP]Relations: Magnesium sulfate has relations: contraindication with hypercalcemia disease, contraindication with hypercalcemia disease, contraindication with chronic diarrheal disease, contraindication with chronic diarrheal disease, contraindication with kidney disease, contraindication with kidney disease, drug_drug with Tubocurarine, drug_drug with Tubocurarine, drug_drug with Thioridazine, drug_drug with Thioridazine. Definitions: DCI defined as following: A noninvasive (noninfiltrating) carcinoma of the breast characterized by a proliferation of malignant epithelial cells confined to the mammary ducts or lobules, without light-microscopy evidence of invasion through the basement membrane into the surrounding stroma.. cerebral defined as following: The part of the brain that controls muscle functions and also controls speech, thought, emotions, reading, writing, and learning. The right hemisphere controls the muscles on the left side of the body, and the left hemisphere controls the muscles on the right side of the body.. MgSO4 defined as following: A small colorless crystal used as an anticonvulsant, a cathartic, and an electrolyte replenisher in the treatment of pre-eclampsia and eclampsia. It causes direct inhibition of action potentials in myometrial muscle cells. Excitation and contraction are uncoupled, which decreases the frequency and force of contractions. (From AMA Drug Evaluations Annual, 1992, p1083). cerebral infarction defined as following: The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).. subarachnoid hemorrhage defined as following: Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.. SAH defined as following: A Turkic language spoken by the Yakut people in the Sakha Republic in the Russian Federation.. GOS defined as following: A 6-item patient-reported outcome used to evaluate patient empowerment after they have received genetic counseling and testing services.. aneurysm rupture defined as following: The tearing or bursting of the weakened wall of the aneurysmal sac, usually heralded by sudden worsening pain. The great danger of a ruptured aneurysm is the large amount of blood spilling into the surrounding tissues and cavities, causing HEMORRHAGIC SHOCK.. nicardipine defined as following: A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents.. statins defined as following: Compounds that inhibit HYDROXYMETHYLGLUTARYL COA REDUCTASES. They have been shown to directly lower CHOLESTEROL synthesis.. neurological deficits defined as following: Loss of movement function.. CT defined as following: Tomography using x-ray transmission and a computer algorithm to reconstruct the image.. vasospasm defined as following: spasm of the blood vessels resulting in decrease in their caliber.. magnesium sulfate defined as following: A small colorless crystal used as an anticonvulsant, a cathartic, and an electrolyte replenisher in the treatment of pre-eclampsia and eclampsia. It causes direct inhibition of action potentials in myometrial muscle cells. Excitation and contraction are uncoupled, which decreases the frequency and force of contractions. (From AMA Drug Evaluations Annual, 1992, p1083).", "label": "no"} {"id": "converted_4112", "sentence1": "Is there a role for TFII-I in megakaryopoiesis?", "sentence2": "TFII-I/Gtf2i and Erythro-Megakaryopoiesis., TFII-I is a ubiquitously expressed transcription factor that positively or negatively regulates gene expression. TFII-I has been implicated in neuronal and immunologic diseases as well as in thymic epithelial cancer. Williams-Beuren Syndrome (WBS) is caused by a large hemizygous deletion on chromosome 7q11.23 which encompasses 26-28 genes, including GTF2I, the human gene encoding TFII-I. A subset of WBS patients has recently been shown to present with macrocytosis, a mild anemia characterized by enlarged erythrocytes. We conditionally deleted the TFII-I/Gtf2i gene in adult mice by tamoxifen induced Cre-recombination. Bone marrow cells revealed defects in erythro-megakaryopoiesis and an increase in expression of the adult β-globin gene. The data show that TFII-I acts as a repressor of β-globin gene transcription and that it is implicated in the differentiation of erythro-megakaryocytic cells.[SEP]Relations: GTF2I has relations: disease_protein with myeloid leukemia, disease_protein with myeloid leukemia, disease_protein with acute myeloid leukemia and myelodysplastic syndromes related to topoisomerase type 2 inhibitor, disease_protein with acute myeloid leukemia and myelodysplastic syndromes related to topoisomerase type 2 inhibitor, disease_protein with unclassified acute myeloid leukemia, disease_protein with unclassified acute myeloid leukemia, protein_protein with ZMYM3, protein_protein with ZMYM3, disease_protein with acute myeloid leukemia with t(6;9)(p23;q34), disease_protein with acute myeloid leukemia with t(6;9)(p23;q34). Definitions: Bone marrow cells defined as following: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.. WBS defined as following: A syndrome of multiple defects characterized primarily by umbilical hernia (HERNIA, UMBILICAL); MACROGLOSSIA; and GIGANTISM; and secondarily by visceromegaly; HYPOGLYCEMIA; and ear abnormalities.. tamoxifen defined as following: One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.. macrocytosis defined as following: An increase in nuclear size and amount of cytoplasm of a cell. The cells or nucleus may be slightly irregular and/or may be polyploid.. Williams-Beuren Syndrome defined as following: A disorder caused by hemizygous microdeletion of about 28 genes on chromosome 7q11.23, including the ELASTIN gene. Clinical manifestations include SUPRAVALVULAR AORTIC STENOSIS; MENTAL RETARDATION; elfin facies; impaired visuospatial constructive abilities; and transient HYPERCALCEMIA in infancy. The condition affects both sexes, with onset at birth or in early infancy.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"} {"id": "converted_4463", "sentence1": "Is EuroQol 5-Dimension Health Assessment (EQ-5D) [a widely used, simple instrument that monitors the general health-related quality of life (HRQoL) in chronic disease] a 5 question assessment?", "sentence2": "The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chronic disease. , OBJECTIVE: The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chronic disease., OBJECTIVE: The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chronic d, OBJECTIVE: The 6-question EuroQol 5-Dimension Health Assessment (EQ-5D) is a widely used, simple instrument that monitors general health-related quality of life (HRQoL) in chron[SEP]Relations: Chronic lung disease has relations: disease_phenotype_positive with severe acute respiratory syndrome, disease_phenotype_positive with severe acute respiratory syndrome, disease_phenotype_positive with alobar holoprosencephaly, disease_phenotype_positive with alobar holoprosencephaly, disease_phenotype_positive with cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome, disease_phenotype_positive with cognitive impairment - coarse facies - heart defects - obesity - pulmonary involvement - short stature - skeletal dysplasia syndrome, disease_phenotype_positive with combined immunodeficiency due to LRBA deficiency, disease_phenotype_positive with combined immunodeficiency due to LRBA deficiency, disease_phenotype_positive with toxic epidermal necrolysis, disease_phenotype_positive with toxic epidermal necrolysis. Definitions: chronic disease defined as following: Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2)..", "label": "no"} {"id": "converted_1952", "sentence1": "Can telomere length shortening be reversed by telomerase?", "sentence2": "Telomere length is regulated around an equilibrium set point. Telomeres shorten during replication and are lengthened by telomerase. Disruption of the length equilibrium leads to disease; thus, it is important to understand the mechanisms that regulate length at the molecular level. , High telomerase activity is detected in nearly all human cancers but most human cells are devoid of telomerase activity. There is well-documented evidence that reactivation of telomerase occurs during cellular transformation. In humans, tumors can rely in reactivation of telomerase or originate in a telomerase positive stem/progenitor cell, or rely in alternative lengthening of telomeres, a telomerase-independent telomere-length maintenance mechanism., Together, these observations may provoke a re-evaluation of telomere and telomerase based therapies, both in telomerase inhibition for cancer therapy and telomerase activation for tissue regeneration and anti-ageing strategies., Telomeres progressively shorten throughout life. A hallmark of advanced malignancies is the ability for continuous cell divisions that almost universally correlates with the stabilization of telomere length by the reactivation of telomerase., Telomerase-mediated telomere elongation provides cell populations with the ability to proliferate indefinitely. Telomerase is capable of recognizing and extending the shortest telomeres in cells;, Telomerase gene therapy rescues telomere length, bone marrow aplasia, and survival in mice with aplastic anemia.[SEP]Relations: Telomere Extension By Telomerase has relations: pathway_protein with TERT, pathway_protein with TERT, pathway_protein with ACD, pathway_protein with ACD, pathway_protein with RTEL1, pathway_protein with RTEL1, pathway_protein with TERF2, pathway_protein with TERF2, pathway_protein with GAR1, pathway_protein with GAR1. Definitions: Telomeres defined as following: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.. molecular defined as following: Relating to or produced by or consisting of molecules.. telomerase defined as following: An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.. humans defined as following: Members of the species Homo sapiens.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. aplastic anemia defined as following: A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. bone marrow aplasia defined as following: Depletion of stem cells in the bone marrow that results in the lack of production of hematopoietic cells.. telomere defined as following: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs..", "label": "yes"} {"id": "converted_856", "sentence1": "Is Dicer part of the RISC loading complex?", "sentence2": "Dicer is a component of the protein machinery (the RNA Induced Silencing Complex [RISC]) which is involved in catalyzing the formation of mature microRNAs from their precursors in the process of microRNA biogenesis., RNA-induced silencing complex (RISC) Proteins PACT, TRBP, and Dicer are SRA binding nuclear receptor coregulators., The cytoplasmic RNA-induced silencing complex (RISC) contains dsRNA binding proteins, including protein kinase RNA activator (PACT), transactivation response RNA binding protein (TRBP), and Dicer, that process pre-microRNAs into mature microRNAs (miRNAs) that target specific mRNA species for regulation. , Although the major RNAi pathway proteins are found in most subcellular compartments, the miRNA- and siRNA-loaded Ago2 populations co-sediment almost exclusively with the rER membranes, together with the RISC loading complex (RLC) factors Dicer, TAR RNA binding protein (TRBP) and protein activator of the interferon-induced protein kinase (PACT)., RNA interference (RNAi) is mediated by small interfering RNAs (siRNAs), which are liberated from double-stranded (ds)RNA precursors by Dicer and guide the RNA-induced silencing complex (RISC) to targets., . Dicer, an RNase III enzyme, plays a central role in the RNAi pathway by cleaving precursors of both of these classes of RNAs to form mature siRNAs and miRNAs, which are then loaded into the RNA-induced silencing complex (RISC). , Canonical siRNAs are 21 nucleotides (nt) in length and are loaded to the RNA Induced Silencing Complex when introduced into the cells, while longer siRNA molecules are first processed by endogenous Dicer and thus termed Dicer-substrate siRNA (DsiRNA). [SEP]Relations: protein binding has relations: molfunc_protein with DICER1, molfunc_protein with DICER1, molfunc_protein with ECSCR, molfunc_protein with ECSCR, molfunc_protein with RILP, molfunc_protein with RILP, molfunc_protein with TRIR, molfunc_protein with TRIR. chromatin silencing complex has relations: cellcomp_protein with RRP8, cellcomp_protein with RRP8. Definitions: RNAs defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). Dicer defined as following: Endoribonuclease Dicer (1922 aa, ~219 kDa) is encoded by the human DICER1 gene. This protein plays a role in both pri-miRNA processing and RNA interference.. RLC defined as following: Human ITGA9 wild-type allele is located in the vicinity of 3p22.2 and is approximately 371 kb in length. This allele, which encodes integrin alpha-9 protein, plays a role in cell adhesion-regulated signaling. Aberrant expression is associated with small cell lung cancers.. small interfering RNAs defined as following: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.. miRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. RISC defined as following: A RNA-protein complex that catalyzes facilitates the association of either a microRNA or a small interfering RNA with its complementary coding RNA and then degrades the targeted coding RNA molecule.. molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. nucleotides defined as following: The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed). cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. RNA binding protein defined as following: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.. TAR defined as following: A rare syndrome characterized by the presence of thrombocytopenia associated with bilateral absence of the radius bone.. Ago2 defined as following: Protein argonaute-2 (859 aa, ~97 kDa) is encoded by the human AGO2 gene. This protein plays a role in RNA catabolism..", "label": "yes"} {"id": "converted_2246", "sentence1": "Is NEMO a zinc finger protein?", "sentence2": "To better understand the thermodynamics and dynamics of the zinc finger of NEMO (NF-κB essential modulator), an alteration in the zinc finger domain of NEMO (K392R) , CYLD and the NEMO Zinc Finger Regulate Tumor Necrosis Factor Signaling and Early Embryogenesis., our simulations of the zinc finger NEMO, An important regulatory domain of NF-[Formula: see text]B Essential Modulator (NEMO) is a ubiquitin-binding zinc finger, with a tetrahedral CYS3HIS1 zinc-coordinating binding site., NEMO function is mediated by two distal ubiquitin binding domains located in the regulatory C-terminal domain of the protein: the coiled-coil 2-leucine zipper (CC2-LZ) domain and the zinc finger (ZF) domain. , We show here that the NEMO C terminus, comprising the ubiquitin binding region and a zinc finger,[SEP]Relations: C2H2 zinc finger domain binding has relations: molfunc_protein with EHMT1, molfunc_protein with EHMT1, molfunc_protein with EHMT2, molfunc_protein with EHMT2, molfunc_protein with GATA1, molfunc_protein with GATA1, molfunc_protein with LEF1, molfunc_protein with LEF1, molfunc_protein with THAP7, molfunc_protein with THAP7. Definitions: zinc finger defined as following: Motifs in DNA- and RNA-binding proteins whose amino acids are folded into a single structural unit around a zinc atom. In the classic zinc finger, one zinc atom is bound to two cysteines and two histidines. In between the cysteines and histidines are 12 residues which form a DNA binding fingertip. By variations in the composition of the sequences in the fingertip and the number and spacing of tandem repeats of the motif, zinc fingers can form a large number of different sequence specific binding sites.. NEMO defined as following: NF-kappa-B essential modulator (419 aa, ~48 kDa) is encoded by the human IKBKG gene. This protein plays a role in the mediation of signal transduction through protein phosphorylation.. domain defined as following: A taxonomic category above that of Kingdom.. CYLD defined as following: Ubiquitin carboxyl-terminal hydrolase CYLD (956 aa, ~107 kDa) is encoded by the human CYLD gene. This protein is involved in the mediation of protein deubiquitination and the regulation of the cell cycle.. binding site defined as following: A Binding Site Domain is a region of protein that physically interacts stereospecifically, and usually at high affinity, with a specific ligand, substrate, or a specific domain of some complex target biomolecule, such as a protein, lipid, carbohydrate, or nucleic acid. Typically, but not necessarily, the interaction results in protein conformational alteration and functional modification.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species..", "label": "yes"} {"id": "converted_1166", "sentence1": "Are CpG islands located close to housekeeping genes?", "sentence2": "our analysis indicates that the association of CGIs with housekeeping genes is not as strong as previously estimated, CpG islands are preferentially located at the start of transcription of housekeeping genes and are associated with tissue-specific genes, It has been envisaged that CpG islands are often observed near the transcriptional start sites (TSS) of housekeeping genes., These regions represent about 1% of genomic DNA and are generally found in the promoter region of housekeeping genes., CpG islands are stretches of DNA sequence that are enriched in the (CpG)n repeat and are present in close association with all housekeeping genes as well as some tissue-specific genes in the mammalian genome., CpG islands, which are found almost exclusively at the 5'-end of housekeeping genes, In housekeeping and many tissue-specific genes, the promoter is embedded in a so-called CpG island., All housekeeping and widely expressed genes have a CpG island covering the transcription start, whereas 40% of the genes with a tissue-specific or limited expression are associated with islands, Methylation-free CpG clusters, so-called HTF islands, are most often associated with the promoter regions of housekeeping genes, whereas genes expressed in a single-cell type are usually deficient in these sequences., Unmethylated CpG rich islands are a feature of vertebrate DNA: they are associated with housekeeping and many tissue specific genes., CpG islands were associated with the 5' ends of all housekeeping genes and many tissue-specific genes, and with the 3' ends of some tissue-specific genes.[SEP]Relations: GLI proteins bind promoters of Hh responsive genes to promote transcription has relations: pathway_protein with GLI2, pathway_protein with GLI2, pathway_protein with GLI3, pathway_protein with GLI3, pathway_protein with GLI1, pathway_protein with GLI1. promoter clearance from RNA polymerase I promoter has relations: bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance during DNA-templated transcription. toxic shock syndrome has relations: disease_protein with C5AR1, disease_protein with C5AR1. Definitions: promoter defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. TSS defined as following: A rare acute life-threatening systemic bacterial noncontagious illness caused by any of several related staphylococcal exotoxins. It is characterized by high fever, hypotension, rash, multi-organ dysfunction, and cutaneous desquamation during the early convalescent period. The toxins affect the host immune system, causing an exuberant and pathological host inflammatory response. Laboratory findings include leukocytosis, elevated prothrombin time, hypoalbuminemia, hypocalcemia, and pyuria.. genomic DNA defined as following: The DNA that is part of the normal chromosomal complement of an organism.. sequences defined as following: The sequence of nucleotide residues along a DNA chain.. promoter regions defined as following: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. islands defined as following: A land mass smaller than a continent that is surrounded by water.. housekeeping genes defined as following: Constitutively and evenly expressed genes involved in routine cellular metabolisms.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. CpG island defined as following: Areas of increased density of the dinucleotide sequence cytosine--phosphate diester--guanine. They form stretches of DNA several hundred to several thousand base pairs long. In humans there are about 45,000 CpG islands, mostly found at the 5' ends of genes. They are unmethylated except for those on the inactive X chromosome and some associated with imprinted genes..", "label": "yes"} {"id": "converted_3656", "sentence1": "Can Systemic Lupus Erythematosus cause seizures?", "sentence2": "The mean ± SD age at SLE diagnosis and at onset of PRES was 25.02 ± 13.78 and 28.31 ± 12.61 years, respectively. Seizure was the most common presenting symptom, as seen in 28 episodes, followed by acute severe headache in 17,, Epilepsy is characterized by a relevant epidemiological and clinical burden. In the extant literature, an increased risk of seizures has been described in several inflammatory/autoimmune disorders, including systemic lupus erythematosus (SLE)., Seizures are one of the most serious neuropsychiatric manifestations of systemic lupus erythematous (SLE). , The aim of this study was to describe the frequency , attribution , outcome and predictors of seizures in systemic lupus erythematosus ( SLE, OBJECTIVE\nTo evaluate the frequency and risk factors of epileptic seizures in a large cohort of patients with systemic lupus erythematosus (SLE)., Epileptic seizures occurred at the onset of SLE symptoms in 19 (31.6%) and after the onset of SLE in 41 of 60 (68.3%) patients., Epileptic seizures and EEG features in juvenile systemic lupus erythematosus., CONCLUSIONS\nEpileptic seizures were observed in 11.2% of systemic lupus erythematosus (SLE) patients., CONCLUSIONS\nSeizures tend to occur early in the course of systemic lupus erythematosus, and contribute to damage accrual., Seizures tend to occur early in the course of systemic lupus erythematosus, and contribute to damage accrual., To determine the factors associated with seizures in systemic lupus erythematosus (SLE)., Neurologic manifestations, in special epileptic seizures, are frequent in systemic lupus erythematosus.[SEP]Relations: Seizure has relations: disease_phenotype_positive with systemic lupus erythematosus (disease), disease_phenotype_positive with systemic lupus erythematosus (disease), disease_phenotype_positive with pediatric systemic lupus erythematosus, disease_phenotype_positive with pediatric systemic lupus erythematosus, drug_effect with Temsirolimus, drug_effect with Temsirolimus. bullous systemic lupus erythematosus has relations: disease_disease with lupus erythematosus, disease_disease with lupus erythematosus, disease_disease with systemic lupus erythematosus (disease), disease_disease with systemic lupus erythematosus (disease). Definitions: Epilepsy defined as following: A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313). EEG defined as following: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain.. SLE defined as following: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.. seizures defined as following: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\".", "label": "yes"} {"id": "converted_3210", "sentence1": "Are cardenolides inhibitors of Na+/K+ ATPase?", "sentence2": ". Previously, we reported that a variety of cardenolides impart anti-transmissible gastroenteritis coronavirus (TGEV) activity in swine testicular (ST) cells, through targeting of the cell membrane sodium/potassium pump, Na+/K+-ATPase. , : We found evidence for low cardenolides by HPLC, but substantial toxicity when extracts were assayed on Na+ /K+ -ATPases., Cardenolides have shown significant antitumor activity due to their ability to inhibit the Na+K+ATPase enzyme, and the expression of this enzyme is increased in tumor cells. [SEP]Relations: acellular membrane has relations: anatomy_anatomy with basal lamina of epithelium, anatomy_anatomy with basal lamina of epithelium, anatomy_anatomy with lamina lucida, anatomy_anatomy with lamina lucida, anatomy_anatomy with basement membrane of epithelium, anatomy_anatomy with basement membrane of epithelium, anatomy_anatomy with lamina densa of glomerular basement membrane, anatomy_anatomy with lamina densa of glomerular basement membrane. malignancy in giant cell tumor of bone has relations: disease_disease with malignant giant cell tumor, disease_disease with malignant giant cell tumor. Definitions: cell membrane defined as following: Any of the lipid bilayer membranes within a cell.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. tumor cells defined as following: Cells of, or derived from, a tumor.. coronavirus defined as following: A member of CORONAVIRIDAE which causes respiratory or gastrointestinal disease in a variety of vertebrates.. Cardenolides defined as following: C(23)-steroids with methyl groups at C-10 and C-13 and a five-membered lactone at C-17. They are aglycone constituents of CARDIAC GLYCOSIDES and must have at least one double bond in the molecule. The class includes cardadienolides and cardatrienolides. Members include DIGITOXIN and DIGOXIN and their derivatives and the STROPHANTHINS.. swine defined as following: A species of SWINE, in the family Suidae, comprising a number of subspecies including the domestic pig Sus scrofa domestica.. cardenolides defined as following: C(23)-steroids with methyl groups at C-10 and C-13 and a five-membered lactone at C-17. They are aglycone constituents of CARDIAC GLYCOSIDES and must have at least one double bond in the molecule. The class includes cardadienolides and cardatrienolides. Members include DIGITOXIN and DIGOXIN and their derivatives and the STROPHANTHINS..", "label": "yes"} {"id": "converted_2410", "sentence1": "Is overproduction of transthyretin is associated with amyloidosis associated neuropathy?", "sentence2": "Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) is a disease caused by the deposit of abnormal transthyretin on tissues, mainly nerves, transthyretin familial amyloid polyneuropathy, We report a new transthyretin (ATTR) gene c.272C>G mutation and variant protein, p.Leu32Val, in a kindred of Bolivian origin with a rapid progressive peripheral neuropathy and cardiomyopat, Hereditary transthyretin amyloidosis is an autosomal dominant inherited disorder, first described in families with sensorimotor and autonomic neuropathy., Abnormal deposition of aggregated wild-type (WT) human transthyretin (TTR) and its pathogenic variants is responsible for cardiomyopathy and neuropathy related to TTR amyloidosis. , Transthyretin (TTR), normally a plasma circulating protein, can become misfolded and aggregated, ultimately leading to extracellular deposition of amyloid fibrils usually targeted to heart or nerve tissues. Referred to as TTR-associated amyloidoses (ATTR), this group of diseases is frequently life threatening and fatal if untreated, Hereditary transthyretin amyloidosis is an autosomal dominant inherited disorder, first described in families with sensorimotor and autonomic neuropathy., Hereditary transthyretin amyloidosis (ATTR) is usually characterised by a progressive peripheral and autonomic neuropathy often with associated cardiac failure and is due to dominantly inherited transthyretin mutations causing accelerated amyloid deposition.[SEP]Relations: hereditary ATTR amyloidosis has relations: disease_disease with familial amyloid neuropathy, disease_disease with familial amyloid neuropathy, disease_disease with hereditary amyloidosis, disease_disease with hereditary amyloidosis. Optic neuropathy has relations: disease_phenotype_positive with fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3, disease_phenotype_positive with fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3, disease_phenotype_positive with combined oxidative phosphorylation deficiency, disease_phenotype_positive with combined oxidative phosphorylation deficiency. Cardiomyopathy has relations: disease_phenotype_positive with familial amyloid neuropathy, disease_phenotype_positive with familial amyloid neuropathy. Definitions: peripheral neuropathy defined as following: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.. nerve tissues defined as following: Differentiated tissue of the central nervous system composed of NERVE CELLS, fibers, DENDRITES, and specialized supporting cells.. amyloid defined as following: A family of apolipoproteins that are associated with high-density lipoprotein particles in the serum. These proteins may play a role in both the acute-phase of inflammation and in cholesterol transport.. cardiomyopathy defined as following: A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).. TTR defined as following: Transthyretin (147 aa, ~16 kDa) is encoded by the human TTR gene. This protein is involved in both the binding and transport of retinol and thyroxine.. cardiac failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. amyloidosis defined as following: A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. Various signs and symptoms depend on the location and size of the deposits.. peripheral defined as following: On or near an edge or constituting an outer boundary; the outer area.. variant protein defined as following: A protein with an amino acid sequence that differs from the wildtype, canonical sequence.. Transthyretin defined as following: A tetrameric protein, molecular weight between 50,000 and 70,000, consisting of 4 equal chains, and migrating on electrophoresis in 3 fractions more mobile than serum albumin. Its concentration ranges from 7 to 33 per cent in the serum, but levels decrease in liver disease.. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. nerves defined as following: Part of the peripheral nervous system composed of bundles of nerve fibers running to various organs and tissues of the body using chemical and electrical signals to transmit sensory and motor information from one body part to another.. ATTR defined as following: Human TTR wild-type allele is located in the vicinity of 18q12.1 and is approximately 7 kb in length. This allele, which encodes transthyretin protein, plays a role in the stabilization and transport of thyroxine and retinol. Mutations in the gene are associated with hyperthyroxinemia and amyloidosis types 1 and 7.. extracellular defined as following: The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite. [GOC:go_curators]. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. neuropathy defined as following: A disorder affecting the cranial nerves or the peripheral nervous system. It manifests with pain, tingling, numbness, and muscle weakness. It may be the result of physical injury, toxic substances, viral diseases, diabetes, renal failure, cancer, and drugs.. autonomic neuropathy defined as following: An inherited or acquired peripheral neuropathy affecting the autonomic nervous system. It results in disruption of the involuntary body functions. Inherited causes include Fabry disease and porphyrias. Acquired causes include diabetes, uremia, hepatic disorders, vitamin deficiencies, toxins, and drug toxicities.. transthyretin defined as following: A tetrameric protein, molecular weight between 50,000 and 70,000, consisting of 4 equal chains, and migrating on electrophoresis in 3 fractions more mobile than serum albumin. Its concentration ranges from 7 to 33 per cent in the serum, but levels decrease in liver disease..", "label": "yes"} {"id": "converted_758", "sentence1": "Is PLK2 involved in alpha-synuclein phosphorylation in the nervous system?", "sentence2": "Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system, Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons, PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay, Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo, specific knockdown of PLK2 expression by transduction with short hairpin RNA constructs or by knock-out of the plk2 gene reduced p-Ser-129 levels, These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system., These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system., Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons., Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system., PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay., Two of these kinases stand out as potential drug targets for novel PD therapy, namely leucine rich repeat kinase 2 (LRRK2) and the alpha-synuclein (α-syn) phosphorylating polo-like kinase 2 (PLK2)., Also, due to the dominant mode of α-syn and LRRK2 inheritance and based on current knowledge of LRRK2 and α-syn phosphorylation by PLK2, inhibition of LRRK2 and PLK2 may constitute a potential therapy for PD., To better understand the role of PLK2 in α-synuclein phosphorylation in vivo, we further evaluated the effect of PLK2 genetic knockdown and pharmacological inhibition on Phospho-α-Syn levels in different brain regions of PLK2 knockout (KO), heterozygous (Het) and wild-type (WT) mice., This PLK2-mediated neuroprotective effect is also dependent on PLK2 activity and α-synuclein phosphorylation., PLK2-mediated degradation of α-synuclein requires both phosphorylation at S129 and PLK2/α-synuclein complex formation., Overexpression of only PLK2 increased phosphorylation of aggregated α-syn at S129, which likely is due to increased phosphorylation of soluble α-syn, which then was incorporated into aggregates., Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons., PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay., Unlike other kinases reported to partially phosphorylate alpha-syn at Ser-129 in vitro, phosphorylation by PLK2 and PLK3 is quantitative (, Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo., These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system, Inhibitors of PLK kinases inhibited alpha-synuclein phosphorylation both in primary cortical cell cultures and in mouse brain in vivo, PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay, To better understand the role of PLK2 in α-synuclein phosphorylation in vivo, we further evaluated the effect of PLK2 genetic knockdown and pharmacological inhibition on Phospho-α-Syn levels in different brain regions of PLK2 knockout (KO), heterozygous (Het) and wild-type (WT) mice, Polo-like kinase-2 (Plk-2) has been implicated as the dominant kinase involved in the phosphorylation of α-synuclein in Lewy bodies, which are one of the hallmarks of Parkinson's disease neuropathology[SEP]Relations: Parkinson disease has relations: disease_protein with LRRK2, disease_protein with LRRK2, disease_protein with CNTNAP2, disease_protein with CNTNAP2. ELL has relations: molfunc_protein with phosphatase binding, molfunc_protein with phosphatase binding, protein_protein with PIP4K2A, protein_protein with PIP4K2A, protein_protein with POU2F2, protein_protein with POU2F2. Definitions: Plk-2 defined as following: Serine/threonine-protein kinase PLK2 (685 aa, ~78 kDa) is encoded by the human PLK2 gene. This protein is involved in cell cycle progression, centriole duplication and serine/threonine phosphorylation.. serine defined as following: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. PLK3 defined as following: Serine/threonine-protein kinase PLK3 (646 aa, ~72 kDa) is encoded by the human PLK3 gene. This protein is involved in protein phosphorylation and cell cycle regulation.. alpha-synuclein defined as following: A synuclein that is a major component of LEWY BODIES and plays a role in SYNUCLEINOPATHIES, neurodegeneration and neuroprotection.. LRRK2 defined as following: Leucine-rich repeat serine/threonine-protein kinase 2 (2527 aa, ~286 kDa) is encoded by the human LRRK2 gene. This protein may play a role in protein phosphorylation.. Polo-like kinase 2 defined as following: This gene is involved in normal cell division.. leucine rich repeat kinase 2 defined as following: Leucine-rich repeat serine/threonine-protein kinase 1 (2015 aa, ~225 kDa) is encoded by the human LRRK1 gene. This protein is involved in serine/threonine phosphorylation and osteoclast resorption of bone.. Parkinson's disease defined as following: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75). polo-like kinase 2 defined as following: This gene plays a role in mitotic regulation.. PD defined as following: A score of 4 or 5 on a 5-point PET scale with an increase in intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment.. PLK defined as following: Serine/threonine-protein kinase PLK1 (603 aa, ~68 kDa) is encoded by the human PLK1 gene. This protein is involved in protein phosphorylation and the regulation of both cell cycle progression and cytokinesis.. PLK2 defined as following: This gene is involved in normal cell division..", "label": "yes"} {"id": "converted_813", "sentence1": "Does a selective sweep increase genetic variation?", "sentence2": "An East African population that gave rise to non-Africans underwent a selective sweep affecting the subcentromeric region where MTMR8 is located. This and similar sweeps in four other regions of the X chromosome, documented in the literature, effectively reduced genetic diversity of non-African chromosomes, a selective sweep that has removed genetic variation from much of the drive X chromosome., evidence of reduced diversity and an excess of fixed replacement sites, consistent with a species-wide selective sweep., recent independent selective sweeps in AGO2 have reduced genetic variation, episodes of natural selection (likely a selective sweep) predating the coalescent of human lineages, within the last 25 million years, account for the observed reduced diversity, reduced variation or deviations from neutrality that might indicate a recent selective sweep, Consider a genetic locus carrying a strongly beneficial allele which has recently fixed in a large population. As strongly beneficial alleles fix quickly, sequence diversity at partially linked neutral loci is reduced. This phenomenon is known as a selective sweep., a local selective sweep or demographic process that reduced variability, reduced variation (a selective sweep), the mtDNA diversity, but not the nuclear DNA diversity, has been reduced relative to the neutral expectation of molecular evolution, suggesting the action of a selective sweep, Furthermore, the amount of genetic variation after a selective sweep is expected to be unequal over demes: a greater reduction in expected heterozygosity occurs in the subpopulation from which the beneficial mutation originates than in its neighboring subpopulations., Our observation of reduction in variation at both intragenic and flanking loci of mutant pfcrt gene confirmed the selective sweep model of natural selection in chloroquine resistant P., A selective sweep describes the reduction of linked genetic variation due to strong positive selection., In these situations, adaptation should commonly produce 'soft' selective sweeps, where multiple adaptive alleles sweep through the population at the same time, either because the alleles were already present as standing genetic variation or arose independently by recurrent de novo mutations., CONCLUSIONS: The severe reduction in nucleotide variation at OsAMT1;1 in rice was caused by a selective sweep around OsAMT1;1, which may reflect the nitrogen uptake system under strong selection by the paddy soil during the domestication of rice., A selective sweep describes the reduction of linked genetic variation due to strong positive selection[SEP]Relations: adaptation to pheromone regulating conjugation with mutual genetic exchange has relations: bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with regulation of conjugation, bioprocess_bioprocess with regulation of conjugation, bioprocess_bioprocess with negative adaptation of signaling pathway, bioprocess_bioprocess with negative adaptation of signaling pathway. Lacrimation abnormality has relations: phenotype_phenotype with Decreased lacrimation, phenotype_phenotype with Decreased lacrimation, phenotype_phenotype with Gustatory lacrimation, phenotype_phenotype with Gustatory lacrimation. Definitions: AGO2 defined as following: Protein argonaute-2 (859 aa, ~97 kDa) is encoded by the human AGO2 gene. This protein plays a role in RNA catabolism.. allele defined as following: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.. human defined as following: Members of the species Homo sapiens.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. mtDNA defined as following: Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. genetic locus defined as following: Specific regions that are mapped within a GENOME. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of CHROMOSOME 6. Many well known genetic loci are also known by common names that are associated with a genetic function or HEREDITARY DISEASE.. X chromosome defined as following: The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species..", "label": "no"} {"id": "converted_2454", "sentence1": "Does the human lncRNA LINC-PINT promote tumorigenesis?", "sentence2": "The human lncRNA LINC-PINT inhibits tumor cell invasion through a highly conserved sequence element., Here we characterize the function of the p53-regulated human lncRNA LINC-PINT in cancer. We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells. A cross-species analysis identifies a highly conserved sequence element in LINC-PINT that is essential for its function. This sequence mediates a specific interaction with PRC2, necessary for the LINC-PINT-dependent repression of a pro-invasion signature of genes regulated by the transcription factor EGR1., We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells., These results thus indicate that low plasma Linc-pint expression could serve as a minimally invasive biomarker for early PCa detection, and that low Linc-pint levels in PCa tumors could be used for predicting patient prognosis., Our data demonstrate that Linc-pint expression is lower in plasma samples from PCa patients than from healthy individuals, and indicate that plasma Linc-pint levels are more sensitive than CA19-9 for detecting PCa., Low plasma Linc-pint levels correlate with tumor recurrence, while low tumor Linc-pint levels correlate with poor prognosis for PCa patients after pancreatectomy., We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells., We find that LINC-PINT is downregulated in multiple types of cancer and acts as a tumor suppressor lncRNA by reducing the invasive phenotype of cancer cells., These results thus indicate that low plasma Linc-pint expression could serve as a minimally invasive biomarker for early PCa detection, and that low Linc-pint levels in PCa tumors could be used for predicting patient prognosis.Deciduous maxillary right first molar tooth; Universal designation B; ISO designation 54
. autoantibodies defined as following: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.. Fingolimod defined as following: An orally available derivate of myriocin and sphingosine-1-phosphate receptor 1 (S1PR1, S1P1) modulator, with potential anti-inflammatory and immunomodulating activities. Upon oral administration, fingolimod, as a structural analogue of sphingosine, selectively targets and binds to S1PR1 on lymphocytes and causes transient receptor activation followed by S1PR1 internalization and degradation. This results in the sequestration of lymphocytes in lymph nodes. By preventing egress of lymphocytes. fingolimod reduces both the amount of circulating peripheral lymphocytes and the infiltration of lymphocytes into target tissues. This prevents a lymphocyte-mediated immune response and may reduce inflammation. S1PR1, a G-protein coupled receptor, plays a key role in lymphocyte migration from lymphoid tissues. Fingolimod also shifts macrophages to an anti-inflammatory M2 phenotype, and modulates their proliferation, morphology, and cytokine release via inhibition of the transient receptor potential cation channel, subfamily M, member 7 (TRPM7).. myelin defined as following: The lipid-rich sheath surrounding AXONS in both the CENTRAL NERVOUS SYSTEMS and PERIPHERAL NERVOUS SYSTEM. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (SCHWANN CELLS in the peripheral and OLIGODENDROGLIA in the central nervous system). Deterioration of the sheath in DEMYELINATING DISEASES is a serious clinical problem.. demyelination defined as following: A loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system. [HPO:probinson]. primary immunodeficiencies defined as following: Immunodeficiency disease that arises independent of another pathologic process, disease, or injury.. CD24 defined as following: A GPI-linked cell adhesion protein originally identified as a heat stable antigen in mice. It mediates antigen-dependent activation and proliferation of B-CELLS. It is also involved in METASTASIS and is highly expressed in many NEOPLASMS.. autoimmune diseases defined as following: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.. B cells defined as following: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.. plasma cells defined as following: Specialized forms of antibody-producing B-LYMPHOCYTES. They synthesize and secrete immunoglobulin. They are found only in lymphoid organs and at sites of immune responses and normally do not circulate in the blood or lymph. (Rosen et al., Dictionary of Immunology, 1989, p169 & Abbas et al., Cellular and Molecular Immunology, 2d ed, p20). chronic lymphocytic leukemia defined as following: A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.. multiple sclerosis defined as following: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903). cerebrospinal fluid defined as following: A watery fluid that is continuously produced in the CHOROID PLEXUS and circulates around the surface of the BRAIN; SPINAL CORD; and in the CEREBRAL VENTRICLES.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. immunoglobulins defined as following: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.. neurodegeneration defined as following: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.. microglia defined as following: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling..", "label": "yes"} {"id": "converted_129", "sentence1": "Is amantadine effective for treatment of disorders conciousness?", "sentence2": "We here provide a systematic overview of the therapeutic effects of amantadine, apomorphine and zolpidem in patients recovering from coma. Evidence from clinical trials using these commonly prescribed pharmacological agents suggests positive changes in the neurological status in patients, leading sometimes to dramatic improvements., Pharmaceuticals that act in the oxygen based amino acid systems of the brain include the GABAergic medications zolpidem and baclofen, while those that act in the monoamine axes include the dopaminergic medications L Dopa, amantadine, bromocriptine, apomorphine and methylphenidate, and the noradrenergic and serotonergic medications desipramine, amitriptyline, protriptyline and fluoxetine. , Sporadic cases of recovery from a DOC have been reported after the administration of various pharmacological agents (baclofen, zolpidem, amantadine etc.)., Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery., During the 4-week treatment period, recovery was significantly faster in the amantadine group than in the placebo group, as measured by the DRS score (difference in slope, 0.24 points per week; P=0.007), indicating a benefit with respect to the primary outcome measure. , Amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness., Sporadic cases of dramatic recovery from DOC after the administration of various pharmacological agents, such as baclofen, zolpidem and amantadine, have been recently supported by intriguing scientific observations. , According to the 16 eligible studies, medical management by dopaminergic agents (levodopa, amantadine), zolpidem and median nerve stimulation, or surgical management by deep brain stimulation, extradural cortical stimulation, spinal cord stimulation and intrathecal baclofen have shown to improve the level of consciousness in certain cases. , Higher exposure of amantadine (average concentration of amantadine during 6 mg/kg/day > 1.5 mg/L) may be associated with better recovery of consciousness. , Based on the preliminary data, higher dosing may be considered in the setting of brain injury., Patients treated with PK-Merz exhibited the more significant restoration of consciousness and better dynamics (regress) of neurological deficit with the most intensive restoration of neurological deficit in the first day that allows to recommend the use of amantadine sulfate in the first hours of ischemic stroke and for the prevention of reperfusion damage in recanalisation therapy of ischemic stroke., There was no significant difference in the slopes of recovery during either arm for the Coma/Near-Coma Scale (P = 0.24) or the Coma Recovery Scale-Revised (P = 0.28), although improvements in consciousness were noted by the physician during weeks when amantadine was given (P = 0.02). , This study suggests that amantadine facilitates recovery of consciousness in pediatric acquired brain injury and provides important information necessary to design future more definitive studies., The study has shown a positive effect of this drug at coma emergence, which manifested itself as clinical improvement and a better outcome of the disease., This article will review the evidence for the use of psychostimulants (methylphenidate), antidepressants (amitriptyline, selective serotonin reuptake inhibitors, and buproprion), Parkinson's medications (amantadine, bromocriptine, carbidopa/levodopa), anticonvulsants (valproic acid), modafinil (Provigil), lactate, hyperbaric oxygen chamber, electroconvulsive therapy, and transmagnetic stimulation, in patients following a head injury., Of the psychoactive medications, amantadine hydrochloride was associated with greater recovery and dantrolene sodium was associated with less recovery, in terms of the DRS score at 16 weeks but not the time until commands were followed.[SEP]Relations: Amantadine has relations: contraindication with mental disorder, contraindication with mental disorder, contraindication with mental disorder, contraindication with mental disorder, contraindication with substance-related disorder, contraindication with substance-related disorder, contraindication with substance-related disorder, contraindication with substance-related disorder, contraindication with psychotic disorder, contraindication with psychotic disorder. Definitions: amantadine hydrochloride defined as following: The hydrochloride salt of amantadine, a synthetic tricyclic amine with antiviral, antiparkinsonian, and antihyperalgesic activities. Amantadine appears to exert its antiviral effect against the influenza A virus by interfering with the function of the transmembrane domain of the viral M2 protein, thereby preventing the release of infectious viral nucleic acids into host cells; furthermore, this agent prevents virus assembly during virus replication. Amantadine exerts its antiparkinsonian effects by stimulating the release of dopamine from striatal dopaminergic nerve terminals and inhibiting its pre-synaptic reuptake. This agent may also exert some anticholinergic effect through inhibition of N-methyl-D-aspartic acid (NMDA) receptor-mediated stimulation of acetylcholine, resulting in antihyperalgesia.. baclofen defined as following: A GAMMA-AMINOBUTYRIC ACID derivative that is a specific agonist of GABA-B RECEPTORS. It is used in the treatment of MUSCLE SPASTICITY, especially that due to SPINAL CORD INJURIES. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission.. Amantadine defined as following: An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake.. protriptyline defined as following: Tricyclic antidepressant similar in action and side effects to IMIPRAMINE. It may produce excitation.. amantadine sulfate defined as following: The sulfate salt of amantadine, a synthetic tricyclic amine with antiviral, antiparkinsonian, and antihyperalgesic activities. Amantadine appears to exert its antiviral effect against the influenza A virus by interfering with the function of the transmembrane domain of the viral M2 protein, thereby preventing the release of infectious viral nucleic acids into host cells; furthermore, this agent prevents virus assembly during virus replication. Amantadine exerts its antiparkinsonian effects by stimulating the release of dopamine from striatal dopaminergic nerve terminals and inhibiting its pre-synaptic reuptake. This agent may also exert some anticholinergic effect through inhibition of N-methyl-D-aspartic acid (NMDA) receptor-mediated stimulation of acetylcholine, resulting in antihyperalgesia.. modafinil defined as following: A benzhydryl acetamide compound, central nervous system stimulant, and CYP3A4 inducing agent that is used in the treatment of NARCOLEPSY and SLEEP WAKE DISORDERS.. carbidopa/levodopa defined as following: An orally available combination of carbidopa, an inhibitor of aromatic amino acid decarboxylation, and levodopa, an inert, metabolic precursor to dopamine, with dopaminergic and antiparkinsonian properties. Upon oral administration, levodopa crosses the blood-brain barrier (BBB) and is decarboxylated to dopamine via dopa decarboxylase in the brain, promoting increased activation of dopamine receptors. Carbidopa inhibits dopa decarboxylase in the periphery, thereby preventing decarboxylation of levodopa in extracerebral tissues and increasing the delivery of dopamine to the central nervous system (CNS). As carbidopa does not cross the BBB, it does not interfere with CNS levodopa metabolism.. brain injury defined as following: Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.. lactate defined as following: The determination of the amount of lactic acid present in a sample.. levodopa defined as following: The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.. drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. traumatic brain injury defined as following: A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.. ischemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue.. amitriptyline defined as following: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines.. zolpidem defined as following: An imidazopyridine derivative and short-acting GABA-A receptor agonist that is used for the treatment of INSOMNIA.. bromocriptine defined as following: A semisynthetic ergotamine alkaloid that is a dopamine D2 agonist. It suppresses prolactin secretion.. neurological deficit defined as following: Loss of movement function.. apomorphine defined as following: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use.. fluoxetine defined as following: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.. valproic acid defined as following: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.. dopaminergic agents defined as following: Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.. antidepressants defined as following: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.. head injury defined as following: Traumatic injuries involving the cranium and intracranial structures (i.e., BRAIN; CRANIAL NERVES; MENINGES; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage.. methylphenidate defined as following: A central nervous system stimulant used most commonly in the treatment of ATTENTION DEFICIT DISORDER in children and for NARCOLEPSY. Its mechanisms appear to be similar to those of DEXTROAMPHETAMINE. The d-isomer of this drug is referred to as DEXMETHYLPHENIDATE HYDROCHLORIDE.. dantrolene sodium defined as following: The sodium salt form of dantrolene, a hydantoin derivative and direct-acting skeletal muscle relaxant. Dantrolene depresses excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor 1, and decreasing intracellular calcium concentration. Ryanodine receptors mediate the release of calcium from the sarcoplasmic reticulum, an essential step in muscle contraction.. reperfusion damage defined as following: Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA.. coma defined as following: Ocular motor apraxia, Cogan type is characterised by impairment of voluntary horizontal eye movements and compensatory head thrust. Around 50 cases have been described so far. The oculomotor manifestations tend to improve with age but the syndrome may also be associated with learning and speech difficulties, or, in some cases, cerebral malformations. Both sporadic and familial forms have been described, with sporadic forms being more frequent. The mode of transmission of the familial form has not yet been clearly established. A gene located on the long arm of chromosome 2, near to the <i>NPHP1</i> gene involved in nephronophthisis, may be associated with ocular motor apraxia, Cogan type.. amantadine defined as following: An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake..", "label": "yes"} {"id": "converted_3677", "sentence1": "Has the Spanich flu virus been reconstructed?", "sentence2": "Reconstruction of the 1918 influenza virus has facilitated considerable advancements in our understanding of this extraordinary pandemic virus., These viral RNA sequences eventually permitted reconstruction of the complete 1918 virus, which has yielded, almost a century after the deaths of its victims, novel insights into influenza virus biology and pathogenesis and has provided important information about how to prevent and control future pandemics., Reconstruction of the 1918 virus and studies elucidating the exceptional virulence and transmissibility of the virus are providing exciting new insights into this devastating pandemic strain. [SEP]Relations: Cessation of head growth has relations: disease_phenotype_positive with leukoencephalopathy with vanishing white matter, disease_phenotype_positive with leukoencephalopathy with vanishing white matter, disease_phenotype_positive with Angelman syndrome due to a point mutation, disease_phenotype_positive with Angelman syndrome due to a point mutation, disease_phenotype_positive with Angelman syndrome due to paternal uniparental disomy of chromosome 15, disease_phenotype_positive with Angelman syndrome due to paternal uniparental disomy of chromosome 15, disease_phenotype_positive with Angelman syndrome due to maternal 15q11q13 deletion, disease_phenotype_positive with Angelman syndrome due to maternal 15q11q13 deletion, disease_phenotype_positive with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, disease_phenotype_positive with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies. Definitions: virus defined as following: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells.. deaths defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions..", "label": "yes"} {"id": "converted_3712", "sentence1": "Are stem cell transplants used to treat acute kidney injury?", "sentence2": "Animal studies have shown that mesenchymal stromal cell (MSC) infusions improve acute kidney injury (AKI) outcomes when administered early after ischemic/reperfusion injury or within 24 hours after cisplatin administration., Early Diagnostic Markers for Detection of Acute Kidney Injury in Allogeneic Hematopoietic Stem Cell Transplant Recipients., Risk assessment for acute kidney injury after allogeneic hematopoietic stem cell transplantation based on Acute Kidney Injury Network criteria.[SEP]Relations: acute kidney failure has relations: disease_disease with acute disease, disease_disease with acute disease, disease_disease with kidney failure, disease_disease with kidney failure, disease_disease with acute kidney tubular necrosis, disease_disease with acute kidney tubular necrosis, disease_protein with INS, disease_protein with INS. Cisplatin has relations: drug_effect with Acute kidney injury, drug_effect with Acute kidney injury. Definitions: Hematopoietic Stem Cell defined as following: Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood.. MSC defined as following: A naturally occurring organoselenium compound found in many plants, including garlic, onions, and broccoli, with potential antioxidant and chemopreventive activities. Se-Methyl-seleno-L-cysteine (MSC) is an amino acid analogue of cysteine in which a methylselenium moiety replaces the sulphur atom of cysteine. This agent acts as an antioxidant when incorporated into glutathione peroxidase and has been shown to exhibit potent chemopreventive activity in animal models.. cisplatin defined as following: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.. mesenchymal stromal cell defined as following: Non-hematopoietic cells that support HEMATOPOIETIC STEM CELLS in bone marrow. They have also been isolated from other organs and tissues such as adipose tissue, UMBILICAL CORD BLOOD, and WHARTON JELLY and include a subpopulation of multipotent stem cells.. acute kidney injury defined as following: Sudden and sustained deterioration of the kidney function characterized by decreased glomerular filtration rate, increased serum creatinine or oliguria..", "label": "yes"} {"id": "converted_957", "sentence1": "Is selenium deficiency involved in autoimmune thyroid disease?", "sentence2": "In areas with severe selenium deficiency higher incidence of thyroiditis has been reported due to a decreased activity of selenium-dependent glutathione peroxidase enzyme within thyroid cells, Of 30 patients in the selenium treated group, 6 patients were overtly hypothyroid, 15 were subclinical hypothyroid, 6 were euthyroid, and 3 were subclinical hyperthyroid. The mean TPOAb concentration decreased significantly by 49.5% (P < 0.013) in the selenium treated group versus 10.1% (P < 0.95) in the placebo-treated group, Selenium substitution has a significant impact on inflammatory activity in thyroid-specific autoimmune disease, Serum selenium is low in newly diagnosed Graves' disease, S-Se was lower in patients with GD than in controls (mean (SD), GD: 89·9 μg/l (18·4); controls: 98·8 μg/l (19·7), P < 0·01), Patients with newly diagnosed GD and AIH had significantly lower s-Se compared with random controls. Our observation supports the postulated link between inadequate selenium supply and overt autoimmune thyroid disease, especially GD, Selenium deficiency is likely to constitute a risk factor for a feedforward derangement of the immune system-thyroid interaction, while selenium supplementation appears to dampen the self-amplifying nature of this derailed interaction, The recent recognition that the essential trace element selenium is incorporated as selenocysteine in all three deiodinases has decisively confirmed the clear-cut link between selenium and thyroid function. It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease, Maintenance of \"selenostasis\" via optimal intake not only aids preservation of general health but also contributes substantially to the prevention of thyroid disease, Low birth weight, iodine excess and deficiency, selenium deficiency, parity, oral contraceptive use, reproductive span, fetal microchimerism, stress, seasonal variation, allergy, smoking, radiation damage to the thyroid gland, viral and bacterial infections all play a role in the development of autoimmune thyroid disorders, It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease., Selenium deficiency may play an important role in the initiation and progression of autoimmune thyroid disease., [Selenium deficiency in celiac disease: risk of autoimmune thyroid diseases]., Low birth weight, iodine excess and deficiency, selenium deficiency, parity, oral contraceptive use, reproductive span, fetal microchimerism, stress, seasonal variation, allergy, smoking, radiation damage to the thyroid gland, viral and bacterial infections all play a role in the development of autoimmune thyroid disorders., Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined., Our observation supports the postulated link between inadequate selenium supply and overt autoimmune thyroid disease, especially GD., Selenium deficiency in celiac disease: risk of autoimmune thyroid diseases]., Selenoproteins contain the essential trace element selenium whose deficiency leads to major disorders including cancer, male reproductive system failure, or autoimmune thyroid disease., It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease., EVIDENCE SYNTHESIS: Evidence in support of selenium supplementation in thyroid autoimmune disease is evaluated, the results herein presented demonstrating the potential effectiveness of selenium in reducing the antithyroid peroxidase titer and improving the echostructure in the ultrasound examination., Some investigators suggest that selenium may be a useful adjunctive treatment for autoimmune thyroid diseases, such as Hashimoto and Graves' disease., Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases., Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined., Some clinical studies have demonstrated that selenium-deficient patients with autoimmune thyroid disease benefit from selenium supplementation, although the data are conflicting and many parameters must still be defined, High prevalence of hyperplastic and autoimmune diseases of thyroid in Ukrainian population is determined by endemic deficit of iodine and selenium, It has additionally been established that the thyroid contains more selenium than any other tissue and that selenium deficiency aggravates the manifestation of endemic myxedematous cretinism and autoimmune thyroid disease., Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases, Some investigators suggest that selenium may be a useful adjunctive treatment for autoimmune thyroid diseases, such as Hashimoto and Graves' disease[SEP]Relations: autoimmune thyroid disease has relations: disease_disease with thyroiditis (disease), disease_disease with thyroiditis (disease), disease_disease with atrophic thyroiditis, disease_disease with atrophic thyroiditis, disease_disease with Graves disease, disease_disease with Graves disease, disease_protein with TG, disease_protein with TG, disease_disease with autoimmune disease of endocrine system, disease_disease with autoimmune disease of endocrine system. Definitions: AIH defined as following: Hepatitis caused by autoantibodies. Drugs, infections, and toxins may trigger the production of the autoantibodies against the liver parenchyma.. cancer defined as following: A malignant tumor at the original site of growth.. selenocysteine defined as following: A naturally occurring amino acid in both eukaryotic and prokaryotic organisms. It is found in tRNAs and in the catalytic site of some enzymes. The genes for glutathione peroxidase and formate dehydrogenase contain the TGA codon, which codes for this amino acid.. Selenoproteins defined as following: Selenoproteins are proteins that specifically incorporate SELENOCYSTEINE into their amino acid chain. Most selenoproteins are enzymes with the selenocysteine residues being responsible for their catalytic functions.. hyperplastic defined as following: An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells.. iodine defined as following: homeopathic drug. Graves' disease defined as following: Hyperthyroidism associated with diffuse hyperplasia of the thyroid gland (goiter), resulting from production of antibodies that are directed against the thyrotropin receptor complex of the follicular epithelial cells. As a result, the thyroid gland enlarges and secretes increased amounts of thyroid hormones.. thyroid disease defined as following: Pathological processes involving the THYROID GLAND.. hypothyroid defined as following: A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction.. thyroiditis defined as following: Inflammatory diseases of the THYROID GLAND. Thyroiditis can be classified into acute (THYROIDITIS, SUPPURATIVE), subacute (granulomatous and lymphocytic), chronic fibrous (Riedel's), chronic lymphocytic (HASHIMOTO DISEASE), transient (POSTPARTUM THYROIDITIS), and other AUTOIMMUNE THYROIDITIS subtypes.. celiac disease defined as following: A malabsorption syndrome that is precipitated by the ingestion of foods containing GLUTEN, such as wheat, rye, and barley. It is characterized by INFLAMMATION of the SMALL INTESTINE, loss of MICROVILLI structure, failed INTESTINAL ABSORPTION, and MALNUTRITION..", "label": "yes"} {"id": "converted_2934", "sentence1": "Have machine learning methods been used to predict the severity of major depressive disorder(MDD)?", "sentence2": "Here, we conduct a meta-review to identify predictors of response to antidepressant therapy in order to select robust input features for machine learning models of treatment response. , machine learning framework involving EEG-based functional connectivity to diagnose major depressive disorder (MDD)., Identification of risk factors of treatment resistance may be useful to guide treatment selection, avoid inefficient trial-and-error, and improve major depressive disorder (MDD) care. We extended the work in predictive modeling of treatment resistant depression (TRD) via partition of the data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) cohort into a training and a testing dataset., persistence and severity of major depressive disorder from baseline self-reports, These results confirm that clinically useful MDD risk-stratification models can be generated from baseline patient self-reports and that ML methods improve on conventional methods in developing such models, Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure., Notably, while the only information provided for training the classifiers was T(1)-weighted scans plus a categorical label (major depressive disorder versus controls), both relevance vector machine and support vector machine 'weighting factors' (used for making predictions) correlated strongly with subjective ratings of illness severity., BACKGROUND\nAlthough variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods., BACKGROUND Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods., BACKGROUND Growing evidence documents the potential of machine learning for developing brain based diagnostic methods for major depressive disorder (MDD)., OBJECTIVE We aimed to integrate neural data and an advanced machine learning technique to predict individual major depressive disorder (MDD) patient severity., Furthermore, machine learning weighting factors may reflect an objective biomarker of major depressive disorder illness severity, based on abnormalities of brain structure., BACKGROUND: Although variation in the long-term course of major depressive disorder (MDD) is not strongly predicted by existing symptom subtype distinctions, recent research suggests that prediction can be improved by using machine learning methods.[SEP]Relations: major depressive disorder has relations: disease_protein with MDM4, disease_protein with MDM4, disease_disease with anxiety disorder, disease_disease with anxiety disorder, disease_protein with DRD4, disease_protein with DRD4, disease_protein with DDC, disease_protein with DDC, disease_protein with PCNT, disease_protein with PCNT. Definitions: antidepressant defined as following: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.. TRD defined as following: One component of the gamma-delta T-cell receptor. Encoded by a locus on chromosome 14. Somatic recombination results in formation of the active gene.. MDD defined as following: Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5).", "label": "yes"} {"id": "converted_2667", "sentence1": "Is transcription of eRNA bidirectional?", "sentence2": "In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs)., Kallikrein-related peptidase 3 (KLK3), which codes for prostate-specific antigen (PSA), is a well-known AR-regulated gene and its upstream enhancers produce bidirectional enhancer RNAs (eRNAs), termed KLK3e., The distal enhancer of the gonadotropin hormone α-subunit gene, chorionic gonadotropin alpha (Cga), is responsible for Cga cell-specific expression in gonadotropes and thyrotropes, and we show here that it encodes two bidirectional nonpolyadenylated RNAs whose levels are increased somewhat by exposure to gonadotropin-releasing hormone but are not necessarily linked to Cga transcriptional activity. , A richer picture has taken shape, integrating transcription of coding genes, enhancer RNAs (eRNAs), and various other noncoding transcriptional events. In this review we give an overview of recent studies detailing the mechanisms of RNA polymerase II (RNA Pol II)-based transcriptional initiation and discuss the ways in which transcriptional direction is established as well as its functional implications., XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bidirectional enhancer RNA (eRNA) production at enhancers, XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bidirectional enhancer RNA (eRNA) production at enhancers., The distal enhancer of the gonadotropin hormone α-subunit gene, chorionic gonadotropin alpha (Cga), is responsible for Cga cell-specific expression in gonadotropes and thyrotropes, and we show here that it encodes two bidirectional nonpolyadenylated RNAs whose levels are increased somewhat by exposure to gonadotropin-releasing hormone but are not necessarily linked to Cga transcriptional activity., Using this approach, we have defined a class of primary transcripts (eRNAs) that are transcribed uni- or bidirectionally from estrogen receptor binding sites (ERBSs) with an average transcription unit length of ∼3-5 kb., XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bidirectional enhancer RNA (eRNA) production at enhancers., We identify 76 enhancer RNAs (eRNAs), 40 canonical lncRNAs, 65 antisense lncRNAs and 35 regions of bidirectional transcription (RBT) that are differentially expressed in response to bacterial lipopolysaccharide (LPS)., XR-seq maps capture transcription-coupled repair at sites of divergent gene promoters and bidirectional enhancer RNA (eRNA) production at enhancers., Instead, communication between promoters and enhancers can be bidirectional with promoters required to activate enhancer transcription., A new paradigm has emerged in recent years characterizing transcription initiation as a bidirectional process encompassing a larger proportion of the genome than previously thought.[SEP]Relations: regulation of antisense RNA transcription has relations: bioprocess_bioprocess with regulation of transcription, DNA-templated, bioprocess_bioprocess with regulation of transcription, DNA-templated, bioprocess_bioprocess with positive regulation of antisense RNA transcription, bioprocess_bioprocess with positive regulation of antisense RNA transcription, bioprocess_bioprocess with negative regulation of antisense RNA transcription, bioprocess_bioprocess with negative regulation of antisense RNA transcription. promoter clearance from RNA polymerase I promoter has relations: bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript, bioprocess_bioprocess with promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript. Definitions: gonadotropin-releasing hormone defined as following: Gonadoliberin-2 (10 aa, ~1 kDa) is encoded by the human GNRH2 gene. This protein is involved in the stimulation of luteinizing hormone and follicle-stimulating hormone secretion.. RNAs defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). sites defined as following: A position in relation to its surroundings.. genome defined as following: Anatomical set of genes in all the chromosomes.. promoters defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. prostate-specific antigen defined as following: Prostate-specific antigen (261 aa, ~29 kDa) is encoded by the human KLK3 gene. This protein plays a role in both proteolysis and seminal fluid liquefaction.. PSA defined as following: A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.. Kallikrein-related peptidase 3 defined as following: Serine proteases that are found in many different tissues and fluids in the body. The kallikrein protease family is comprised of potent vasodilators and hypotensives agents, thus they play important roles in inflammation and blood pressure. These enzymes normally reside in the body as inactive prekallikreins, which are activated by Hageman factor.. enhancer defined as following: A 50-150bp DNA sequence that increases the rate of transcription of coding sequences. It may be located at various distances and in either orientation upstream from, downstream from or within a structural gene. When bound by a specific transcription factor it increases the levels of expression of the gene, but is not sufficient alone to cause expression. Distinguished from a promoter, that is alone sufficient to cause expression of the gene when bound.. RNA polymerase II defined as following: A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC 2.7.7.6.. LPS defined as following: A rare autosomal dominant syndrome caused by mutations in the IRF6 gene. It is characterized by a cleft palate and/or pits on the lower lip. Other signs and symptoms include absent teeth, palate and tongue deformities..", "label": "yes"} {"id": "converted_3695", "sentence1": "Are Chernobyl survivors at increased risk for breast cancer?", "sentence2": "Results: A more aggressive course of breast cancer is observed in patients exposed to radiation from the Chernobyl accident under the age of 30 years (P < .01). , A significant excess of multiple myeloma incidence [standardized incidence rate (SIR) 1.61 %, 95% confidence interval (CI) 1.01-2.21], thyroid cancer (SIR 4.18, 95% CI 3.76-4.59), female breast cancer (SIR 1.57 CI 1.40-1.73), and all cancers combined (SIR 1.07; 95% CI 1.05-1.09) was registered. , Possible effects for further study include increased rates of thyroid, breast, and lung cancers and multiple myeloma; reduction of radiation risks of leukemia to population levels; and increased morbidity and mortality of cleanup workers from cardio- and cerebrovascular pathology., Furthermore, the upward trends of increases in a variety of other tumors including breast cancer, cancers of central nervous system and renal cancer have been reported in the persons exposed to Chornobyl fallout., Epidemiological cohort studies found increased incidence (1990-2012 gg.) of thyroid cancer in victims of Chernobyl accident (liquidators - in 4.6 times, evacuated - in 4.0 times, residents of contaminated areas - in 1.3 times) and increased incidence of breast cancer in female workers of 1986-1987., Historically, data from the Chernobyl reactor accident 27 years ago demonstrated a strong correlation with thyroid cancer, but data on the radiation effects of Chernobyl on breast cancer incidence have remained inconclusive., Re-analyzing the data reveals that the incidence of breast cancer in Chernobyl-disaster-exposed women could be higher than previously thought. , For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. , In contrast, millions of people were exposed to radioactive isotopes in the fallout from the Chernobyl accident, within the first 20 years there was a large increase in thyroid carcinoma incidence and a possible radiation-related increase in breast cancer, but as yet there is no general increase in malignancies. , The study demonstrated increases in breast cancer incidence in all areas following the Chernobyl accident, reflecting improvements in cancer diagnosis and registration., An increase in breast cancer incidence has been reported in areas of Belarus and Ukraine contaminated by the Chernobyl accident and has become an issue of public concern., The study demonstrated increases in breast cancer incidence in all areas following the Chernobyl accident, reflecting improvements in cancer diagnosis and registration.[SEP]Relations: malignant neoplasm of chest wall has relations: disease_disease with thoracic cancer, disease_disease with thoracic cancer, disease_disease with chest wall bone cancer, disease_disease with chest wall bone cancer. Multiple myeloma has relations: disease_phenotype_positive with capillary leak syndrome, disease_phenotype_positive with capillary leak syndrome, drug_effect with Lenalidomide, drug_effect with Lenalidomide. Neoplasm of the thyroid gland has relations: disease_phenotype_positive with familial colorectal cancer, disease_phenotype_positive with familial colorectal cancer. Definitions: leukemia defined as following: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006). breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. lung cancers defined as following: A primary or metastatic malignant neoplasm involving the lung.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. breast defined as following: In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. renal cancer defined as following: Primary or metastatic malignant neoplasm involving the kidney.. thyroid cancer defined as following: A primary or metastatic malignant neoplasm affecting the thyroid gland.. isotopes defined as following: Atomic species differing in mass number but having the same atomic number. (Grant & Hackh's Chemical Dictionary, 5th ed). multiple myeloma defined as following: A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY..", "label": "yes"} {"id": "converted_480", "sentence1": "Are epigenetic modifications implicated in cardiovascular development and disease?", "sentence2": "Gene expression regulation through the interplay of DNA methylation and histone modifications is well-established, although the knowledge about the function of epigenetic signatures in cardiovascular disease is still largely unexplored., The study of epigenetic markers is, therefore, a very promising frontier of science which may aid in a deeper understanding of molecular mechanisms underlying the modulation of gene expression in the biomolecule pathways linked to cardiovascular diseases., This review highlights our current knowledge of epigenetic gene regulation and the evidence that chromatin remodeling and histone modifications play key roles in the pathogenesis of cardiovascular disease through (re)programming of cardiovascular (stem) cells commitment, identity and function., Notably, multiple subunits of switching defective/sucrose non-fermenting (SWI/SNF) chromatin-remodeling complexes have been identified as strong candidates underlying these defects because they physically and functionally interact with cardiogenic transcription factors critical to cardiac development, such as TBX5, GATA-4, and NKX2-5. While these studies indicate a critical role of SWI/SNF complexes in cardiac development and congenital heart disease, many exciting new discoveries have identified their critical role in the adult heart in both physiological and pathological conditions involving multiple cell types in the heart, including cardiomyocytes, vascular endothelial cells, pericytes, and neural crest cells., Recent studies have greatly expanded our understanding of the regulation of cardiovascular development at the chromatin level, including the remodeling of chromatin and the modification of histones. Chromatin-level regulation integrates multiple inputs and coordinates broad gene expression programs. Thus, understanding chromatin-level regulation will allow for a better appreciation of gene regulation as a whole and may set a fundamental basis for cardiovascular disease., Genetic and epigenetic factors are of great importance in cardiovascular biology and disease. Tobacco-smoking, one of the most important cardiovascular risk factors, is itself partially determined by genetic background and is associated with altered epigenetic patterns., Epigenetic modifications, including DNA methylation, histone modification (acetylation, methylation and phosphorylation) and miRNA, are critical for regulating developmental events. However, aberrant epigenetic mechanisms may lead to pathological consequences such as cardiovascular disease (CAD), neurodegenerative disease, obesity, metabolic disorder, bone and skeletal diseases and various cancers., Cardiovascular disease pathways are now being approached from the epigenetic perspective, including those associated with atherosclerosis, angiogenesis, ischemia-reperfusion damage, and the cardiovascular response to hypoxia and shear stress, among many others. With increasing interest and expanding partnerships in the field, we can expect new insights to emerge from epigenetic perspectives of cardiovascular health., Epigenetic modifications are heritable alterations of the genome, which can govern gene expression without altering the DNA sequence. The purpose of this review is to render an overview of the possible mechanisms of epigenetic regulation of gene expression in response to environmental pollutants leading to cardiovascular diseases (CVD)., From varied study approaches directed either toward the general understanding of the key pathway regulatory genes, or sampling population cohorts for global and gene-specific changes, it has been possible to identify several epigenetic signatures of environmental exposure relevant to CVD., An understanding of chromatin remodelling in response to environmental stimuli conducive to CVD is emerging, with the promise of novel diagnostic and therapeutic candidates., Consolidated knowledge is accumulating as to the role of epigenetic regulatory mechanisms in the physiology of vascular development and vascular tone as well as in the pathogenesis of cardiovascular disease. The modulation of gene expression through modification of the epigenome by structural changes of the chromatin architecture without alterations of the associated genomic DNA sequence is part of the cellular response to environmental changes. Such environmental conditions, which are finally being translated into adaptations of the cardiovascular system, also comprise pathological conditions such as atherosclerosis or myocardial infarction. , Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease. Histone modifications lead to the modulation of the expression of genetic information through modification of DNA accessibility. In addition, RNA-based mechanisms (e.g., microRNAs and long non-coding RNAs) influence the development of disease., We here outline the recent work pertaining to epigenetic changes in a cardiovascular disease setting., Epigenetics may represent one of the possible scientific explanations of the impact of such intrauterine risk factors for the subsequent development of cardiovascular disease (CVD) during adulthood., Epigenetic mechanisms include DNA methylation, histone modification, and microRNA alterations, which collectively enable the cell to respond quickly to environmental changes. A number of CVD risk factors, such as nutrition, smoking, pollution, stress, and the circadian rhythm, have been associated with modification of epigenetic marks. Further examination of these mechanisms may lead to earlier prevention and novel therapy for CVD., Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease., Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease., Epigenetic alterations are associated with inflammation and cardiovascular disease in patients with chronic kidney disease., Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease, Epigenetic mechanisms that underpin metabolic and cardiovascular diseases., Epigenetic regulation of cardiovascular differentiation., Epigenetic control mechanisms play a key role in the regulation of embryonic development and tissue homeostasis and modulate cardiovascular diseases.[SEP]Relations: cardiovascular disease has relations: disease_disease with autoimmune disease of cardiovascular system, disease_disease with autoimmune disease of cardiovascular system, contraindication with Epinephrine, contraindication with Epinephrine, contraindication with Ephedrine, contraindication with Ephedrine, disease_disease with disease by anatomical system, disease_disease with disease by anatomical system, disease_disease with congenital anomaly of cardiovascular system, disease_disease with congenital anomaly of cardiovascular system. Definitions: DNA sequence defined as following: The sequence of nucleotide residues along a DNA chain.. atherosclerosis defined as following: Thickening and loss of elasticity of the walls of ARTERIES of all sizes. There are many forms classified by the types of lesions and arteries involved, such as ATHEROSCLEROSIS with fatty lesions in the ARTERIAL INTIMA of medium and large muscular arteries.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. cardiomyocytes defined as following: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).. cardiovascular defined as following: The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body.. histones defined as following: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. chronic kidney disease defined as following: Impairment of the renal function secondary to chronic kidney damage persisting for three or more months.. Genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. histone modification defined as following: The covalent alteration of one or more amino acid residues within a histone protein. [GOC:krc]. cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. hypoxia defined as following: A disorder characterized by a decrease in the level of oxygen in the body.. TBX5 defined as following: This gene is involved in transcriptional regulation and mesoderm differentiation.. NKX2-5 defined as following: This gene plays a role in both transcriptional regulation and heart development.. pericytes defined as following: Unique slender cells with multiple processes extending along the capillary vessel axis and encircling the vascular wall, also called mural cells. Pericytes are imbedded in the BASEMENT MEMBRANE shared with the ENDOTHELIAL CELLS of the vessel. Pericytes are important in maintaining vessel integrity, angiogenesis, and vascular remodeling.. neurodegenerative disease defined as following: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.. metabolic disorder defined as following: Generic term for diseases caused by an abnormal metabolic process. It can be congenital due to inherited enzyme abnormality (METABOLISM, INBORN ERRORS) or acquired due to disease of an endocrine organ or failure of a metabolically important organ such as the liver. (Stedman, 26th ed). microRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. modification defined as following:Respond with exceptions, completions and modifications or revisions done before completion
. neural crest cells defined as following: Neuroectodermal cells of the neural crest. They differentiate into various cell types during EMBRYOGENESIS including craniofacial MESENCHYME; ENDOCRINE CELLS; MELANOCYTES and PERIPHERAL NERVOUS SYSTEM.. genome defined as following: Anatomical set of genes in all the chromosomes.. CVD defined as following: A spectrum of pathological conditions of impaired blood flow in the brain. They can involve vessels (ARTERIES or VEINS) in the CEREBRUM, the CEREBELLUM, and the BRAIN STEM. Major categories include INTRACRANIAL ARTERIOVENOUS MALFORMATIONS; BRAIN ISCHEMIA; CEREBRAL HEMORRHAGE; and others.. congenital heart disease defined as following: Developmental abnormalities involving structures of the heart. These defects are present at birth but may be discovered later in life..", "label": "yes"} {"id": "converted_2130", "sentence1": "Have studies shown that there is no link between DNA methylation patterns and Post Traumatic Stress Disorder?", "sentence2": "Using pre-deployment SKA2 methylation levels and childhood trauma exposure, we found that the previously published suicide prediction rule significantly predicted post-deployment PTSD symptoms (AUC=0.66, 95% CI: 0.53-0.79) with an optimal sensitivity of 0.81 and specificity of 0.91. Permutation analysis using random methylation loci supported these findings. Together, these data establish the importance of SKA2 for cortisol stress responsivity and the development of PTSD and provide further evidence that SKA2 is a promising biomarker for stress-related disorders including PTSD., Results provide novel support for PTSD-related accelerated aging in DNAm and extend the evidence base of known DNAm age correlates to the domains of neural integrity and cognition., We investigated serum DNA methylation patterns in genomic repetitive elements, LINE-1 and Alu, for post-traumatic stress disorder (PTSD) cases and controls who were US military service members recently deployed to Afghanistan or Iraq., In light of its role in glucocorticoid receptor transactivation, we investigated whether SKA2 DNA methylation influences cortisol stress reactivity and is involved in the development of post-traumatic stress disorder (PTSD)., These results suggest that alterations in global methylation pattern are involved in behavioural adaptation to environmental stress and pinpoint Dlgap2 as a possible target in PTSD., Here we examined whether there was a link between an established rat model of post-traumatic stress disorder (PTSD) and Bdnf DNA methylation, We investigated serum DNA methylation patterns in genomic repetitive elements, LINE-1 and Alu, for post-traumatic stress disorder (PTSD) cases and controls who were US military service members recently deployed to Afghanistan or Iraq.Cases (n = 75) had a postdeployment diagnosis of PTSD, DNA methylation in repetitive elements and post-traumatic stress disorder: a case-control study of US military service members, Here we examined whether there was a link between an established rat model of post-traumatic stress disorder (PTSD) and Bdnf DNA methylation. , DNA methylation in repetitive elements and post-traumatic stress disorder: a case-control study of US military service members., AIM: We investigated serum DNA methylation patterns in genomic repetitive elements, LINE-1 and Alu, for post-traumatic stress disorder (PTSD) cases and controls who were US military service members recently deployed to Afghanistan or Iraq. , Together, these results suggest that psychosocial stress may alter global and gene-specific DNA methylation patterns potentially associated with peripheral immune dysregulation., DNA methylation in vulnerability to post-traumatic stress in rats: evidence for the role of the post-synaptic density protein Dlgap2., Subjects with PTSD showed a higher DNA methylation of four CpG sites at the BDNF promoter compared with those without PTSD, Cumulatively, the data suggest that epigenetic variation at SKA2 mediates vulnerability to suicidal behaviors and PTSD through dysregulation of the HPA axis in response to stress.[SEP]Relations: post-traumatic stress disorder has relations: disease_disease with neurotic disorder, disease_disease with neurotic disorder. DLGAP2 has relations: anatomy_protein_absent with decidua, anatomy_protein_absent with decidua, anatomy_protein_present with hypothalamus, anatomy_protein_present with hypothalamus, anatomy_protein_present with substantia nigra, anatomy_protein_present with substantia nigra, anatomy_protein_present with prefrontal cortex, anatomy_protein_present with prefrontal cortex. Definitions: trauma defined as following: Damage inflicted on the body as the direct or indirect result of an external force, with or without disruption of structural continuity.. SKA2 defined as following: This gene plays a role in microtubule binding and chromosome segregation.. post-traumatic stress disorder defined as following: A class of traumatic stress disorders with symptoms that last more than one month.. LINE-1 defined as following: A long interspersed element (LINE) found in mammals. The LINE-1 element is the only active LINE in humans and is approximately 6,000 base pairs long. This nucleotide sequence consists of two non-overlapping open reading frames (ORF) flanked by a 5' untranslated region (UTR), which contains a strong RNA polymerase II promoter sequence, and target side duplications. The first ORF encodes a 500 amino acid, ~40 kDa leucine zipper-containing RNA-binding protein. The second ORF encodes an ~150 kDa protein that has endonuclease and reverse transcriptase activity. Increased LINE-1 copy number is associated with cancer and neuropathy.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. glucocorticoid receptor defined as following: Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example.. HPA defined as following: interaction and feedback in stimulation or suppression of hormones produced in the hypothalamus, pituitary, and adrenal glands..", "label": "no"} {"id": "converted_682", "sentence1": "Is sumoylation implicated in myogenesis?", "sentence2": "Sentrin/small ubiquitin-like modifier (SUMO)-specific protease 2 (SENP2) has broad de-SUMOylation activities in vitro, which is essential for embryonic heart development., Silencing SENP2 can reduce myostatin expression and, therefore, promote myogenesis of skeletal muscle. These results reveal the important role of SENP2 in the regulation of myostatin expression and myogenesis., Overexpression of c-Ski/SnoN also induces skeletal muscle differentiation, but how c-Ski/SnoN function in myogenesis is largely unknown., Notably, loss of sumoylation in the Lys-50 site (via a Lys-to-Arg point mutation) potently activates muscle-specific gene expression and enhances myotube formation. Our study suggests a novel role for SUMO modification in the regulation of myogenic differentiation., Although this modification has little effect on SnoN repression of the plasminogen activator inhibitor-1 promoter and only modestly potentiates SnoN repression of the p21 promoter, SnoN sumoylation robustly augments the ability of SnoN to suppress transcription of the myogenesis master regulatory gene myogenin, Our study also points to a physiological role for SnoN sumoylation in the control of myogenin expression in differentiating muscle cells., Here, we biochemically characterize SnoN sumoylation in detail and report the physiological function of the modification. , An essential role of small ubiquitin-like modifier (SUMO)-specific Protease 2 in myostatin expression and myogenesis., These results reveal the important role of SENP2 in the regulation of myostatin expression and myogenesis., The E3 SUMO ligase Nse2 regulates sumoylation and nuclear-to-cytoplasmic translocation of skNAC-Smyd1 in myogenesis., Sumoylation of the basic helix-loop-helix transcription factor sharp-1 regulates recruitment of the histone methyltransferase G9a and function in myogenesis., We show that the overall load of sumoylated proteins present in myoblasts diminishes progressively throughout myogenesis, These novel results suggest that protein sumoylation plays a pivotal role in myoblast differentiation and is required to regulate the activity of key targets downstream of MyoD and myogenin., a composite sequence motif has recently been identified that couples phosphorylation, sumoylation, and perhaps also deacetylation to control transcriptional repression in stress response, mitogen and nuclear hormone signaling, myogenesis, and neuronal differentiation., Mutation of these SUMO acceptor sites in Sharp-1 does not impact its subcellular localization but attenuates its ability to act as a transcriptional repressor and inhibit myogenic differentiation. Consistently, co-expression of the SUMO protease SENP1 with wild type Sharp-1 abrogates Sharp-1-dependent inhibition of myogenesis. , Transforming growth factor-beta-independent regulation of myogenesis by SnoN sumoylation., Ubiquitin Specific Protease 25 (USP25), a member of the deubiquitinase family, is involved in several disease-related signal pathways including myogenesis, immunity and protein degradation. , In addition, we show that the skNAC interaction partner Smyd1 contains a putative sumoylation motif and is sumoylated in muscle cells, with depletion of Mms21/Nse2 leading to reduced concentrations of sumoylated Smyd1. Taken together, our data suggest that the function, specifically the balance between the nuclear and cytosolic roles, of the skNAC-Smyd1 complex might be regulated by sumoylation.[SEP]Relations: EHMT2 has relations: pathway_protein with Regulation of TP53 Activity through Methylation, pathway_protein with Regulation of TP53 Activity through Methylation, bioprocess_protein with regulation of histone H3-K4 methylation, bioprocess_protein with regulation of histone H3-K4 methylation, bioprocess_protein with regulation of histone H3-K9 methylation, bioprocess_protein with regulation of histone H3-K9 methylation. histone methyltransferase complex has relations: cellcomp_protein with PRDM4, cellcomp_protein with PRDM4. BHLHE41 has relations: bioprocess_protein with regulation of neurogenesis, bioprocess_protein with regulation of neurogenesis. Definitions: myostatin defined as following: A growth differentiation factor that is a potent inhibitor of SKELETAL MUSCLE growth. It may play a role in the regulation of MYOGENESIS and in muscle maintenance during adulthood.. muscle cells defined as following: Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal (MUSCLE FIBERS, SKELETAL), cardiac (MYOCYTES, CARDIAC), and smooth (MYOCYTES, SMOOTH MUSCLE). They are derived from embryonic (precursor) muscle cells called MYOBLASTS.. skNAC defined as following: Human NACA wild-type allele is located within 12q23-q24.1 and is approximately 25 kb in length. This allele, which encodes nascent polypeptide-associated complex subunit alpha protein, is involved in the regulation of protein sorting. A point mutation in the gene may be associated with ovarian serous carcinoma.. SnoN defined as following: Ski-like protein (684 aa, ~77 kDa) is encoded by the human SKIL gene. This protein plays a role in the regulation of both gene transcription and signal transduction.. histone methyltransferase defined as following: Enzymes that catalyze the transfer of methyl groups to LYSINE or ARGININE residues of HISTONES, especially histone H3 and histone H4 proteins. They play a critical role in EPIGENETIC PROCESSES.. transcriptional repressor defined as following: Transcription Repressor/Corepressor Gene encodes Transcriptional Repressor/Corepressor, proteins that can regulate transcription by binding to the operator and causing repression. (from Glick: Glossary of Biochemistry and Molecular Biology). MyoD defined as following: Human MYOD1 wild-type allele is located in the vicinity of 11p15.4 and is approximately 3 kb in length. This allele, which encodes myoblast determination protein 1, is involved in the regulation of transcription, the cell cycle and the mediation of muscle differentiation.. myogenin defined as following: Myogenin (224 aa, ~25 kDa) is encoded by the human MYOG gene. This protein is involved in both transcription and myogenesis.. SENP2 defined as following: Human SUMO1 wild-type allele is located in the vicinity of 2q33 and is approximately 32 kb in length. This allele, which encodes small ubiquitin-related modifier 1 protein, is involved in the post-translational modification of proteins.. myoblasts defined as following: Embryonic (precursor) cells of the myogenic lineage that develop from the MESODERM. They undergo proliferation, migrate to their various sites, and then differentiate into the appropriate form of myocytes (MYOCYTES, SKELETAL; MYOCYTES, CARDIAC; MYOCYTES, SMOOTH MUSCLE).. mitogen defined as following: Growth Factors are extracellular signaling molecules (ligands) involved in control of target cell proliferation, cell survival, and cell differentiation. (NCI). modification defined as following:Respond with exceptions, completions and modifications or revisions done before completion
. Mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. p21 defined as following: A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.. regulatory gene defined as following: Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions..", "label": "yes"} {"id": "converted_298", "sentence1": "Can a given genotype exhibit opposite fitness effects (beneficial and detrimental) within the same environment?", "sentence2": "Mutations beneficial in one environment may cause costs in different environments, resulting in antagonistic pleiotropy. Here, we describe a novel form of antagonistic pleiotropy that operates even within the same environment, where benefits and deleterious effects exhibit themselves at different growth rates., The hfq mutations were beneficial, deleterious or neutral at an intermediate growth rate (0.5 h(-1)) and one changed from beneficial to deleterious within a 36 min difference in doubling time., Two genetic models exist to explain the evolution of ageing - mutation accumulation (MA) and antagonistic pleiotropy (AP)., Under AP, late-acting deleterious mutations accumulate because they confer beneficial effects early in life., Many marker loci responded in opposite directions to selection for late- and early-life fitness, indicating negative genetic correlations or trade-offs between those traits. Indirect evidence suggested that some negative genetic correlations were due to antagonistic pleiotropy., Here, we describe a novel form of antagonistic pleiotropy that operates even within the same environment, where benefits and deleterious effects exhibit themselves at different growth rates., The basis of antagonistic pleiotropy in hfq mutations that have opposite effects on fitness at slow and fast growth rates., Here, we describe a novel form of antagonistic pleiotropy that operates even within the same environment, where benefits and deleterious effects exhibit themselves at different growth rates[SEP]Relations: adaptation to pheromone regulating conjugation with mutual genetic exchange has relations: bioprocess_bioprocess with negative adaptation of signaling pathway, bioprocess_bioprocess with negative adaptation of signaling pathway, bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange. migraine with or without aura, susceptibility to has relations: disease_phenotype_positive with Photophobia, disease_phenotype_positive with Photophobia, disease_phenotype_positive with Hemiparesis, disease_phenotype_positive with Hemiparesis. Lacrimation abnormality has relations: disease_phenotype_positive with EEC syndrome, disease_phenotype_positive with EEC syndrome. Definitions: Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. genotype defined as following: The determination of the DNA sequence of an individual..", "label": "yes"} {"id": "converted_3327", "sentence1": "Does Uc.63+ promote sensitivity to treatment in prostate cancer?", "sentence2": "Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer., The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis including prostate cancer (PC). In this study, we investigated the transcriptional levels of 26 representative T-UCRs and determined the regions that were differentially expressed in PC. Quantitative real-time polymerase chain reaction analysis revealed that the expression of T-UCR Uc.63+ was increased in PC tissues. MTT assay and wound healing assay revealed that Uc.63+ was involved in cell growth and cell migration. miR-130b was predicted to have binding sites within the Uc.63+ sequence. The expression of miR-130b was significantly disturbed by the overexpression or knockdown of Uc.63+. We also showed that Uc.63+ regulated the expression of MMP2 via miR-130b regulation. Furthermore, overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation. In patients treated with docetaxel, the expression of serum Uc.63+ in the docetaxel-resistant patients was higher than that in the docetaxel-sensitive patients (P = 0.011). Moreover, Kaplan-Meier analysis showed that the high expression of serum Uc.63+ correlated with a worse prognosis (P = 0.020). These results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC., Transcribed ultraconserved region Uc.63+ promotes resistance to docetaxel through regulation of androgen receptor signaling in prostate cancer, These results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC, Furthermore , overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation, These results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC., Furthermore, overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation., These results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC.[SEP]Relations: benign neoplasm of prostate has relations: disease_disease with prostate leiomyoma, disease_disease with prostate leiomyoma, disease_disease with fibroma of prostate, disease_disease with fibroma of prostate, disease_disease with prostatic adenoma, disease_disease with prostatic adenoma, disease_disease with prostate neoplasm, disease_disease with prostate neoplasm, disease_disease with benign prostate phyllodes tumor, disease_disease with benign prostate phyllodes tumor. Definitions: MMP2 defined as following: 72 kDa type IV collagenase (660 aa, ~74 kDa) is encoded by the human MMP2 gene. This protein is involved in both proteolysis and angiogenesis.. prostate cancer defined as following: A primary or metastatic malignant tumor involving the prostate gland. The vast majority are carcinomas.. binding sites defined as following: The parts of a macromolecule that directly participate in its specific combination with another molecule.. AR defined as following: Aldose reductase (316 aa, ~36 kDa) is encoded by the human AKR1B1 gene. This protein plays a role in glucose metabolism.. PC defined as following: A group of inherited ectodermal dysplasias whose most prominent clinical feature is hypertrophic nail dystrophy resulting in PACHYONYCHIA. Several specific subtypes of pachyonychia congenita have been associated with mutations in genes that encode KERATINS.. docetaxel defined as following: A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER..", "label": "no"} {"id": "converted_1623", "sentence1": "Is the Histidine-Rich Calcium Binding protein (HRC) related to arrhythmias and cardiac disease?", "sentence2": "A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR) histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy. , These findings suggest that aberrant SR Ca2+ release and increased susceptibility to delayed afterdepolarizations underlie triggered arrhythmic activity in human Ala96 HRC carriers., The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers., These findings indicate that the HRC Ser96Ala variant increases the propensity of arrhythmogenic Ca(2+) waves in the stressed failing heart, suggesting a link between this genetic variant and life-threatening ventricular arrhythmias in human carriers., HRC plays an important role in myocyte differentiation and in antiapoptotic cardioprotection against ischemia/reperfusion induced cardiac injury. Interestingly, HRC has been linked with familiar cardiac conduction disease and an HRC polymorphism was shown to associate with malignant ventricular arrhythmias in the background of idiopathic dilated cardiomyopathy., This review summarizes studies, which have established the critical role of HRC in Ca(2+)-homeostasis, suggesting its importance in cardiac physiology and pathophysiology., HRC is a SR luminal Ca(2+) binding protein known to associate with both triadin and the sarcoplasmic reticulum Ca(2+)-ATPase, and may thus mediate the crosstalk between SR Ca(2+) uptake and release. Indeed, evidence from genetic models of JCN and HRC indicate that they are important in cardiophysiology as alterations in these proteins affect SR Ca(2+) handling and cardiac function. In addition, downregulation of JCN and HRC may contribute to Ca(2+) cycling perturbations manifest in the failing heart, where their protein levels are significantly reduced., The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM., AAV-mediated knock-down of HRC exacerbates transverse aorta constriction-induced heart failure., Chronic overexpression of HRC that may disrupt intracellular Ca(2+) homeostasis is implicated in pathogenesis of cardiac hypertrophy, Ablation of HRC showed relatively normal phenotypes under basal condition, but exhibited a significantly increased susceptibility to isoproterenol-induced cardiac hypertrophy, Our results present evidence that down-regulation of HRC could deteriorate cardiac function in TAC-FH through perturbed SR-mediated Ca(2+) cycling, However, AAV9-mediated HRC-KD in TAC-FH was associated with decreased fractional shortening and increased cardiac fibrosis compared with control., Histidine-rich calcium binding protein (HRC) is a high capacity, low affinity Ca(2+) binding protein, specifically expressed in striated muscles of mammals. In rabbit skeletal and cardiac muscles, HRC binds to sarcoplasmic reticulum (SR) membranes via triadin, a junctional SR protein. Recently, a potential role in heart failure and arrhythmogenesis has been assigned to HRC due to its activity as regulator of SR Ca(2+) uptake and Ca(2+) release., In addition, HRC null mice displayed a significantly exaggerated response to the induction of cardiac hypertrophy by isoproterenol compared to their wild-type littermates. The exaggerated response of HRC knockout mice to the induction of cardiac hypertrophy is consistent with a regulatory role for HRCBP in calcium handling in vivo and suggests that mutations in HRC, in combination with other genetic or environmental factors, might contribute to pathological hypertrophy and heart failure., We observed that the levels of HRC were reduced in animal models and human heart failure., Collectively, these data indicate that alterations in expression levels of HRC are associated with impaired cardiac SR Ca homeostasis and contractile function., Abnormal calcium cycling and cardiac arrhythmias associated with the human Ser96Ala genetic variant of histidine-rich calcium-binding protein., The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy., Interestingly, HRC has been linked with familiar cardiac conduction disease and an HRC polymorphism was shown to associate with malignant ventricular arrhythmias in the background of idiopathic dilated cardiomyopathy[SEP]Relations: myocardium has relations: anatomy_protein_present with HRC, anatomy_protein_present with HRC, anatomy_protein_present with HRAS, anatomy_protein_present with HRAS, anatomy_protein_present with MRC1, anatomy_protein_present with MRC1. Arrhythmia has relations: disease_phenotype_positive with HEC syndrome, disease_phenotype_positive with HEC syndrome, disease_phenotype_positive with mitochondrial trifunctional protein deficiency, disease_phenotype_positive with mitochondrial trifunctional protein deficiency. Definitions: calcium defined as following: A dietary supplement containing the mineral calcium.. variant defined as following: An alteration or difference from a norm or standard.. ventricular arrhythmias defined as following: A disorder characterized by an electrocardiographic finding of an atypical cardiac rhythm resulting from a pathologic process in the cardiac ventricles.. heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. cardiac arrhythmias defined as following: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. sudden death defined as following: The abrupt cessation of all vital bodily functions, manifested by the permanent loss of total cerebral, respiratory, and cardiovascular functions.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. isoproterenol defined as following: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.. sarcoplasmic reticulum defined as following: A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.. dilated cardiomyopathy defined as following: Cardiomyopathy which is characterized by dilation and contractile dysfunction of the left and right ventricles. It may be idiopathic, or it may result from a myocardial infarction, myocardial infection, or alcohol abuse. It is a cause of congestive heart failure.. SR defined as following: Human SNCG wild-type allele is located within10q23.2-q23.3 and is approximately 13 kb in length. This allele, which encodes gamma-synuclein protein, plays a role in the modulation of axonal architecture and neurofilament integrity. This gene is highly expessed in advanced breast carcinomas, suggesting a correlation between SNCG overexpression and breast tumor development.. sarcoplasmic reticulum Ca(2+)-ATPase defined as following: Calcium-transporting ATPases that catalyze the active transport of CALCIUM into the SARCOPLASMIC RETICULUM vesicles from the CYTOPLASM. They are primarily found in MUSCLE CELLS and play a role in the relaxation of MUSCLES.. cardiac hypertrophy defined as following: Enlargement of the HEART due to chamber HYPERTROPHY, an increase in wall thickness without an increase in the number of cells (MYOCYTES, CARDIAC). It is the result of increase in myocyte size, mitochondrial and myofibrillar mass, as well as changes in extracellular matrix.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. DCM defined as following: A chlorinated methotrexate derivative. Dichloromethotrexate inhibits the enzyme dihydrofolate reductase, thereby preventing the synthesis of purine nucleotides and thymidylates and inhibiting DNA and RNA synthesis. This agent is metabolized and excreted by the liver. (NCI04). cardiac muscles defined as following: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.. myocyte defined as following: Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal (MUSCLE FIBERS, SKELETAL), cardiac (MYOCYTES, CARDIAC), and smooth (MYOCYTES, SMOOTH MUSCLE). They are derived from embryonic (precursor) muscle cells called MYOBLASTS.. mammals defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. human defined as following: Members of the species Homo sapiens.. transverse aorta defined as following: The curved section of the aorta between the ascending and the descending tracts. The brachiocephalic, left common carotid and left subclavian arteries branch from the aorta at this section.. polymorphism defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.. cardiac disease defined as following: Pathological conditions involving the HEART including its structural and functional abnormalities.. arrhythmias defined as following: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction..", "label": "yes"} {"id": "converted_2379", "sentence1": "Are loop domains preserved upon cohesin loss?", "sentence2": "Cohesin Loss Eliminates All Loop Domains., The human genome folds to create thousands of intervals, called \"contact domains,\" that exhibit enhanced contact frequency within themselves. \"Loop domains\" form because of tethering between two loci-almost always bound by CTCF and cohesin-lying on the same chromosome. \"Compartment domains\" form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes., cohesin loss eliminates all loop domains[SEP]Relations: Protein S human has relations: drug_drug with Ardeparin, drug_drug with Ardeparin, drug_drug with Parnaparin, drug_drug with Parnaparin, drug_drug with Semuloparin, drug_drug with Semuloparin, drug_drug with Bemiparin, drug_drug with Bemiparin, drug_drug with Biochanin A, drug_drug with Biochanin A. Definitions: CTCF defined as following: CCN family member 2 (349 aa, ~38kDa) is encoded by the human CCN2 gene. This protein plays a role in the promotion of proliferation and differentiation of chondrocytes and also mediates heparin- and divalent cation-dependent cell adhesion in many different cell types..", "label": "no"} {"id": "converted_903", "sentence1": "Does Rad9 interact with Aft1 in S.cerevisiae?", "sentence2": "Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae., Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ∼2% of the coding genome in the absence of exogenously induced DNA damage. Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events., Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast, Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae, Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ?2% of the coding genome in the absence of exogenously induced DNA damage. , Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events.[SEP]Relations: centromere clustering has relations: bioprocess_bioprocess with chromosome localization, bioprocess_bioprocess with chromosome localization, bioprocess_bioprocess with centromere clustering at the mitotic interphase nuclear envelope, bioprocess_bioprocess with centromere clustering at the mitotic interphase nuclear envelope, bioprocess_bioprocess with centromere localization, bioprocess_bioprocess with centromere localization, bioprocess_bioprocess with meiotic centromere clustering, bioprocess_bioprocess with meiotic centromere clustering. anatomical entity has relations: anatomy_anatomy with insect mouthpart, anatomy_anatomy with insect mouthpart. Definitions: centromeres defined as following: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.. genome defined as following: Anatomical set of genes in all the chromosomes.. Rad9 defined as following: Human RAD9A wild-type allele is located within 11q13.1-q13.2 and is approximately 7 kb in length. This allele, which encodes cell cycle checkpoint control protein RAD9A, is involved in the regulation of both DNA repair and cell cycle progression.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine)..", "label": "yes"} {"id": "converted_2571", "sentence1": "Can gas vesicles be detected by ultrasound?", "sentence2": "Gas vesicles-genetically encoded protein nanostructures isolated from buoyant photosynthetic microbes-have recently been identified as nanoscale reporters for ultrasound., Here, we demonstrate that genetic engineering of gas vesicles results in nanostructures with new mechanical, acoustic, surface, and functional properties to enable harmonic, multiplexed, and multimodal ultrasound imaging as well as cell-specific molecular targeting. [SEP]Relations: cell surface has relations: cellcomp_protein with VASN, cellcomp_protein with VASN, cellcomp_protein with CTSZ, cellcomp_protein with CTSZ, cellcomp_protein with VWDE, cellcomp_protein with VWDE, cellcomp_protein with VEGFA, cellcomp_protein with VEGFA, cellcomp_protein with EPCAM, cellcomp_protein with EPCAM. Definitions: surface defined as following: The extended two-dimensional outer boundary of a three-dimensional object..", "label": "yes"} {"id": "converted_3457", "sentence1": "Is Rad4/XPC a DNA damage sensing protein?", "sentence2": "Twist-open mechanism of DNA damage recognition by the Rad4/XPC nucleotide excision repair complex., Kinetic gating mechanism of DNA damage recognition by Rad4/XPC., These findings indicate that the lesions recognized by Rad4/XPC thermodynamically destabilize the Watson-Crick double helix in a manner that facilitates the flipping-out of two base pairs.[SEP]Relations: nerve lesion has relations: disease_disease with ulnar nerve lesion, disease_disease with ulnar nerve lesion, disease_disease with brachial plexus neuritis, disease_disease with brachial plexus neuritis, disease_disease with lesion of sciatic nerve, disease_disease with lesion of sciatic nerve, disease_disease with radial neuropathy, disease_disease with radial neuropathy, disease_disease with femoral neuropathy, disease_disease with femoral neuropathy. Definitions: base pairs defined as following: Pairing of purine and pyrimidine bases by HYDROGEN BONDING in double-stranded DNA or RNA.. lesions defined as following: A localized pathological or traumatic structural change, damage, deformity, or discontinuity of tissue, organ, or body part..", "label": "yes"} {"id": "converted_3683", "sentence1": "Is there an increased risk for meningiomas in childhood leukemia survivors?", "sentence2": "Cranial radiotherapy improves survival of the most common childhood cancers, including brain tumors and leukemia. Unfortunately, long-term survivors are faced with consequences of secondary neoplasia, including radiation-induced meningiomas (RIMs). , Combined chemotherapy and prophylactic cranial irradiation has improved the prognosis of children with acute leukemia. However cranial irradiation carries a latent risk of the induction of secondary intracranial tumors. We encountered a patient who developed multiple intracranial radiation-induced meningiomas (RIMs) 25 years after prophylactic cranial irradiation for the treatment of acute leukemia in childhood. , Focal cranial hyperostosis from meningioma: a complication from previous radiation treatment for childhood T-cell acute lymphoblastic leukemia., Presented is a case of a 20 year man with a history of T-cell lymphoblastic leukemia diagnosed at age 22 months, treated with chemotherapy and cranial irradiation. He had developed increasing prominence of the top of his head over several months. Plain radiograph showed frontal calvarium thickening with focal \"hair-on-end\" periosteal reaction. Magnetic resonance imaging revealed an enhancing dural-based mass with transcalvarial extension, confirmed after resection to be meningioma (World Health Organization Grade I). , RESULTS: Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). , Radiation-induced World Health Organization grade II meningiomas in young patients following prophylactic cranial irradiation for acute lymphoblastic leukemia in childhood. Three case reports., Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia (ALL), but have resulted in an increased risk of late central nervous system tumors, most commonly meningioma, particularly in patients who have received cranial irradiation. , RESULTS: Fifty-nine MRI abnormalities (32 cavernomas, nine focal areas of gliosis, seven dystrophic mineralizations, five cerebral atrophies, four pituitary atrophies, one diffuse radiation leukoencephalopathy, and one meningioma) were found in 43 patients. , Intraventricular meningioma after cranial irradiation for childhood leukemia., Radiation-induced meningiomas may also have predilection to recur. The authors describe a case of an intraventricular meningioma occurring 23 years after cranial irradiation for childhood acute lymphoblastic leukemia., Cumulative incidence at 30 years after the childhood cancer diagnosis was 20.5% (95% confidence interval [CI] = 19.1% to 21.8%) for all subsequent neoplasms, 7.9% (95% CI = 7.2% to 8.5%) for second malignant neoplasms (excluding nonmelanoma skin cancer), 9.1% (95% CI = 8.1% to 10.1%) for nonmelanoma skin cancer, and 3.1% (95% CI = 2.5% to 3.8%) for meningioma. , Radiation-induced meningiomas: a shadow in the success story of childhood leukemia., Although the cohort is small, it seems probable that the increasing incidence of meningioma will shadow the future of cranially irradiated leukemia survivors., Age at the time of irradiation, gender, or cumulative doses of chemotherapeutic agents showed no significant association with the development of meningiomas., Meningioma Screening With MRI in Childhood Leukemia Survivors Treated With Cranial Radiation., High incidence of meningioma in cranial irradiated survivors of childhood acute lymphoblastic leukemia., Radiation-induced World Health Organization grade II meningiomas in young patients following prophylactic cranial irradiation for acute lymphoblastic leukemia in childhood., Radiation-induced meningioma following prophylactic radiotherapy for acute lymphoblastic leukemia in childhood., Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia ( ALL) , but have resulted in an increased risk of late central nervous system tumors , most commonly meningioma , particularly in patients who have received cranial irradiation, Survivors of childhood ALL treated with high-dose cranial irradiation are at risk both for early radiation injury in radiosensitive organs , such as the lens and pituitary gland , and for the later development of a radiation-induced meningioma, Radiation-induced meningiomas: a shadow in the success story of childhood leukemia, We treated 3 young patients with World Health Organization grade II meningiomas who had previously received cranial irradiation for the treatment of childhood ALL: a cerebellopontine angle tumor in a 19-year-old woman , a petroclival tumor in a 28-year-old man , and a frontal parasagittal tumor in a 19-year-old woman, We treated 3 young patients with World Health Organization grade II meningiomas who had previously received cranial irradiation for the treatment of childhood ALL: a cerebellopontine angle tumor in a 19-year-old woman, a petroclival tumor in a 28-year-old man, and a frontal parasagittal tumor in a 19-year-old woman., Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia (ALL), but have resulted in an increased risk of late central nervous system tumors, most commonly meningioma, particularly in patients who have received cranial irradiation., Current chemotherapeutic regimens have been used to successfully treat many children with acute lymphoblastic leukemia (ALL), but have resulted in an increased risk of late central nervous system tumors, most commonly meningioma, particularly in patients who have received cranial irradiation., Long-term survivors who received radiotherapy for ALL in childhood are at risk for late complications, including radiation-induced meningioma.[SEP]Relations: childhood leukemia has relations: disease_disease with childhood malignant neoplasm, disease_disease with childhood malignant neoplasm, disease_disease with bone marrow cancer, disease_disease with bone marrow cancer, disease_disease with leukemia (disease), disease_disease with leukemia (disease), disease_disease with neonatal leukemia, disease_disease with neonatal leukemia, disease_disease with childhood acute myeloid leukemia, disease_disease with childhood acute myeloid leukemia. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. intracranial tumors defined as following: A benign or malignant neoplasm that arises from or metastasizes to structures within the cranium. This includes meningeal and other tumors that occur in the spaces that surround the brain, and neoplasms of the brain.. Childhood Leukemia defined as following: An acute or chronic leukemia that occurs during childhood.. meningioma defined as following: A grade I, slowly growing meningioma. Only a minority of tumors recur following complete resection.. leukemia defined as following: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006). acute lymphoblastic leukemia defined as following: A type of ALL characterized by elevated levels of B-cell lymphoblasts in the bone marrow and the blood. [NCIT:C8644]. meningiomas defined as following: A relatively common neoplasm of the CENTRAL NERVOUS SYSTEM that arises from arachnoidal cells. The majority are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Meningiomas have a predilection to arise from the parasagittal region, cerebral convexity, sphenoidal ridge, olfactory groove, and SPINAL CANAL. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2056-7). acute leukemia defined as following: A clonal (malignant) hematopoietic disorder with an acute onset, affecting the bone marrow and the peripheral blood. The malignant cells show minimal differentiation and are called blasts, either myeloid blasts (myeloblasts) or lymphoid blasts (lymphoblasts).. AML defined as following: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.. nonmelanoma skin cancer defined as following: A carcinoma that arises from the skin. Representative examples are basal cell carcinoma and squamous cell carcinoma.. brain tumors defined as following: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.. intraventricular meningioma defined as following: A meningioma that affects the ventricles of the brain.. neoplasms defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. malignant neoplasms defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. intracranial radiation-induced meningiomas defined as following: A meningioma that arises within the cranial cavity and results from exposure to radiation.. survivors defined as following: Persons who have experienced a prolonged survival after serious disease or who continue to live with a usually life-threatening condition as well as family members, significant others, or individuals surviving traumatic life events.. head defined as following: A projection on the end of an object. myelodysplastic syndrome defined as following: Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.. cranial irradiation defined as following: The exposure of the head to roentgen rays or other forms of radioactivity for therapeutic or preventive purposes.. organs defined as following: A unique macroscopic (gross) anatomic structure that performs specific functions. It is composed of various tissues. An organ is part of an anatomic system or a body region. Representative examples include the heart, lung, liver, spleen, and uterus.. ALL defined as following: Leukemia with an acute onset, characterized by the presence of lymphoblasts in the bone marrow and the peripheral blood. It includes the acute B lymphoblastic leukemia and acute T lymphoblastic leukemia.. man defined as following: Members of the species Homo sapiens.. focal defined as following: Limited to a specific area.. MDS defined as following: A rare syndrome caused by deletion of genetic material in the short arm of chromosome 17. It is characterized by an abnormally smooth brain with fewer folds and grooves. It results in intellectual disability, developmental delay, seizures, spasticity, hypotonia, and feeding difficulties. Affected individuals have distinctive facial features that include a prominent forehead, midface hypoplasia, small, upturned nose, low-set ears, small jaw, and thick upper lip..", "label": "yes"} {"id": "converted_345", "sentence1": "Are circRNAs associated with diseases and traits?", "sentence2": "Circ2Traits: a comprehensive database for circular RNA potentially associated with disease and traits., Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. Their interaction with disease associated miRNAs indicates that circular RNAs are important for disease regulation., Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated, Emerging evidence indicates that circRNAs might play important roles in atherosclerotic vascular disease risk, neurological disorders, prion diseases and cancer; exhibit aberrant expression in colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC); and serve as diagnostic or predictive biomarkers of some diseases, In this paper we studied the potential association of circular RNAs (circRNA) with human diseases in two different ways. Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated., Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated. For the miRNAs associated with individual diseases, we constructed a network of predicted interactions between the miRNAs and protein coding, long non-coding and circular RNA genes.[SEP]Relations: prion disease has relations: disease_disease with kuru, disease_disease with kuru, disease_protein with PRNP, disease_protein with PRNP. nervous system disorder has relations: disease_disease with neuroendocrine disease, disease_disease with neuroendocrine disease. pancreatic ductal adenocarcinoma has relations: disease_protein with KRAS, disease_protein with KRAS, disease_protein with ADA, disease_protein with ADA. Definitions: circular RNAs defined as following: RNA molecules in which the 3' and 5' ends are covalently joined to form a closed continuous loop. They are resistant to digestion by EXORIBONUCLEASES.. cancer defined as following: A malignant tumor at the original site of growth.. RNAs defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). miRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. pancreatic ductal adenocarcinoma defined as following: An infiltrating adenocarcinoma that arises from the epithelial cells of the pancreas. It affects males more often than females and the patients are usually over 50 years of age. Microscopically it is characterized by the presence of glandular (ductal) differentiation and desmoplastic stroma formation. Signs and symptoms include pain, loss of weight, and jaundice. It grows rapidly and is usually detected after it has metastasized to other anatomic sites. The prognosis is usually poor.. CRC defined as following: The disappearance of all signs of cancer, including the absence of a detectable disease-related genetic abnormality, as determined by techniques such as karyotyping or FISH, in response to treatment.. PDAC defined as following: A rare clinical entity including as main characteristics anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia. Only five cases have been reported so far, two of who were siblings. In the three nonfamilial cases, unilateral pulmonary agenesis and microphthalmia were associated with diaphragmatic hernia and pulmonary vessel agenesis. It has been suggested that two different entities can be distinguished: on one hand, the association of anophthalmia-pulmonary hypoplasia with/without anomalies of the face, heart, spleen and uterus, which may be due to a putative autosomal recessive gene with pleiotropic effects; on the other hand, a sporadic association including pulmonary hypoplasia, anophthalmia, unilateral diaphragmatic defect and agenesis of the pulmonary trunk, which may represent the expression of a developmental field defect. There is evidence that syndromic microphthalmia- is caused by homozygous or compound heterozygous mutation in the STRA6 gene on chromosome 15q24.. prion diseases defined as following: A group of genetic, infectious, or sporadic degenerative human and animal nervous system disorders associated with abnormal PRIONS. These diseases are characterized by conversion of the normal prion protein to an abnormal configuration via a post-translational process. In humans, these conditions generally feature DEMENTIA; ATAXIA; and a fatal outcome. Pathologic features include a spongiform encephalopathy without evidence of inflammation. The older literature occasionally refers to these as unconventional SLOW VIRUS DISEASES. (From Proc Natl Acad Sci USA 1998 Nov 10;95(23):13363-83). neurological disorders defined as following: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.. atherosclerotic vascular disease defined as following: Build-up of fatty material and calcium deposition in the arterial wall resulting in partial or complete occlusion of the arterial lumen.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. circRNAs defined as following: RNA molecules in which the 3' and 5' ends are covalently joined to form a closed continuous loop. They are resistant to digestion by EXORIBONUCLEASES..", "label": "yes"} {"id": "converted_3799", "sentence1": "Can SMAD6 variants cause craniosynostosis?", "sentence2": "SMAD6 variants in craniosynostosis: genotype and phenotype evaluation., Enrichment of heterozygous missense and truncating SMAD6 variants was previously reported in nonsyndromic sagittal and metopic synostosis, and interaction of SMAD6 variants with a common polymorphism nearBMP2 (rs1884302) was proposed to contribute to inconsistent penetrance. We determined the occurrence of SMAD6 variants in all types of craniosynostosis, evaluated the impact of different missense variants on SMAD6 function, and tested independently whether rs1884302 genotype significantly modifies the phenotype.METHODS: We performed resequencing of SMAD6 in 795 unsolved patients with any type of craniosynostosis and genotyped rs1884302 in SMAD6-positive individuals and relatives. We examined the inhibitory activity and stability of SMAD6 missense variants.RESULTS: We found 18 (2.3%) different rare damaging SMAD6 variants, with the highest prevalence in metopic synostosis (5.8%) and an 18.3-fold enrichment of loss-of-function variants comparedwith gnomAD data (P < 10-7). Combined with eight additional variants, ≥20/26 were transmitted from an unaffected parent but rs1884302 genotype did not predict phenotype.CONCLUSION: Pathogenic SMAD6 variants substantially increase the risk of both nonsyndromic and syndromic presentations of craniosynostosis, especially metopic synostosis. Functional analysis is important to evaluate missense variants. Genotyping of rs1884302 is not clinically useful. Mechanisms to explain the remarkable diversity of phenotypes associated with SMAD6 variants remain obscure.[SEP]Relations: craniosynostosis Fontaine type has relations: disease_disease with craniosynostosis, disease_disease with craniosynostosis. Metopic synostosis has relations: disease_phenotype_positive with six2-related frontonasal dysplasia, disease_phenotype_positive with six2-related frontonasal dysplasia, disease_phenotype_positive with neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome due to 9q21 microdeletion, disease_phenotype_positive with neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome due to 9q21 microdeletion, disease_phenotype_positive with cranioectodermal dysplasia, disease_phenotype_positive with cranioectodermal dysplasia, disease_phenotype_positive with neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome due to a point mutation, disease_phenotype_positive with neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome due to a point mutation. Definitions: variants defined as following: An alteration or difference from a norm or standard.. SMAD6 defined as following: Mothers against decapentaplegic homolog 6 (496 aa, ~53 kDa) is encoded by the human SMAD6 gene. This protein is involved in receptor signaling-dependent regulation of gene transcription.. craniosynostosis defined as following: This gene plays a role in regulation of transcription and the inhibition of apoptosis. It is also involved in the control of morphogenesis during embryonic development.. genotype defined as following: The determination of the DNA sequence of an individual.. metopic synostosis defined as following: Premature fusion of the metopic suture. [DDD:awilkie].", "label": "yes"} {"id": "converted_2463", "sentence1": "Can Logic Alignment Free (LAF) be used for bacterial genomes classification?", "sentence2": "LAF: Logic Alignment Free and its application to bacterial genomes classification., In this paper, we present Logic Alignment Free (LAF), a method that combines alignment-free techniques and rule-based classification algorithms in order to assign biological samples to their taxa. This method searches for a minimal subset of k-mers whose relative frequencies are used to build classification models as disjunctive-normal-form logic formulas (if-then rules). We apply LAF successfully to the classification of bacterial genomes to their corresponding taxonomy. In particular, we succeed in obtaining reliable classification at different taxonomic levels by extracting a handful of rules, each one based on the frequency of just few k-mers. State of the art methods to adjust the frequency of k-mers to the character distribution of the underlying genomes have negligible impact on classification performance, suggesting that the signal of each class is strong and that LAF is effective in identifying it., In this paper, we present Logic Alignment Free (LAF), a method that combines alignment-free techniques and rule-based classification algorithms in order to assign biological samples to their taxa., LAF: Logic Alignment Free and its application to bacterial genomes classification.[SEP]Relations: interleukin-1 binding has relations: molfunc_protein with NLRP7, molfunc_protein with NLRP7, molfunc_protein with TRIM16, molfunc_protein with TRIM16, molfunc_protein with HAX1, molfunc_protein with HAX1, molfunc_protein with A2M, molfunc_protein with A2M, molfunc_protein with IL1R1, molfunc_protein with IL1R1. Definitions: LAF defined as following: A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.. bacterial genomes defined as following: The genetic complement of a BACTERIA as represented in its DNA..", "label": "yes"} {"id": "converted_3501", "sentence1": "Do MAIT cells have a role in multiple myeloma?", "sentence2": "hus, MAIT cells are reduced in MM patients, which may contribute to disease in these individuals, and moreover, MAIT cells may represent new immunotherapeutic targets for treatment of MM and other malignancies., Here we have analysed the frequency and function of MAIT cells in multiple myeloma (MM) patients. We show that MAIT cell frequency in blood is reduced compared to healthy adult donors, but comparable to elderly healthy control donors, Newly diagnosed MM patient MAIT cells had reduced IFNγ production and CD27 expression, suggesting an exhausted phenotype, although IFNγ-producing capacity is restored in relapsed/refractory patient samples. , We describe recent observations with regard to functional exhaustion of iNKT and MAIT cells in MM pathology and discuss the potential application of checkpoint inhibition as an attractive target for prolonged activation of these immunomodulatory T cells in the treatment of MM., Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma., Thus, MAIT cells are reduced in MM patients, which may contribute to disease in these individuals, and moreover, MAIT cells may represent new immunotherapeutic targets for treatment of MM and other malignancies.[SEP]Relations: Multiple myeloma has relations: disease_phenotype_positive with plasma cell myeloma, disease_phenotype_positive with plasma cell myeloma, drug_effect with Bortezomib, drug_effect with Bortezomib, drug_effect with Muromonab, drug_effect with Muromonab, drug_effect with Lenalidomide, drug_effect with Lenalidomide, drug_effect with Zoledronic acid, drug_effect with Zoledronic acid. Definitions: CD27 defined as following: Human CD27 wild-type allele is located in the vicinity of 12p13 and is approximately 7 kb in length. This allele, which encodes CD27 antigen protein, plays a role in regulating B-cell activation and immunoglobulin synthesis.. multiple myeloma defined as following: A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.. MM defined as following: A unit of concentration (molarity unit) equal to one thousandth of a mole (10E-3 mole) of solute per one liter of solution.. MAIT cell defined as following: A T-cell subtype bearing a semi-invariant T-cell receptor and restricted by the major histocompatibility complex related molecule MR1. These cells occupy peripheral tissues and are noted for their reactivity against various microorganisms of either bacterial or fungal origin.. IFNγ defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous lymphokine interferon gamma (IFN-gamma) with antineoplastic, immunoregulatory, and antiviral activities. Therapeutic IFN-gamma binds to and activates the cell-surface IFN-gamma receptor, stimulating antibody-dependent cytotoxicity and enhances natural killer cell attachment to tumor cells. This agent also activates caspases, thereby inducing apoptosis in malignant cells. (NCI04). disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. malignancies defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas..", "label": "yes"} {"id": "converted_386", "sentence1": "Is pesticide exposure associated with polyneuropathy?", "sentence2": "As the syndrome occurred after the acute cholinergic syndrome but before organophosphate-induced delayed polyneuropathy, the syndrome was called 'intermediate syndrome'., The characteristic features of the IMS are weakness of the muscles of respiration (diaphragm, intercostal muscles and accessory muscles including neck muscles) and of proximal limb muscles. Accompanying features often include weakness of muscles innervated by some cranial nerves. It is now emerging that the degree and extent of muscle weakness may vary following the onset of the IMS. , Electrophysiological studies following OP poisoning have revealed three characteristic phenomena: (i) repetitive firing following a single stimulus; (ii) gradual reduction in twitch height or compound muscle action potential followed by an increase with repetitive stimulation (the 'decrement-increment response'); and (iii) continued reduction in twitch height or compound muscle action potential with repetitive simulation ('decrementing response'). , Organophosphate-induced delayed polyneuropathy is a sensory-motor distal axonopathy which usually occurs after exposure of certain OP insecticides. Neuropathies due to ingestion of OPs have rarely been reported in the literature., We report a patient with serious organophosphorus-induced delayed neuropathy due to malathion injection. The patient was a 32-year-old female who self-injected undetermined amounts of malathion over the median nerve trace on the forearm crease in a suicide attempt which resulted in peripheral neuropathy., Acutely, these patients present with cholinergic crisis; intermediate syndrome and delayed polyneuropathy are other sequel of this form of poisoning., There was no strong evidence of irreversible peripheral nerve damage following acute OP poisoning, however further studies are required., Particular interactions are also addressed, such as those of pesticides acting as endocrine disruptors, the cumulative toxicity of organophosphates and organochlorines resulting in estrogenic effects and the promotion of organophosphate-induced delayed polyneuropathy., The multivariate analyses showed that the population living in areas with high pesticide use had an increased risk for Alzheimer's disease and suicide attempts and that males living in these areas had increased risks for polyneuropathies, affective disorders and suicide attempts. , These compounds cause four important neurotoxic effects in humans: the cholinergic syndrome, the intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP) and chronic organophosphate-induced neuropsychiatric disorder (COPIND). , An 18-year-old woman and a 22-year-old man were admitted to the hospital with weakness, paresthesia, and gait disturbances at 35 and 22 days, respectively, after ingesting dimethyl-2,2-dichloro vinyl phosphate (DDVP). Neurological examination revealed weakness, vibration sense loss, bilateral dropped foot, brisk deep tendon reflexes, and bilaterally positive Babinski sign. Electroneurography demonstrated distal motor polyneuropathy with segmental demyelination associated with axonal degeneration prominent in the distal parts of both lower extremities., Sensory complaints and electrodiagnostic findings consistent with polyneuropathy were found in a minority (3/7) of subjects 28 years after an acute toxic arsenic exposure., Organophosphate-induced delayed polyneuropathy (OPIDP) is a rare toxicity resulting from exposure to certain organophosphorus (OP) esters. , Therefore, OPIDP may develop only after very large exposures to insecticides, causing severe cholinergic toxicity., Several studies have reported the occurrence of sensory neuropathy with exposure to chlorpyrifos and other organophosphorus insecticides, at levels not associated with overt toxicity. , We found no evidence of sensory neuropathy or isolated peripheral abnormalities among subjects with long-term chlorpyrifos exposure at levels known to be associated with the manufacturing process., Persistent, mainly motor, impairment of the peripheral nervous system was found in men two years after OP poisoning, in particular in severe occupational and intentional poisonings with neuropathic OPs. This finding is possibly due to remaining organophosphate induced delayed polyneuropathy., Besides the well known acute cholinergic toxicity, these compounds may cause late-onset distal polyneuropathy occurring two to three weeks after the acute exposure. , Electromyography demonstrated motor weighed sensory-motor polyneuropathy with axonal degeneration significant in the distal parts of bilateral lower extremities. , The two cases are presented here since organophosphate poisonings are common in our country, and since late-onset polyneuropathy is not a well known clinical presentation as acute toxicity., The course of organophosphate-induced delayed polyneuropathy (OPIDP) in humans has not been quantitatively measured in epidemiologic studies., The persistence of deficits in motor strength in all severely poisoned patients regardless of pesticide type was unexpected, and may reflect persistent cholinergic blockade or intermediate syndrome, neuropathy, or a combination of these., The findings showed a strong association between exposure to OP concentrate and neurological symptoms, but a less consistent association with sensory thresholds. , Following accidental or suicidal exposure, these anticholinesterases lead to three well defined neurological syndromes i.e. initial life threatening acute cholinergic crisis which often requires management in intensive care unit, intermediate syndrome in which cranial nerve palsies, proximal muscle weakness and respiratory muscle weakness are common and patients often require respiratory support and delayed organophosphate induced polyneuropathy., [Late onset polyneuropathy due to exposure to organophosphates]., Less often a polyneuropathic syndrome of late onset may occur., On electromyography there was sensomotor peripheral polyneuropathy, which was primarily axonal and predominantly motor and distal. Peripheral nerve biopsy confirmed the presence of 'dying back' type axonopathy. , Agricultural workers chronically exposed to organophosphate insecticides, without adequate protection, have an increased risk of developing late onset neuropathy due to organophosphates. , Epidemiologic studies on pesticides have found associations with long-term effects on health mainly in three fields: cancer (especially hematological cancer), neurotoxic effects (polyneuropathy, neuro-behavioral hazards, Parkinson's disease), and reproductive disorders (infertility, birth defects, adverse pregnancy outcomes, perinatal mortality). , EMG studies showed evidence of partial denervation of the anterior tibial group of muscles and flexor digiti minimi in 2 of the 30 workers (6.7%) who underwent EMG examination., Neurological symptoms consist in cerebro-organic disfunctions, locomotory disorders reminiscent of multiple sclerosis or M. Parkinson, and sensory, motoric and vegetative polyneuropathy, leading, for instance, to cardiovascular regulatory disorder like sympathicotonia or, orthostatic hypotonia. , Thirty percent of patients had definite or possible exposure to organophosphate pesticides, and the peak use coincides with the peak incidence of Guillain-Barré syndrome., These results suggest that previously reported cases of organophosphate-induced delayed polyneuropathy may represent only the worst disease in a spectrum of impairment, a sequela of exposure that may be much more common than previously thought., It is suggested that the main cause of nervous lesions in these cases was the complex effect of pesticides., Delayed polyneuropathy develops within 1 to 3 weeks and abates after 6 to 12 months. , Isolated case reports have circumstantially linked the use of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) to polyneuropathy., Thus, the weight of evidence indicates that 2,4-D is an unlikely cause of polyneuropathy., A patient is reported presenting a cerebellar disorder developing about 5 weeks after acute exposure to an organophosphate insecticide. , Less well known, but more complex and idiosyncratic, is the potential for some agents to produce a delayed and progressive polyneuropathy--Organophosphorus Induced Delayed Neurotox-icity (OPIDN)., It is also quite probable that human neurotoxicity may be a potential hazard from exposure to more than the handful of organophosphorus pesticides that have been described in the literature., In the present study the electroencephalograms of 3 of a group 10 workmen, who had been continually exposed to hexachlorcyclohexane, show pathological findings. The electromyograms of 8 of these 10 workman demonstrate a disturbance of the peripherical motoneuron. All probands, who exhibit o pathological EEG, also show a polyneuropathy., Many organophosphorus compounds, including the organophosphate insecticides, may cause polyneuropathy of delayed onset., Nevertheless, we describe a patient with delayed polyneuropathy after suicidal ingestion of parathion., Following acute organophosphorus (OP) poisoning patients complain of numbness without objective sensory abnormalities or other features of OP induced delayed polyneuropathy. [SEP]Relations: polyneuropathy has relations: disease_disease with polyneuropathy due to drug, disease_disease with polyneuropathy due to drug, disease_disease with polyneuritis, disease_disease with polyneuritis, disease_disease with peripheral neuropathy, disease_disease with peripheral neuropathy, disease_disease with critical illness polyneuropathy, disease_disease with critical illness polyneuropathy, disease_disease with polyradiculoneuropathy, disease_disease with polyradiculoneuropathy. Definitions: chlorpyrifos defined as following: An organothiophosphate cholinesterase inhibitor that is used as an insecticide and as an acaricide.. DDVP defined as following: An organophosphorus insecticide that inhibits ACETYLCHOLINESTERASE.. cancer defined as following: A malignant tumor at the original site of growth.. sensory neuropathy defined as following: Inflammation or degeneration of the sensory nerves.. organophosphate defined as following: An ester of phosphoric acid, which contains phosphorus. Organic phosphates play important roles in biochemistry and biogeochemistry or ecology.. muscles defined as following: Contractile tissue that produces movement in animals.. malathion defined as following: A wide spectrum aliphatic organophosphate insecticide widely used for both domestic and commercial agricultural purposes.. Neuropathies defined as following: A disorder affecting the cranial nerves or the peripheral nervous system. It manifests with pain, tingling, numbness, and muscle weakness. It may be the result of physical injury, toxic substances, viral diseases, diabetes, renal failure, cancer, and drugs.. organochlorines defined as following: Hydrocarbon compounds with one or more of the hydrogens replaced by CHLORINE.. 2,4-D defined as following: An herbicide with irritant effects on the eye and the gastrointestinal system.. peripheral neuropathy defined as following: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.. organophosphorus insecticides defined as following: class of chemicals composed of an organic radical bound to a phosphorus containing radical that kill insects.. insecticides defined as following: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. poisonings defined as following: A condition or physical state produced by the ingestion, injection, inhalation of or exposure to a deleterious agent.. parathion defined as following: A highly toxic cholinesterase inhibitor that is used as an acaricide and as an insecticide.. neurotoxicity defined as following: Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.. pesticides defined as following: Chemicals used to destroy pests of any sort. The concept includes fungicides (FUNGICIDES, INDUSTRIAL); INSECTICIDES; RODENTICIDES; etc.. diaphragm defined as following: A medical contraceptive device of soft flexible material, usually of thin rubber, that is designed to cover the cervix uteri prior to sexual intercourse to prevent the entry of spermatozoa. To enhance efficacy, a spermicidal agent is often placed within the device. Antimicrobial agent(s) can also be used to prevent sexually transmitted diseases. Efficacy of vaginal diaphragm against infections is very limited.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. numbness defined as following: A loss of the sensation of feeling in an area of the body.. cholinergic defined as following: Any drug used for its actions on cholinergic systems. Included here are agonists and antagonists, drugs that affect the life cycle of ACETYLCHOLINE, and drugs that affect the survival of cholinergic neurons. The term cholinergic agents is sometimes still used in the narrower sense of MUSCARINIC AGONISTS, although most modern texts discourage that usage.. OPs defined as following: An autosomal recessive condition caused by homozygous or compound heterozygous inactivating mutation(s) in the gene LRP5, encoding low-density lipoprotein receptor-related protein 5. This condition is characterized by severe juvenile-onset osteoporosis and congenital or juvenile-onset blindness due to a vascularized retinal mass that resembles a glioma.. muscle weakness defined as following: A vague complaint of debility, fatigue, or exhaustion attributable to weakness of various muscles. The weakness can be characterized as subacute or chronic, often progressive, and is a manifestation of many muscle and neuromuscular diseases. (From Wyngaarden et al., Cecil Textbook of Medicine, 19th ed, p2251). multiple sclerosis defined as following: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903). poisoning defined as following: Used with drugs, chemicals, and industrial materials for human or animal poisoning, acute or chronic, whether the poisoning is accidental, occupational, suicidal, by medication error, or by environmental exposure.. cerebellar disorder defined as following: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, GAIT ATAXIA, and MUSCLE HYPOTONIA.. paresthesia defined as following: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation.. neck muscles defined as following: The neck muscles consist of the platysma, splenius cervicis, sternocleidomastoid(eus), longus colli, the anterior, medius, and posterior scalenes, digastric(us), stylohyoid(eus), mylohyoid(eus), geniohyoid(eus), sternohyoid(eus), omohyoid(eus), sternothyroid(eus), and thyrohyoid(eus).. organophosphorus compounds defined as following: Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS.. Guillain-Barré syndrome defined as following: An acute inflammatory autoimmune neuritis caused by T cell- mediated cellular immune response directed towards peripheral myelin. Demyelination occurs in peripheral nerves and nerve roots. The process is often preceded by a viral or bacterial infection, surgery, immunization, lymphoma, or exposure to toxins. Common clinical manifestations include progressive weakness, loss of sensation, and loss of deep tendon reflexes. Weakness of respiratory muscles and autonomic dysfunction may occur. (From Adams et al., Principles of Neurology, 6th ed, pp1312-1314). polyneuropathies defined as following: Diseases of multiple peripheral nerves simultaneously. Polyneuropathies usually are characterized by symmetrical, bilateral distal motor and sensory impairment with a graded increase in severity distally. The pathological processes affecting peripheral nerves include degeneration of the axon, myelin or both. The various forms of polyneuropathy are categorized by the type of nerve affected (e.g., sensory, motor, or autonomic), by the distribution of nerve injury (e.g., distal vs. proximal), by nerve component primarily affected (e.g., demyelinating vs. axonal), by etiology, or by pattern of inheritance.. birth defects defined as following: Malformations of organs or body parts during development in utero.. cranial nerve palsies defined as following: Injury to any of the cranial nerves or their nuclei in the brain resulting in muscle weakness.. humans defined as following: Members of the species Homo sapiens.. cranial nerves defined as following: Twelve pairs of nerves that carry general afferent, visceral afferent, special afferent, somatic efferent, and autonomic efferent fibers.. infertility defined as following: Complete inability to conceive or induce conception.. Parkinson's disease defined as following: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75). polyneuropathy defined as following: Diseases of multiple peripheral nerves simultaneously. Polyneuropathies usually are characterized by symmetrical, bilateral distal motor and sensory impairment with a graded increase in severity distally. The pathological processes affecting peripheral nerves include degeneration of the axon, myelin or both. The various forms of polyneuropathy are categorized by the type of nerve affected (e.g., sensory, motor, or autonomic), by the distribution of nerve injury (e.g., distal vs. proximal), by nerve component primarily affected (e.g., demyelinating vs. axonal), by etiology, or by pattern of inheritance..", "label": "yes"} {"id": "converted_4352", "sentence1": "Does atemoya juice inhibit tye CYP3A4 enzyme?", "sentence2": "Atemoya juice significantly inhibited CYP1A2 activity in human liver microsomes, but not the activities of CYP2C9 and CYP3A.[SEP]Relations: cytochrome P450 4A1-heme linkage has relations: bioprocess_bioprocess with protein-heme linkage, bioprocess_bioprocess with protein-heme linkage. deficiency of coenzyme q cytochrome c reductase has relations: disease_disease with inborn errors of metabolism, disease_disease with inborn errors of metabolism. Definitions: CYP2C9 defined as following: A cytochrome P-450 subtype that has specificity for acidic XENOBIOTICS. It oxidizes a broad range of important clinical drugs that fall under the categories of NONSTEROIDAL ANTI-INFLAMMATORY AGENTS; HYPOGLYCEMIC AGENTS; ANTCOAGULANTS; and DIURETICS.. CYP3A defined as following: A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.. human defined as following: Members of the species Homo sapiens..", "label": "no"} {"id": "converted_1347", "sentence1": "Is the protein product of the cylindromatosis gene (CYLD) a deubiquitinating enzyme?", "sentence2": "CYLD was originally identified as a tumor suppressor gene mutated in familial cylindromatosis, an autosomal dominant predisposition to multiple benign neoplasms of the skin known as cylindromas. The CYLD protein is a deubiquitinating enzyme that acts as a negative regulator of NF-κB and JNK signaling through its interaction with NEMO and TNFR-associated factor 2., CYLD, a deubiquitinating enzyme (DUB), is a critical regulator of diverse cellular processes, ranging from proliferation and differentiation to inflammatory responses, via regulating multiple key signaling cascades such as nuclear factor kappa B (NF-κB) pathway., CYLD is a lysine 63-deubiquitinating enzyme that inhibits NF-κB and JNK signaling., Tumor suppressor gene CYLD is a deubiquitinating enzyme which negatively regulates various signaling pathways by removing the lysine 63-linked polyubiquitin chains from several specific substrates., The cylindromatosis tumor suppressor (CYLD) is a deubiquitinating enzyme that has been implicated in various aspects of adaptive and innate immune responses. , The cylindromatosis gene (CYLD) was identified as a tumor suppressor gene, which is mutated in familial cylindromatosis (Brooke-Spiegler syndrome), an autosomal-dominant predisposition to multiple tumors of the skin appendages. CYLD is a deubiquitinating enzyme acting as a negative regulator of the nuclear factor κB (NF-κB) signaling pathway by removing lysine-63-linked polyubiquitin chains from NF-κB activating proteins. , Here, we identify the deubiquitinating enzyme CYLD, the familial cylindromatosis tumor suppressor gene, as a negative regulator of proximal events in Wnt/beta-catenin signaling., CYLD is a tumour-suppressor gene that is mutated in a benign skin tumour syndrome called cylindromatosis. The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-kappaB signalling., Cyld encodes a 956-amino acid deubiquitinating enzyme (CYLD), which is a negative regulator of nuclear factor kappaB and mitogen-activated protein kinase pathways., The deubiquitinating enzyme CYLD has been identified as a key negative regulator for NF-kappaB. , CYLD, a tumor suppressor gene, has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB. Loss of the deubiquitinating activity of CYLD is correlated with tumorigenesis., We show that dCYLD encodes a deubiquitinating enzyme that deubiquitinates dTRAF2 and prevents dTRAF2 from ubiquitin-mediated proteolytic degradation., The CYLD gene encodes a deubiquitinating enzyme that removes Lys-63-linked ubiquitin chains from I kappa B kinase signaling components and thereby inhibits NF-kappaB pathway activation., Deubiquitinating enzymes (DUB) form a family of cysteine proteases that digests ubiquitin chains and reverses the process of protein ubiquitination. Despite the identification of a large number of DUBs, their physiological functions remain poorly defined. Here we provide genetic evidence that CYLD, a recently identified DUB, plays a crucial role in regulating the peripheral development and activation of B cells., The cylindromatosis (CYLD) gene was originally identified as a tumor suppressor that is mutated in familial cylindromatosis, an autosomal dominant condition that confers a predisposition to multiple tumors of the skin appendages. CYLD has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB. Therefore, loss of CYLD function correlates with tumorigenesis., Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-κB signaling pathway and attenuates NF-κB and JNK signaling., The cylindromatosis tumor suppressor gene (Cyld) encodes a deubiquitinating enzyme (CYLD) with immunoregulatory function., The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-kappaB signalling., Here, we examined the potential role of the deubiquitinating enzyme CYLD (cylindromatosis), mutation of which has been reported to cause familial cylindromatosis., The deubiquitinating enzyme cylindromatosis (CYLD), loss of which was originally reported to cause a benign human syndrome called cylindromatosis, has been identified as a key negative regulator for NF-kappaB in vitro., The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-kappaB signalling., Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-�B signaling pathway and attenuates NF-�B and JNK signaling., Cylindromatosis (CYLD) is a deubiquitinating enzyme that is altered in patients with familial cylindromatosis, a condition characterized by numerous benign adnexal tumors., CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members., Here, we identify the deubiquitinating enzyme CYLD, the familial cylindromatosis tumor suppressor gene, as a negative regulator of proximal events in Wnt/beta-catenin signaling, Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-κB signaling pathway and attenuates NF-κB and JNK signaling, The CYLD gene product is a deubiquitinating enzyme that was shown to regulate cell proliferation, cell survival and inflammatory responses, mainly through inhibiting NF-kappaB signalling, The cylindromatosis tumor suppressor gene (Cyld) encodes a deubiquitinating enzyme (CYLD) with immunoregulatory function, Cylindromatosis gene (CYLD) is a ubiquitously expressed deubiquitinating enzyme, which interacts with members of the NF-κB signaling pathway and attenuates NF-κB and JNK signaling, The cylindromatosis tumor suppressor gene (Cyld) encodes an enzyme (CYLD) with deubiquitinating activity that has been implicated in the regulation of thymocyte selection in an NF-κB-essential-modulator (NEMO)-dependent manner, Here, we identify the deubiquitinating enzyme CYLD, the familial cylindromatosis tumor suppressor gene, as a negative regulator of proximal events in Wnt/beta-catenin signaling, CYLD is a deubiquitinating enzyme acting as a negative regulator of the nuclear factor κB (NF-κB) signaling pathway by removing lysine-63-linked polyubiquitin chains from NF-κB activating proteins, CYLD, a tumor suppressor gene, has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB, Here, we examined the potential role of the deubiquitinating enzyme CYLD (cylindromatosis), mutation of which has been reported to cause familial cylindromatosis, CYLD has deubiquitinating enzyme activity and inhibits the activation of transcription factor NF-kappaB[SEP]Relations: Cysteine has relations: drug_protein with MGMT, drug_protein with MGMT, drug_protein with GOT2, drug_protein with GOT2, drug_protein with CSAD, drug_protein with CSAD. Brooke-Spiegler syndrome has relations: disease_protein with CYLD, disease_protein with CYLD. adenoid cystic carcinoma has relations: disease_protein with SOX11, disease_protein with SOX11. Definitions: CYLD gene defined as following: This gene is involved in protein deubiquitination.. Cyld defined as following: Ubiquitin carboxyl-terminal hydrolase CYLD (956 aa, ~107 kDa) is encoded by the human CYLD gene. This protein is involved in the mediation of protein deubiquitination and the regulation of the cell cycle.. NEMO defined as following: NF-kappa-B essential modulator (419 aa, ~48 kDa) is encoded by the human IKBKG gene. This protein plays a role in the mediation of signal transduction through protein phosphorylation.. cysteine proteases defined as following: A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.. B cells defined as following: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.. TNFR defined as following: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.. nuclear factor kappa B defined as following: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. cylindromas defined as following: Carcinoma characterized by bands or cylinders of hyalinized or mucinous stroma separating or surrounded by nests or cords of small epithelial cells. When the cylinders occur within masses of epithelial cells, they give the tissue a perforated, sievelike, or cribriform appearance. Such tumors occur in the mammary glands, the mucous glands of the upper and lower respiratory tract, and the salivary glands. They are malignant but slow-growing, and tend to spread locally via the nerves. (Dorland, 27th ed). Deubiquitinating enzymes defined as following: Enzymes that remove UBIQUITIN from a protein substrate, including POLYUBIQUITIN, or from other molecules.. CYLD protein defined as following: A deubiquitinase and tumor-suppressor protein that specifically cleaves LYSINE-63-linked polyubiquitin chains and also has endodeubiquitinase activity. It functions to regulate NF-KAPPA B and WNT SIGNALING PATHWAY activity, contributing to cell survival, proliferation, and differentiation. Mutations in the CYLD gene are associated with cases of FAMILIAL CYLINDROMATOSIS.. nuclear factor κB defined as following: A family of proteins that contain 1 DWA/MH1 domain and bind 5'-TTGGCNNNNNGCCAA-3' DNA palindromes in viral and cellular promoters as homodimeric factors capable of activating transcription and replication.. Brooke-Spiegler syndrome defined as following: A rare genetic disease characterized as an inherited skin tumour predisposition syndrome presenting with skin appendage tumours, namely cylindromas, spiradenomas and trichoepitheliomas. tumor suppressor gene defined as following: Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.. CYLD defined as following: Ubiquitin carboxyl-terminal hydrolase CYLD (956 aa, ~107 kDa) is encoded by the human CYLD gene. This protein is involved in the mediation of protein deubiquitination and the regulation of the cell cycle..", "label": "yes"} {"id": "converted_1131", "sentence1": "Do conserved noncoding elements co-occur with matrix-attachment regions?", "sentence2": "We hypothesized that some of these regions might be matrix-scaffold attachment regions, MARs (or S/MARs). MARs comprise one of the few classes of eukaryotic noncoding DNA with an experimentally characterized function, being involved in the attachment of chromatin to the nuclear matrix, chromatin remodeling and transcription regulation. To test our hypothesis, we analyzed the co-occurrence of predicted MARs with highly conserved noncoding DNA regions in human-mouse genomic alignments. We found that 11% of the conserved noncoding DNA consists of predicted MARs. Conversely, more than half of the predicted MARs co-occur with one or more independently identified conserved sequence blocks. An excess of conserved predicted MARs is seen in intergenic regions preceding 5' ends of genes, suggesting that these MARs are primarily involved in transcriptional control, A significant fraction of conserved noncoding DNA in human and mouse consists of predicted matrix attachment regions., To test our hypothesis, we analyzed the co-occurrence of predicted MARs with highly conserved noncoding DNA regions in human-mouse genomic alignments., To test our hypothesis, we analyzed the co-occurrence of predicted MARs with highly conserved noncoding DNA regions in human-mouse genomic alignments[SEP]Relations: nuclear matrix has relations: cellcomp_protein with NONO, cellcomp_protein with NONO, cellcomp_protein with RNASEL, cellcomp_protein with RNASEL, cellcomp_protein with PPIG, cellcomp_protein with PPIG, cellcomp_protein with DCAF7, cellcomp_protein with DCAF7, cellcomp_protein with RGS12, cellcomp_protein with RGS12. Definitions: MARs defined as following: The fourth planet in order from the sun. Its two natural satellites are Deimos and Phobos. It is one of the four inner or terrestrial planets of the solar system.. human defined as following: Members of the species Homo sapiens.. nuclear matrix defined as following: The residual framework structure of the CELL NUCLEUS that maintains many of the overall architectural features of the cell nucleus including the nuclear lamina with NUCLEAR PORE complex structures, residual CELL NUCLEOLI and an extensive fibrogranular structure in the nuclear interior. (Advan. Enzyme Regul. 2002; 42:39-52). chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"} {"id": "converted_4152", "sentence1": "Are there sex differences in oncogenic mutational processes?", "sentence2": "Sex differences in oncogenic mutational processes.[SEP]", "label": "yes"} {"id": "converted_471", "sentence1": "Is there a crystal structure of the full-length of the flaviviridae NS5(Methyltransferase - RNA depended RNA Polymerase) ?", "sentence2": " flavivirus NS5 harbors a methyltransferase (MTase) in its N-terminal ≈ 265 residues and an RNA-dependent RNA polymerase (RdRP) within the C-terminal part. One of the major interests and challenges in NS5 is to understand the interplay between RdRP and MTase as a unique natural fusion protein in viral genome replication and cap formation. Here, we report the first crystal structure of the full-length flavivirus NS5 from Japanese encephalitis virus. , (DENV) nonstructural protein 5 (NS5) is composed of two globular domains separated by a 10-residue linker. The N-terminal domain participates in the synthesis of a mRNA cap 1 structure ((7Me)GpppA(2'OMe)) at the 5' end of the viral genome and possesses guanylyltransferase, guanine-N7-methyltransferase, and nucleoside-2'O-methyltransferase activities. The C-terminal domain is an RNA-dependent RNA polymerase responsible for viral RNA synthesis. Although crystal structures of the two isolated domains have been obtained, there are no structural data for full-length NS5. It is also unclear whether the two NS5 domains interact with each other to form a stable structure in which the relative orientation of the two domains is fixed. To investigate the structure and dynamics of DENV type 3 NS5 in solution, we conducted small-angle X-ray scattering experiments with the full-length protein. NS5 was found to be monomeric and well-folded under the conditions tested., West Nile virus (WNV) NS5 protein contains a methyltransferase (MTase) domain involved in RNA capping and an RNA-dependent RNA polymerase (RdRp) domain essential for virus replication. Crystal structures of individual WNV MTase and RdRp domains have been solved; however, the structure of full-length NS5 has not been determined. To gain more insight into the structure of NS5 and interactions between the MTase and RdRp domains, we generated a panel of seven monoclonal antibodies (mAbs) to the NS5 protein of WNV (Kunjin strain) and mapped their binding sites using a series of truncated NS5 proteins and synthetic peptides. Binding sites of four mAbs (5D4, 4B6, 5C11 and 6A10) were mapped to residues 354-389 in the fingers subdomain of the RdRp. This is consistent with the ability of these mAbs to inhibit RdRp activity in vitro and suggests that this region represents a potential target for RdRp inhibitors. Using a series of synthetic peptides, we also identified a linear epitope (bound by mAb 5H1) that mapped to a 13 aa stretch surrounding residues 47 and 49 in the MTase domain, a region predicted to interact with the palm subdomain of the RdRp. The failure of one mAb (7G6) to bind both N- and C-terminally truncated NS5 recombinants indicates that the antibody recognizes a conformational epitope that requires the presence of residues in both the MTase and RdRp domains. [SEP]Relations: RNA-directed DNA polymerase activity has relations: molfunc_protein with TERC, molfunc_protein with TERC, molfunc_protein with ERVK-7, molfunc_protein with ERVK-7, molfunc_protein with ERVK-6, molfunc_protein with ERVK-6, molfunc_protein with ERVK-8, molfunc_protein with ERVK-8, molfunc_protein with TERT, molfunc_protein with TERT. Definitions: binding sites defined as following: The parts of a macromolecule that directly participate in its specific combination with another molecule.. RNA defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). NS5 defined as following: Noonan syndrome caused by autosomal dominant mutation(s) in the RAF1 gene, encoding RAF proto-oncogene serine/threonine-protein kinase.. WNV defined as following:West Nile virus (WNV) is an infectious disease that first appeared in the United States in 1999. Infected mosquitoes spread the virus that causes it. People who get WNV usually have no symptoms or mild symptoms. The symptoms include a fever, headache, body aches, skin rash, and swollen lymph glands. They can last a few days to several weeks, and usually go away on their own.
If West Nile virus enters the brain, however, it can be life-threatening. It may cause inflammation of the brain, called encephalitis, or inflammation of the tissue that surrounds the brain and spinal cord, called meningitis. A physical exam, medical history, and laboratory tests can diagnose it.
Older people and those with weakened immune systems are most at risk. There are no specific vaccines or treatments for human WNV disease. The best way to avoid WNV is to prevent mosquito bites:
Participant material that is brought forth (produced) in the act (e.g., specimen in a specimen collection, access or drainage in a placement service, medication package in a dispense service). It does not matter whether the material produced had existence prior to the service, or whether it is created in the service (e.g., in supply services the product is taken from a stock).
. tumor cell defined as following: Cells of, or derived from, a tumor.. extracellular matrix defined as following: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.. mammary defined as following: Glandular tissue in the BREAST of human that is under the influence of hormones such as ESTROGENS; PROGESTINS; and PROLACTIN. In WOMEN, after PARTURITION, the mammary glands secrete milk (MILK, HUMAN) for the nourishment of the young.. lgl defined as following: A form of ventricular pre-excitation characterized by a short PR interval and a normal QRS complex. In this syndrome, the atrial impulse conducts via the JAMES FIBERS which connect the atrium to BUNDLE OF HIS bypassing the upper ATRIOVENTRICULAR NODE. HEART VENTRICLES are depolarized normally through the His-Purkinje system.. hepatocellular carcinoma defined as following: A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.. SCRIB defined as following: This gene is involved in the establishment of cell polarity..", "label": "yes"} {"id": "converted_3570", "sentence1": "Is palbociclib effective for glioblastoma?", "sentence2": "Although further research is needed, cyclin-dependent kinase 4/6 inhibitors represent intriguing developments in the treatment of various malignancies, including those with such poor prognoses as glioblastoma multiforme, mantle cell lymphoma, and metastatic melanoma., CONCLUSION: In this trial, despite adequate tissue PK, palbociclib monotherapy was not an effective treatment for recurrent glioblastoma., CONCLUSION\n\nIn this trial, despite adequate tissue PK, palbociclib monotherapy was not an effective treatment for recurrent glioblastoma., CONCLUSION In this trial, despite adequate tissue PK, palbociclib monotherapy was not an effective treatment for recurrent glioblastoma., CONCLUSION\nIn this trial, despite adequate tissue PK, palbociclib monotherapy was not an effective treatment for recurrent glioblastoma.[SEP]Relations: adult glioblastoma has relations: disease_disease with glioblastoma (disease), disease_disease with glioblastoma (disease), disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult spinal cord glioblastoma, disease_disease with adult spinal cord glioblastoma. mantle cell lymphoma has relations: disease_protein with CREBBP, disease_protein with CREBBP, disease_protein with UBR5, disease_protein with UBR5. Definitions: mantle cell lymphoma defined as following: A form of non-Hodgkin lymphoma having a usually diffuse pattern with both small and medium lymphocytes and small cleaved cells. It accounts for about 5% of adult non-Hodgkin lymphomas in the United States and Europe. The majority of mantle-cell lymphomas are associated with a t(11;14) translocation resulting in overexpression of the CYCLIN D1 gene (GENES, BCL-1).. malignancies defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. PK defined as following: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.. glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO). cyclin-dependent kinase defined as following: This gene is involved in the cellular transition from the G1/S phase and from the G2/M phase of the cell cycle..", "label": "no"} {"id": "converted_1391", "sentence1": "Can RNASeq be used for the analysis of nascent transcripts?", "sentence2": "Here, we utilize nascent RNA sequencing to document dosage compensation during transcriptional elongation., Here we show that RNA-seq can also be used for studying nascent RNAs undergoing transcription, Conversely, the nuclear fraction shows an enrichment of unprocessed RNA compared with total RNA-seq, making it suitable for analysis of nascent transcripts and RNA processing dynamics.[SEP]Definitions: RNA defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed).", "label": "yes"} {"id": "converted_142", "sentence1": "Is amiodarone a class I anti-arrhythmic drug?", "sentence2": "Common class I agents are excluded due to the inherent abnormal cardiac structure and function in the setting of cardiogenic shock. Class III drug options include dofetilide and amiodarone., Amiodarone has been used as an anti-arrhythmic drug since the 1970s and has an established role in the treatment of ventricular tachyarrhythmias. Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile. , Amiodarone, an iodinated benzofuran derivative, introduced in 1960's as an anti-anginal agent, emerged as a potent anti-arrhythmic agent by 1970's and is currently one of the most commonly prescribed drugs in US for ventricular and atrial arrhythmias. Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent., Amiodarone, a representative class III agent, exerts negative dromotropism by suppressing the fast sodium current responsible for conduction in acute administration (class I effects). Chronic amiodarone causes prolongation of ERP (class III effects), which is sometimes associated with negative dromotropism based on the alteration of passive or active membrane properties., Amiodarone, an iodinated benzofuran derivative with predominantly class III anti-arrhythmic effects, is used to treat supraventricular and ventricular arrhythmias., Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent, Amiodarone, a class III antiarrhythmic drug, is one of the most effective drugs used in the treatment of ventricular and paroxysmal supraventricular tachyarrhythmia, Although amiodarone is considered a class III anti-arrhythmic agent, it also has class I, II, IV actions, making it a unique and effective anti-arrhythmic agent, Although considered to be a class III anti-arrhythmic, amiodarone also has class I, II and IV actions, which gives it a unique pharmacological and anti-arrhythmic profile, Amiodarone is a potent class III anti-arrhythmic drug that also possesses beta-blocking properties[SEP]Relations: Amiodarone has relations: drug_effect with Arrhythmia, drug_effect with Arrhythmia, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Erythromycin, drug_drug with Erythromycin, drug_drug with Arformoterol, drug_drug with Arformoterol, drug_drug with Estrone, drug_drug with Estrone. Definitions: dofetilide defined as following: A sulfonamide class III antiarrhythmic agent and potassium channel blocker. Dofetilide selectively blocks cardiac ion channels of the rapid component of the delayed rectifier potassium current Ikr. This antiarrhythmic agent prolongs cardiac action potential duration and effective refractory period due to delayed repolarization without affecting conduction velocity. This results in a normal sinus rhythm. Dofetilide is used in the treatment of atrial fibrillation and flutter.. ERP defined as following: Fiberoptic endoscopy designed for duodenal observation and cannulation of VATER'S AMPULLA, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (Vater) papillotomy (SPHINCTEROTOMY, ENDOSCOPIC) may be performed during this procedure.. anti-arrhythmic agent defined as following: Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.. benzofuran defined as following: Compounds that contain a BENZENE ring fused to a furan ring.. amiodarone defined as following: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.. ventricular arrhythmias defined as following: A disorder characterized by an electrocardiographic finding of an atypical cardiac rhythm resulting from a pathologic process in the cardiac ventricles.. cardiogenic shock defined as following: Shock resulting from diminution of cardiac output in heart disease.. class I defined as following: A grading of angina such that ordinary physical activity, such as walking or climbing stairs, does not cause angina. Angina occurs with strenuous, rapid, or prolonged exertion at work or recreation.. class III defined as following: A grading of angina characterized by marked limitations of ordinary physical activity. Angina occurs on walking 1 to 2 blocks on the level and climbing 1 flight of stairs in normal conditions and at a normal pace.. atrial arrhythmias defined as following: An electrocardiographic finding of an atypical cardiac rhythm resulting from a pathologic process in the cardiac atria..", "label": "no"} {"id": "converted_2786", "sentence1": "Do yeast LTR give rise to circular DNA?", "sentence2": "Circular retrotransposition products generated by a LINE retrotransposon, Formation of Extrachromosomal Circular DNA from Long Terminal Repeats of Retrotransposons in Saccharomyces cerevisiae, Ty eccDNA can arise from the circularization of extrachromosomal linear DNA during the transpositional life cycle of retrotransposons, or from circularization of genomic Ty DNA, Circularization may happen through nonhomologous end-joining (NHEJ) of long terminal repeats (LTRs) flanking Ty elements, by Ty autointegration, or by LTR-LTR recombination, We have recently shown that yeast LTR elements generate circular DNAs through recombination events between their flanking long terminal repeats (LTRs)., Similarly, circular DNAs can be generated by recombination between LTRs residing at different genomic loci, in which case the circular DNA will contain the intervening sequence., A recent study on circular DNAs in yeast found that transposable element sequence residing in circular structures mostly corresponded to full-length transposable elements.[SEP]Relations: Nonhomologous End-Joining (NHEJ) has relations: pathway_protein with XRCC6, pathway_protein with XRCC6, pathway_protein with XRCC5, pathway_protein with XRCC5, pathway_protein with RAD50, pathway_protein with RAD50, pathway_protein with XRCC4, pathway_protein with XRCC4, pathway_protein with TDP2, pathway_protein with TDP2. Definitions: long terminal repeats defined as following: Identical DNA sequences found at either end of retrovirus proviral DNA, formed by reverse transcription of viral RNA.. circular DNA defined as following: Any of the covalently closed DNA molecules found in bacteria, many viruses, mitochondria, plastids, and plasmids. Small, polydisperse circular DNA's have also been observed in a number of eukaryotic organisms and are suggested to have homology with chromosomal DNA and the capacity to be inserted into, and excised from, chromosomal DNA. It is a fragment of DNA formed by a process of looping out and deletion, containing a constant region of the mu heavy chain and the 3'-part of the mu switch region. Circular DNA is a normal product of rearrangement among gene segments encoding the variable regions of immunoglobulin light and heavy chains, as well as the T-cell receptor. (Riger et al., Glossary of Genetics, 5th ed & Segen, Dictionary of Modern Medicine, 1992). yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. NHEJ defined as following: The repair of a double-strand break in DNA in which the two broken ends are rejoined with little or no sequence complementarity. Information at the DNA ends may be lost due to the modification of broken DNA ends. This term covers instances of separate pathways, called classical (or canonical) and alternative nonhomologous end joining (C-NHEJ and A-NHEJ). These in turn may further branch into sub-pathways, but evidence is still unclear. [GOC:rph, PMID:10827453, PMID:24837021]. intervening sequence defined as following: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes..", "label": "yes"} {"id": "converted_3030", "sentence1": "Is avelumab effective for bladder cancer?", "sentence2": "BACKGROUND: Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma., Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab) and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hodgkin's lymphoma. , The Food and Drug Administration has already approved a number of checkpoint inhibitors such as anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibodies including ipilimumab; anti-PD-1 monoclonal antibodies including nivolumab and pembrolizumab; anti-PD-L1 antibodies including atezolizumab, avelumab, and durvalumab. , Five immune CPI have recently been approved for aUC/mUC by the US Food and Drug Administration (FDA) including atezolizumab, nivolumab, pembrolizumab, durvalumab and avelumab. , RECENT FINDINGS: Since May 2016, five different agents targeting the PD-1/PD-L1 pathway (atezolizumab, pembrolizumab, nivolumab, avelumab, durvalumab) have received FDA approval for the treatment of aUC in the platinum-refractory setting, while pembrolizumab and atezolizumab are FDA-approved for cisplatin-ineligible patients in the first-line setting., Avelumab for the treatment of urothelial cancer., Avelumab, a PD-1 ligand (PD-L1) inhibitor, is currently being investigated for the treatment of UC. Areas covered: This article will review the pharmacological characteristics of avelumab, the efficacy studies which led to its approval, its safety profile, as well as its place within the management of urothelial carcinoma with immunotherapy. , Expert commentary: Avelumab has shown promising antitumor activity and a manageable safety profile in patients with UC. , Atezolizumab is the only member of this class currently approved for the treatment of bladder cancer, but nivolumab, pembrolizumab, durvalumab, and avelumab all have positive results for this indication, and approvals are anticipated in the near future., This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab., Atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab are promising PD-1/PD-L1 blockade drugs under investigation that will redefine the standard of care for bladder cancer., Monoclonal antibodies that target programmed cell death protein 1 (PD-1), including Nivolumab and Pembrolizumab, and its ligand, PD-L1, including Atezolizumab, Durvalumab, Avelumab, have all been investigated and approved in the setting of metastatic refractory urothelial cancer (Gupta et al., Six drugs including one CTLA-4 blocker (ipilimumab), two PD-1 blockers (nivolumab and pembrolizumab) and three PD-L1 blockers (atezolizumab, avelumab and durvalumab) are approved for the treatment of different types of cancers including both solid tumors such as melanoma, lung cancer, head and neck cancer, bladder cancer and Merkel cell cancer as well as hematological tumors such as classic Hodgkin's lymphoma., Nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab are among the exciting recent novel therapeutic advances gaining approvals by the FDA for treatment of advanced-stage urothelial carcinoma.[SEP]Relations: Durvalumab has relations: drug_drug with Avelumab, drug_drug with Avelumab, drug_drug with Emapalumab, drug_drug with Emapalumab, drug_drug with Utomilumab, drug_drug with Utomilumab. Ipilimumab has relations: drug_drug with Avelumab, drug_drug with Avelumab. Nivolumab has relations: drug_drug with Avelumab, drug_drug with Avelumab. Definitions: Merkel cell carcinoma defined as following: A carcinoma arising from MERKEL CELLS located in the basal layer of the epidermis and occurring most commonly as a primary neuroendocrine carcinoma of the skin. Merkel cells are tactile cells of neuroectodermal origin and histologically show neurosecretory granules. The skin of the head and neck are a common site of Merkel cell carcinoma, occurring generally in elderly patients. (Holland et al., Cancer Medicine, 3d ed, p1245). Nivolumab defined as following: A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Upon administration, nivolumab binds to and blocks the activation of PD-1, an immunoglobulin superfamily (IgSF) transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). This results in the activation of T-cells and cell-mediated immune responses against tumor cells. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity.. aUC defined as following: A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992). Durvalumab defined as following: A monoclonal antibody directed against B7H1 (B7 homolog 1; programmed cell death ligand 1) with potential immunostimulating activity. Upon intravenous administration, durvalumab binds to the cell surface antigen B7H1, thereby blocking B7H1 signaling. This may activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response against B7H1-expressing tumor cells. B7H1, a member of the B7 protein superfamily and a negative regulator of cytokine synthesis, is overexpressed on certain tumor cell types.. CTLA4 defined as following: Human CTLA4 wild-type allele is located within 2q33 and is approximately 6 kb in length. This allele, which encodes cytotoxic T-lymphocyte protein 4, is involved in signal transduction and T-cell regulation. Variant alleles generated from mutations in the gene, have been associated with insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-associated orbitopathy, and other autoimmune diseases.. Bladder Cancer defined as following: A primary or metastatic malignant neoplasm involving the bladder.. ipilimumab defined as following: A recombinant human immunoglobulin (Ig) G1 monoclonal antibody directed against the human T-cell receptor cytotoxic T-lymphocyte-associated antigen 4 (CTLA4), with immune checkpoint inhibitory and antineoplastic activities. Ipilimumab binds to CTLA4 expressed on T-cells and inhibits the CTLA4-mediated downregulation of T-cell activation. This leads to a cytotoxic T-lymphocyte (CTL)-mediated immune response against cancer cells. CTLA4, an inhibitory receptor and member of the immunoglobulin superfamily, plays a key role in the downregulation of the immune system.. hematological tumors defined as following: Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.. PD-1 defined as following: Human PDCD1 wild-type allele is located in the vicinity of 2q37.3 and is approximately 9 kb in length. This allele, which encodes programmed cell death protein 1, plays a role in the modulation of both apoptosis and cellular immunity. Mutation of the gene is associated with systemic lupus erythematosus type 2.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. UC defined as following: Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.. urothelial carcinoma defined as following: A malignant neoplasm derived from the transitional epithelium of the urinary tract (urinary bladder, ureter, urethra, or renal pelvis). It is frequently papillary.. Monoclonal antibodies defined as following: Antibodies produced by a single clone of cells.. PD-L1 defined as following: Human CD274 wild-type allele is located in the vicinity of 9p24 and is approximately 20 kb in length. This allele, which encodes programmed cell death 1 ligand 1 protein, plays a role in the regulation of T cell stimulation and proliferation.. melanoma defined as following: A benign or malignant, primary or metastatic neoplasm affecting the melanocytes.. head and neck cancer defined as following: A primary or metastatic malignant neoplasm affecting the head and neck. Representative examples include oral cavity squamous cell carcinoma, laryngeal squamous cell carcinoma, and salivary gland carcinoma.. solid tumors defined as following: A benign or malignant neoplasm arising from tissues that do not include fluid areas. Representative examples include epithelial neoplasms (e.g. lung carcinoma, prostate carcinoma, breast carcinoma, colon carcinoma), and neoplasms arising from the soft tissues and bones (e.g. leiomyosarcoma, liposarcoma, chondrosarcoma, osteosarcoma). Neoplasms originating from the blood or bone marrow (leukemias and myeloproliferative disorders) are not considered solid tumors.. bladder cancer defined as following: A primary or metastatic malignant neoplasm involving the bladder..", "label": "yes"} {"id": "converted_3475", "sentence1": "Is the protein ABCG2 (ATP-Binding Cassette, subfamily G, member 2, transporter) excreting uric acid?", "sentence2": "TP-binding cassette transporter, sub-family G, member 2 (ABCG2/BCRP) is a well-studied urate transporter expressed on apical membranes in several tissues, including the intestine, liver, and kidney., the discovery that ABCG2 plays a central role on extra-renal uric acid excretion,[SEP]Relations: intestine has relations: anatomy_protein_present with ABCG2, anatomy_protein_present with ABCG2, anatomy_protein_present with ABCA2, anatomy_protein_present with ABCA2, anatomy_protein_present with ABCG1, anatomy_protein_present with ABCG1, anatomy_protein_present with ABCC2, anatomy_protein_present with ABCC2, anatomy_protein_present with ABCC6P2, anatomy_protein_present with ABCC6P2. Definitions: ABCG2 defined as following: Human ABCG2 wild-type allele is located within 4q22 and is approximately 67 kb in length. This allele, which encodes ATP-binding cassette sub-family G member 2 protein, plays a role in transmembrane transport and transcriptional regulation. The allele is thought to play a role in cellular defense and aberrations are thought to play a role in tumor multidrug resistance.. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. intestine defined as following: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.. uric acid defined as following: An oxidation product, via XANTHINE OXIDASE, of oxypurines such as XANTHINE and HYPOXANTHINE. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals URATE OXIDASE further oxidizes it to ALLANTOIN.. ATP-Binding Cassette defined as following: This gene plays a role in intracellular cholesterol transport..", "label": "yes"} {"id": "converted_3556", "sentence1": "Is GRG5 involved only in late embryonic mouse development?", "sentence2": "Groucho related gene 5 (GRG5) is a multifunctional protein that has been implicated in late embryonic and postnatal mouse development. Here, we describe a previously unknown role of GRG5 in early developmental stages by analyzing its function in stem cell fate decisions. By both loss and gain of function approaches we demonstrate that ablation of GRG5 deregulates the Embryonic Stem Cell (ESC) pluripotent state whereas its overexpression leads to enhanced self-renewal and acquisition of cancer cell-like properties. The malignant characteristics of teratomas generated by ESCs that overexpress GRG5 reveal its pro-oncogenic potential. [SEP]Relations: HSD17B4 has relations: anatomy_protein_present with embryo, anatomy_protein_present with embryo, bioprocess_protein with Sertoli cell development, bioprocess_protein with Sertoli cell development, anatomy_protein_present with medulla oblongata, anatomy_protein_present with medulla oblongata. TLE5 has relations: protein_protein with GRN, protein_protein with GRN, protein_protein with GRB2, protein_protein with GRB2. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. Embryonic Stem Cell defined as following: Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.. teratomas defined as following: A true neoplasm composed of a number of different types of tissue, none of which is native to the area in which it occurs. It is composed of tissues that are derived from three germinal layers, the endoderm, mesoderm, and ectoderm. They are classified histologically as mature (benign) or immature (malignant). (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1642). multifunctional protein defined as following: This gene is involved in fatty acid oxidation..", "label": "no"} {"id": "converted_2372", "sentence1": "Is there any linear-time and linear-space algorithm for the computation of avoided words in biological sequences?", "sentence2": "The systematic search for avoided words is particularly useful for biological sequence analysis. We present a linear-time and linear-space algorithm for the computation of avoided words of lengthkin a given sequencex. We suggest a modification to this algorithm so that it computes all avoided words ofx, irrespective of their length, within the same time complexity. We also present combinatorial results with regards to avoided words and absent words., We present a linear-time and linear-space algorithm for the computation of avoided words of lengthRespond with exceptions, completions and modifications or revisions done before completion
. expected defined as following: Considered likely or probable; anticipated..", "label": "yes"} {"id": "converted_3510", "sentence1": "Are there interactions between short and long noncoding RNAs?", "sentence2": "It is now evident that noncoding RNAs play key roles in regulatory networks determining cell fate and behavior, in a myriad of different conditions, and across all species. Among these noncoding RNAs are short RNAs, such as MicroRNAs, snoRNAs, and Piwi-interacting RNAs, and the functions of those are relatively well understood. Other noncoding RNAs are longer, and their modes of action and functions are also increasingly explored and deciphered. Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions. LncRNAs serve as precursors for many types of small RNAs and, therefore, the pathways for small RNA biogenesis can impinge upon the fate of lncRNAs. In addition, lncRNA expression can be repressed by small RNAs, and lncRNAs can affect small RNA activity and abundance through competition for binding or by triggering small RNA degradation. Here, I review the known types of interactions between small and long RNAs, discuss their outcomes, and bring representative examples from studies in mammals., Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions., Short RNAs and long noncoding RNAs (lncRNAs) interact with each other with reciprocal consequences for their fates and functions.[SEP]Relations: long noncoding RNA binding has relations: molfunc_protein with MIR384, molfunc_protein with MIR384. PIWI-interacting RNA (piRNA) biogenesis has relations: pathway_protein with HSP90AA1, pathway_protein with HSP90AA1, pathway_protein with TDRD9, pathway_protein with TDRD9, pathway_protein with TDRD6, pathway_protein with TDRD6, pathway_protein with MAEL, pathway_protein with MAEL. Definitions: mammals defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. MicroRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. lncRNA defined as following: A molecule of RNA 200-17000 nucleotides in length that is transcribed by non-protein coding areas of DNA. These ribonucleotides may play a role in a variety of biological processes.. Piwi-interacting RNAs defined as following: Single-stranded RNA molecules that are expressed in animal cells and form complexes with Piwi proteins. They are involved in transcriptional gene silencing..", "label": "yes"} {"id": "converted_4250", "sentence1": "Is Ozanimod effective for Ulcerative Colitis?", "sentence2": "Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis., CONCLUSIONS: Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis., CONCLUSIONS: There was a high rate of continued study participation and long-term benefit with ozanimod HCl 1 mg daily based on clinical, histological and biomarker measures in patients with moderately to severely active UC in the TOUCHSTONE OLE. [NCT02531126]., Ozanimod: A First-in-Class Sphingosine 1-Phosphate Receptor Modulator for the Treatment of Ulcerative Colitis., CONCLUSION: Ozanimod is another option in the growing arsenal of UC treatment., RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Ozanimod is the first sphingosine 1-phosphate modulator to be approved for UC and is administered orally. Its efficacy profile is comparable with other UC medications., Compared with placebo, ozanimod led to clinical remission in a significantly higher proportion of patients in both the induction and maintenance phase. Additionally, for secondary end points of clinical response, endoscopic improvement, corticosteroid-free remission, and mucosal healing, ozanimod performed significantly better than placebo. , Ozanimod interferes with migrations of activated T cells to the site of inflammation and is a promising drug for the UC treatment.Key words: Crohns disease - mongersen - monoclonal antibodies - ozanimod - tofacitinib - ulcerative colitis., SIONS: Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. (Fund, The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. , Ozanimod (RPC1063) is a specific and potent small molecule modulator of the sphingosine 1-phosphate receptor 1 (S1PR1) and receptor 5 (S1PR5), which has shown therapeutic benefit in clinical trials of relapsing multiple sclerosis and ulcerative colitis. Ozan, SIONS: Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. (Fun, SIONS: In this preliminary trial, ozanimod at a daily dose of 1 mg resulted in a slightly higher rate of clinical remission of ulcerative colitis than placebo. The [SEP]Relations: ulcerative colitis (disease) has relations: contraindication with Benzthiazide, contraindication with Benzthiazide, contraindication with Icosapent, contraindication with Icosapent, contraindication with Polythiazide, contraindication with Polythiazide, contraindication with Chlorothiazide, contraindication with Chlorothiazide, contraindication with Trolnitrate, contraindication with Trolnitrate. Definitions: agonist defined as following: An agent that has affinity for a receptor and intrinsic activity at that receptor.. drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. Ulcerative Colitis defined as following: Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.. S1P1 defined as following: Sphingosine 1-phosphate receptor 1 (382 aa, ~43 kDa) is encoded by the human S1PR1 gene. This protein plays a role in phospholipid binding.. T cells defined as following: A subset of therapeutic autologous T-lymphocytes that express a T-cell receptor (TCR) composed of one gamma chain and one delta chain, with potential immunomodulating and antineoplastic activities. Upon administration of the therapeutic gamma delta T-lymphocytes, these cells secrete interferon-gamma (IFN-g), and exert direct killing of tumor cells. In addition, these cells activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response against tumor cells. Gamma delta T-lymphocytes play a key role in the activation of the immune system and do not require major histocompatibility complex (MHC)-mediated antigen presentation to exert their cytotoxic effect.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. multiple sclerosis defined as following: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903). ozanimod defined as following: An orally bioavailable sphingosine-1-phosphate (S1P) receptors 1 (S1PR1, S1P1) and 5 (S1PR5, S1P5) modulator, with potential anti-inflammatory and immunomodulating activities. Upon oral administration, ozanimod selectively targets and binds to S1PR1 on lymphocytes and induces S1PR1 internalization and degradation. This results in the sequestration of lymphocytes in lymph nodes. By preventing egress of lymphocytes, ozanimod reduces both the amount of circulating peripheral lymphocytes and the infiltration of lymphocytes into target tissues. This prevents a lymphocyte-mediated immune response and may reduce inflammation. S1PR1, a G-protein coupled receptor, plays a key role in lymphocyte migration from lymphoid tissues. Modulation of S1PR5 by ozanimod may be neuroprotective.. Crohns disease defined as following: A chronic transmural inflammation that may involve any part of the DIGESTIVE TRACT from MOUTH to ANUS, mostly found in the ILEUM, the CECUM, and the COLON. In Crohn disease, the inflammation, extending through the intestinal wall from the MUCOSA to the serosa, is characteristically asymmetric and segmental. Epithelioid GRANULOMAS may be seen in some patients.. sphingosine 1-phosphate receptor 1 defined as following: A subfamily of lysophospholipid receptors with specificity for sphingosine-1-phosphate (e.g., FINGOLIMOD), sphinganine 1-phosphate, 4-hydroxysphinganine 1-phosphate.. HCl defined as following: A neoplastic disease of the lymphoreticular cells which is considered to be a rare type of chronic leukemia; it is characterized by an insidious onset, splenomegaly, anemia, granulocytopenia, thrombocytopenia, little or no lymphadenopathy, and the presence of \"hairy\" or \"flagellated\" cells in the blood and bone marrow..", "label": "yes"} {"id": "converted_711", "sentence1": "Do proton pump inhibitors affect thyroxine absorption?", "sentence2": "Proton-pump inhibitors, antacids and a long list of drugs may decrease thyroxine absorption, Many commonly used drugs, such as bile acid sequestrants, ferrous sulphate, sucralfate, calcium carbonate, aluminium-containing antacids, phosphate binders, raloxifene and proton-pump inhibitors, have also been shown to interfere with the absorption of levothyroxine., Pantoprazole did not influence endocrine function in healthy male volunteers during short-term treatment., PPIs should be added to the list of medications affecting the level of thyroid hormone in patients with hypothyroidism treated with LT4 replacement. Patients with hypothyroidism and normal TSH values during LT4 replacement therapy may need additional thyroid function testing after treatment with PPIs and may need adjustment of their LT4 dose.[SEP]Relations: Pantoprazole has relations: drug_effect with Thrombophlebitis, drug_effect with Thrombophlebitis, drug_effect with Nocturia, drug_effect with Nocturia, drug_effect with Thrombocytopenia, drug_effect with Thrombocytopenia, drug_effect with Albuminuria, drug_effect with Albuminuria. Raloxifene has relations: drug_effect with Thrombocytopenia, drug_effect with Thrombocytopenia. Definitions: calcium carbonate defined as following: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement.. levothyroxine defined as following: The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.. sucralfate defined as following: A basic aluminum complex of sulfated sucrose.. raloxifene defined as following: A selective benzothiophene estrogen receptor modulator (SERM). Raloxifene binds to estrogen receptors (ER) as a mixed estrogen agonist/antagonist; it displays both an ER-alpha-selective partial agonist/antagonist effect and a pure ER-beta-selective antagonist effect. This agent functions as an estrogen agonist in some tissues (bones, lipid metabolism) and as an estrogen antagonist in others (endometrium and breasts), with the potential for producing some of estrogen's beneficial effects without producing its adverse effects. (NCI04). antacids defined as following: Substances that counteract or neutralize acidity of the GASTROINTESTINAL TRACT.. thyroid hormone defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs.. Pantoprazole defined as following: 2-pyridinylmethylsulfinylbenzimidazole proton pump inhibitor that is used in the treatment of GASTROESOPHAGEAL REFLUX and PEPTIC ULCER.. hypothyroidism defined as following: A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction.. ferrous sulphate defined as following: A sulfate salt of mineral iron formulated for oral administration and used as a dietary supplement, ferrous sulfate is absorbed in the stomach and small intestine and combines with apoferritin to form ferritin, which is stored in the liver, spleen, red bone marrow, and intestinal mucosa. Important in transport of oxygen by hemoglobin to the tissues, iron is also found in myoglobin, transferrin, and ferritin, and is a component of many enzymes such as catalase, peroxidase, and cytochromes..", "label": "yes"} {"id": "converted_156", "sentence1": "Is the gene MAOA epigenetically modified by methylation?", "sentence2": "Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAO A enzyme in healthy men., We found significant interindividual differences in methylation status and methylation patterns of the core MAOA promoter. , In the present study, DNA methylation patterns in the MAOA regulatory and exon 1/intron 1 region were investigated for association with panic disorder with particular attention to possible effects of gender and environmental factors. , The present pilot data suggest a potential role of MAOA gene hypomethylation in the pathogenesis of panic disorder particularly in female patients, possibly mediating a detrimental influence of negative life events. , The MAOA promoter was hypermethylated immediately upstream of the start codon in cholangiocarcinoma samples and cell lines but not in nonmalignant counterparts. , MAOA promoter methylation and susceptibility to carotid atherosclerosis: role of familial factors in a monozygotic twin sample., Because twins reared together share early life experience, which may leave a long-lasting epigenetic mark, aberrant MAOA methylation may represent an early biomarker for unhealthy familial environment., Effects of MAOA promoter methylation on susceptibility to paranoid schizophrenia., In conclusion, abnormalities of DNA methylation at the MAOA promoter may be associated with schizophrenia in males., In our study we analyzed DNA methylation patterns of 14 neuropsychiatric genes (COMT, DAT1, GABRA1, GNB3, GRIN2B, HTR1B, HTR2A, 5-HTT, MAOA, MAOB, NOS1, NR3C1, TPH1 and TH). D, Our data suggest that aberrant epigenetic regulation of neuropsychiatric genes may contribute to the pathogenesis of BPD., We conclude that smoking reliably decreases MAOA methylation, but exact characterization of effects on level of methylation depend on genotype, smoking history, current smoking status, gender, and region of the promoter-associated CpG Island examined., Given that DNA methylation is linked to the regulation of gene expression, we hypothesized that epigenetic mechanisms factor into the MAOA expression, the extended MAOA regulatory region contains two CpG islands (CGIs), one of which overlaps with the canonical MAOA promoter and the other is located further upstream; both CGIs exhibit sensitivity to differential methylation., Identification and characterization of putative methylation targets in the MAOA locus using bioinformatic approaches., DNA methylation is a key epigenetic mechanism involved in the developmental regulation of gene expression. , MAOA methylation is associated with nicotine and alcohol dependence in women., In recent years, the role of epigenetic phenomenon, such as methylation, in mediating vulnerability to behavioral illness has become increasingly appreciated. One prominent locus at which epigenetic phenomena are thought to be in play is the monoamine oxidase A (MAOA) locus. , We conclude that methylation of MAOA may play a significant role in common psychiatric illness and that further examination of epigenetic processes at this locus is in order., Analysis of CpG methylation in the MAOA promoter region revealed substantial methylation in females but not in males., Therefore, allelic mRNA expression is affected by genetic and epigenetic events, both with the potential to modulate biogenic amine tone in the CNS.[SEP]Relations: Enzymatic degradation of Dopamine by monoamine oxidase has relations: pathway_protein with MAOA, pathway_protein with MAOA. monoamine oxidase activity has relations: molfunc_protein with MAOA, molfunc_protein with MAOA, molfunc_protein with MAOA, molfunc_protein with MAOA, molfunc_protein with MAOB, molfunc_protein with MAOB. central nervous system has relations: anatomy_protein_present with MAOA, anatomy_protein_present with MAOA. Definitions: HTR2A defined as following: HTR2A-C Allele is a variant form of 20-kb 3-exon human HTR2A Gene (GPCR1/5HT2 Family), which encodes Serotonin 5-HT-2A Receptor, a conserved integral membrane 5-HT/serotonin receptor protein involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production by association with G proteins that activate a PI-calcium second messenger system. 5-HT is a biogenic hormone that affects specific receptors as a neurotransmitter, hormone, or mitogen. HTR2A contains several polymorphic sites. Different alleles differ in the concentration of RNA and protein product of 5HTR2A. HTR2A-C Allele contains a single-nucleotide polymorphism (102 T>C) in an intron and is expressed at a lower level than the 102 C>T allele.. GRIN2B defined as following: This gene plays a role in both neurotransmitter binding and ion transport.. HTR1B defined as following: 5-hydroxytryptamine receptor 1B (390 aa, ~44 kDa) is encoded by the human HTR1B gene. This protein is involved in serotonin binding and regulation of the release of serotonin, dopamine and acetylcholine in the brain.. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. TPH1 defined as following: Tryptophan 5-hydroxylase 1 (444 aa, ~51 kDa) is encoded by the human TPH1 gene. This protein plays a role in the metabolism of tryptophan.. TH defined as following: Tyrosine 3-monooxygenase (528 aa, ~59 kDa) is encoded by the human TH gene. This protein plays a role in the synthesis of dopamine from L-tyrosine.. panic disorder defined as following: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait.. MAOB defined as following: Amine oxidase [flavin-containing] B (520 aa, ~59 kDa) is encoded by the human MAOB gene. This protein is involved in the deamination of amines.. monoamine oxidase A defined as following: This gene is involved in the metabolism of neuroactive and vasoactive amines.. behavioral illness defined as following: Coordinate set of non-specific behavioral responses to non-psychiatric illness. These may include loss of APPETITE or LIBIDO; disinterest in ACTIVITIES OF DAILY LIVING; or withdrawal from social interaction.. promoter defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. region defined as following: The continents and countries situated on those continents; the UNITED STATES and each of the constituent states arranged by region; CANADA and each of its provinces; AUSTRALIA and each of its states; the major bodies of water and major islands on both hemispheres; and selected major cities.. GNB3 defined as following: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 (340 aa, ~37 kDa) is encoded by the human GNB3 gene. This protein plays a role in the mediation of G protein-coupled receptor signaling.. COMT defined as following: Enzyme that catalyzes the movement of a methyl group from S-adenosylmethionone to a catechol or a catecholamine.. cell lines defined as following: Established cell cultures that have the potential to propagate indefinitely.. nicotine defined as following: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.. BPD defined as following: A personality disorder marked by a pattern of instability of interpersonal relationships, self-image, and affects, and marked impulsivity beginning by early adulthood and present in a variety of contexts. (DSM-IV). psychiatric illness defined as following: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.. DAT1 defined as following: Human SLC6A3 wild-type allele is located in the vicinity of 5p15.3 and is approximately 53 kb in length. This allele, which encodes sodium-dependent dopamine transporter protein, is involved in sodium-dependent internalization of dopamine. Mutation of the gene is associated with infantile Parkinsonism-dystonia.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. NR3C1 defined as following: Human NR3C1 wild-type allele is located in the vicinity of 5q31.3 and is approximately 125 kb in length. This allele, which encodes glucocorticoid receptor protein, is involved in transcriptional regulation that affects a variety of processes such as blood glucose concentration, protein/fat metabolism, inflammatory responses, cellular proliferation, and differentiation. Mutations in the gene are a primary cause of glucocorticoid resistance, or cortisol resistance.. locus defined as following: The position of a gene or a chromosomal marker on a chromosome; also, a stretch of DNA at a particular place on a particular chromosome. The use of locus is sometimes restricted to mean regions of DNA that are expressed.. MAOA defined as following: Amine oxidase [flavin-containing] A (527 aa, ~60 kDa) is encoded by the human MAOA gene. This protein is involved in the deamination of neuroactive and vasoactive amines.. modified defined as following: The act of alteration or modification; changed or altered in form or character..", "label": "yes"} {"id": "converted_4608", "sentence1": "Is Benralizumab effective for Chronic Spontaneous Urticaria?", "sentence2": "Finally, treatments aimed at reducing eosinophil accumulation and activation, such as the anti-IL-5 antibodies mepolizumab, reslizumab, and benralizumab, have been reported to reduce CSU symptoms. , The treatments that are under clinical trials for CSU are anti-IgE treatments such as ligelizumab, molecules targeting intracellular signaling pathways such as spleen tyrosine kinase inhibitors, surface inhibitory molecules such as siglec-8, anti-IL-1s such as canakinumab, Bruton kinase (BTK) inhibitors such as GDC-0853 and anti-IL-5s such as benralizumab and mepolizumab., f-label use of dupilumab, reslizumab, mepolizumab, and benralizumab can be effective in CU. Ligel, Finally, treatments aimed at reducing eosinophil accumulation and activation, such as the anti-IL-5 antibodies mepolizumab, reslizumab, and benralizumab, have been reported to reduce CSU symptoms., ments aimed at reducing eosinophil accumulation and activation, such as the anti-IL-5 antibodies mepolizumab, reslizumab, and benralizumab, have been reported to reduce CSU symptoms. Clearly, a new pi, ormation on the effects of the off-label use, in CSU, of biologics licensed for the treatment of other diseases, including dupilumab, benralizumab, mepolizumab, reslizumab, and secukinumab. Finally, we discuss, , B cells, T cells and eosinophils. The treatments that are under clinical trials for CSU are anti-IgE treatments such as ligelizumab, molecules targeting intracellular signaling pathways such as spleen tyrosine kinase inhibitors, surface inhibitory molecules such as siglec-8, anti-IL-1s such as canakinumab, Bruton kinase (BTK) inhibitors such as GDC-0853 and anti-IL-5s such as benralizumab and mepolizumab.SUMMARY: The ongoing clinical trials on new targets of treatment hold new hopes not only for a better care of the disease but also a better understan[SEP]Relations: Benralizumab has relations: drug_drug with Urelumab, drug_drug with Urelumab, drug_drug with Evinacumab, drug_drug with Evinacumab, drug_drug with Fremanezumab, drug_drug with Fremanezumab, drug_drug with Adecatumumab, drug_drug with Adecatumumab, drug_drug with Galcanezumab, drug_drug with Galcanezumab. Definitions: T cells defined as following: A subset of therapeutic autologous T-lymphocytes that express a T-cell receptor (TCR) composed of one gamma chain and one delta chain, with potential immunomodulating and antineoplastic activities. Upon administration of the therapeutic gamma delta T-lymphocytes, these cells secrete interferon-gamma (IFN-g), and exert direct killing of tumor cells. In addition, these cells activate the immune system to exert a cytotoxic T-lymphocyte (CTL) response against tumor cells. Gamma delta T-lymphocytes play a key role in the activation of the immune system and do not require major histocompatibility complex (MHC)-mediated antigen presentation to exert their cytotoxic effect.. CSU defined as following: Urticaria characterized by spontaneously recurring hives for 6 weeks or longer. [PMID:25807072]. canakinumab defined as following: A recombinant monoclonal antibody targeting human interleukin-1 beta (IL-1b), with anti-inflammatory and immunomodulating activities. Canakinumab binds IL-1b and prevents the binding of IL-1b to the IL-1 receptor and inhibits IL-1b-mediated signaling. This may suppress inflammatory responses mediated by IL-1b. IL-1b, a proinflammatory cytokine, plays a key role in inflammation.. eosinophil defined as following: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin.. molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. tyrosine kinase inhibitors defined as following: Protein kinase inhibitors that inhibit TYROSINE PROTEIN KINASES.. benralizumab defined as following: An afucosylated, humanized monoclonal antibody against the alpha chain of the interleukin-5 receptor (IL-5Ra), with potential anti-asthmatic activity. Upon administration, benralizumab binds to IL-5Ra and elicits an antibody-directed cell cytotoxicity (ADCC) against IL-5Ra-expressing cells. This induces apoptosis in IL-5Ra-expressing cells and may reduce asthmatic episodes. IL-5Ra, expressed on both eosinophils and basophils, plays a key role in asthma.. B cells defined as following: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.. mepolizumab defined as following: A humanized immunoglobulin G1 (IgG1) monoclonal antibody directed against interleukin-5 (IL-5) with anti-asthmatic and potential immunosuppressive activity. Upon subcutaneous administration, mepolizumab selectively binds to IL-5, preventing it from associating with interleukin-5 receptor subunit alpha (IL5RA) on the surface of eosinophils and their progenitors. IL-5 plays a role in the regulation of eosinophil development from hematopoietic progenitors as well as eosinophil maturation, differentiation, mobilization, activation, and survival. IL-5 also play a role in the pathogenesis of some phenotypes of hypereosinophilic syndrome (HES).. secukinumab defined as following: A recombinant human immunoglobulin G1 (IgG1) monoclonal antibody against the pro-inflammatory cytokine interleukin 17A (IL-17A; IL-17), with potential anti-inflammatory activity. Upon subcutaneous administration, secukinumab selectively targets and binds to IL-17A, thereby neutralizing the IL-17A protein. This prevents binding of IL-17A to the IL-17 receptor (IL-17R), and inhibits IL-17A/IL-17R-mediated signaling and inflammation mediated by this pathway. IL-17A is mainly produced by inflammatory T helper 17 cells (Th17), and certain lymphocytes. IL-17A production is upregulated in many immune-mediated inflammatory diseases and plays a key role in the development of inflammation and the immune response..", "label": "yes"} {"id": "converted_4499", "sentence1": "Does Amblyopia affect the eye?", "sentence2": "The main goal of our study is to assess the effect of transcranial magnetic stimulation, specifically theta burst stimulation (TBS), in a group of amblyopic volunteers measuring several visual parameters: visual acuity, suppressive imbalance, and stereoacuity, This study was undertaken to determine if optometrists in Ghana screen, diagnose and manage paediatric ocular conditions (for example, strabismus, amblyopia), and further assessed if optometrists in Ghana have the requisite paediatric instrumentation in their practices., Many bilateral amblyopia patients have asymmetric visual acuity (VA)., LTS: In patients with persistent amblyopia and in those with recovered amblyopia, the affected eyes were significantly more hyperopic than the fellow eyes. The, e RNFLT was compared between the affected and fellow eyes in patients with persistent amblyopia and in those with recovered amblyopia, and between the amblyopic eyes of patients with persistent amblyopia and the previously amblyopic eyes of patients with recovered amblyopia.RE, We compared the optic nerve head topography and retinal nerve fiber layer (RNFL) thickness of the strabismic and anisometropic amblyopic eyes with the normal fellow eyes and age-matched controls and concluded that, although amblyopia is a functional visual loss, RNFL thickness and optic nerve head topographic changes in strabismic and anisometropic amblyopic eyes may be affected by amblyopia., ODS: Four consecutive infants between 7 and 19 months of age with unilateral periocular vascular lesions that intermittently obstructed vision in the affected eye and no clinical evidence of amblyopia were evaluated. No , Histologic study of the LGNs from a patient with ophthalmologically confirmed anisometropic amblyopia shows a decrease of cell sizes in the parvocellular layers innervated by the amblyopic eye., S: Neutral density filters affect eyes with strabismic amblyopia differently than they do non-amblyopic eyes. A signifi, Together with recent advances in our theoretical understanding of amblyopia and technological advances in amblyopia treatment, we anticipate improved visual outcomes for children affected by this very common eye condition., OBJECTIVE: Amblyopia or lazy eye is a common visual problem affecting children that cannot correct with lenses., Experimental amblyopia in animal models causes a reduction of cell sizes in lateral geniculate nucleus (LGN) laminae connected with the amblyopic eye., Amblyopia cannot be cured by treating the cause alone; the weaker eye must be made stronger in order to see normally., To correct amblyopia, a child must be made to use the weak eye., Similarly, decreased activation of the LGN as well as the visual cortex by the affected eye was demonstrated in the patient with anisometropic amblyopia., Amblyopia is defined as a loss of letter recognition visual acuity in the affected eye; however, studies in both nonhuman primates and man have shown that other important aspects of vision, including color, motion, and contour perception, are also abnormal. The, Amblyopia is a developmental disorder that affects the spatial vision of one or both eyes in the absence of an obvious organic cause; it is associated with a history of abnormal visual experience during childhood, Amblyopia is defined as the reduction of best-corrected visual acuity of one or both eyes caused by conditions that affect normal visual development, Amblyopia is a reduced best-corrected visual acuity of one or both eyes that cannot be attributed to a structural abnormality; it is a functional reduction in the vision of an eye caused by disuse during a critical period of visual development, Amblyopia is defined as reduced and uncorrectable vision in a structurally normal eye, Amblyopia or \"lazy eye\" represents a disorder of the visual system characterized by poor vision in an eye that is otherwise physically normal. , Amblyopia is a common visual disorder that results in a spatial acuity deficit in the affected eye, Amblyopia is a common deficit in spatial vision that could be based on either unreliable local estimates of image structure, irregularities in global image integration or a combination of errors at both these stages., Amblyopia is a disorder of visual acuity in one eye, thought to arise from suppression by the other eye during development of the visual cortex., Amblyopia is characterised by decrease in vision in one or both eyes as a result of processing defect in the visual pathways of the brain, Amblyopia is defined as a loss of letter recognition visual acuity in the affected eye; however, studies in both nonhuman primates and man have shown that other important aspects of vision, including color, motion, and contour perception, are also abnormal, Amblyopia, commonly known as \"lazy eye,\" is a frequent but preventable cause of decreased vision, Here, we consider four explanations that may account for decreased fellow eye sensitivity: the fellow eye is adversely impacted by treatment for amblyopia; the maturation of the fellow eye is delayed by amblyopia; fellow eye sensitivity is impacted for visual functions that rely on binocular cortex; and fellow eye deficits reflect an adaptive mechanism that works to equalize the sensitivity of the two eyes, Therefore, the aim of this review paper is to provide a comprehensive review of current knowledge about the effects of amblyopia on eye movements, upper limb reaching and grasping movements, as well as balance and gait, Atropine occlusion in the treatment of strabismic amblyopia and its effect upon the non-amblyopic eye., Amblyopia is the most common cause of monocular visual impairment in children, with a prevalence of 2-3%, Amblyopia is a neurodevelopmental disorder of the visual system, as a result of discordant visual experience during infancy or early childhood, By its nature, however, amblyopia has an adverse effect on the development of a binocular visual system and the interactions between signals from two eyes., Unilateral Amblyopia Affects Two Eyes: Fellow Eye Deficits in Amblyopia., PURPOSE: Impairment of spatiotemporal visual processing is the hallmark of amblyopia, but its effects on eye movements during visuomotor tasks have rarely been, Amblyopia is defined as a loss of letter recognition visual acuity in the affected eye; however, studies in both nonhuman primates and man have shown that other important aspects of vision, including color, motion, and contour perception, are also abnormal., Further research targeted at exploring fellow eye deficits in amblyopia will provide us with a broader understanding of normal visual development and how amblyopia impacts the developing visual system., While these fellow eye deficits have been noted, no overarching theory has been proposed to describe why and under what conditions the fellow eye is impacted by amblyopia., Here, we consider four explanations that may account for decreased fellow eye sensitivity: the fellow eye is adversely impacted by treatment for amblyopia; the maturation of the fellow eye is delayed by amblyopia; fellow eye sensitivity is impacted for visual functions that rely on binocular cortex; and fellow eye deficits reflect an adaptive mechanism that works to equalize the sensitivity of the two eyes., In anisometropes, the amblyopic eye influenced a relatively small proportion of cortical neurons; in strabismics, the influence of the two eyes was more nearly equal., studied. Here the authors investigate how visual deficits in anisometropic amblyopia affect saccadic eye movements.METHODS: Thirteen patients with anisometropic amblyopia and 13 control subj, Unilateral amblyopia is a visual disorder that arises after selective disruption of visual input to one eye during critical periods of development., Amblyopia is a developmental disorder resulting in poor vision in one eye., In the clinic, amblyopia is understood as poor visual acuity in an eye that was deprived of pattern vision early in life., Ocular misalignment or unilateral blur often causes amblyopia, a disorder that has become a standard for understanding developmental plasticity., Amblyopia is a developmental disorder of pattern vision., amblyopia are associated with poor PS. PS of amblyopic and fellow eyes is differentially , The contrast sensitivity function of both eyes of subjects with functional amblyopia has been measured. A clinically significant difference was found between the amblyopic and the normal eye., t appears that the functionally amblyopic eye takes more information from the peripheral parts of the stimulus than does the normal eye, Previous studies focused on the differences between amblyopic patients and normal controls without evaluating amblyopic eyes after patching. To evaluate differences in the superficial vascular density of amblyopic eyes, normal eyes, and amblyopic eyes reaching normal BCVA after patch therapy,[SEP]Relations: vision disorder has relations: disease_disease with amblyopia (disease), disease_disease with amblyopia (disease). ametropic amblyopia has relations: disease_disease with amblyopia (disease), disease_disease with amblyopia (disease), disease_disease with amblyopia (disease), disease_disease with amblyopia (disease). suppression amblyopia has relations: disease_disease with toxic amblyopia, disease_disease with toxic amblyopia, disease_disease with amblyopia (disease), disease_disease with amblyopia (disease). Definitions: visual disorder defined as following: Visual impairments limiting one or more of the basic functions of the eye: visual acuity, dark adaptation, color vision, or peripheral vision. These may result from EYE DISEASES; OPTIC NERVE DISEASES; VISUAL PATHWAY diseases; OCCIPITAL LOBE diseases; OCULAR MOTILITY DISORDERS; and other conditions (From Newell, Ophthalmology: Principles and Concepts, 7th ed, p132).. man defined as following: Members of the species Homo sapiens.. Amblyopia defined as following: A nonspecific term referring to impaired vision. Major subcategories include stimulus deprivation-induced amblyopia and toxic amblyopia. Stimulus deprivation-induced amblyopia is a developmental disorder of the visual cortex. A discrepancy between visual information received by the visual cortex from each eye results in abnormal cortical development. STRABISMUS and REFRACTIVE ERRORS may cause this condition. Toxic amblyopia is a disorder of the OPTIC NERVE which is associated with ALCOHOLISM, tobacco SMOKING, and other toxins and as an adverse effect of the use of some medications.. Eyes defined as following: The organ of sight constituting a pair of globular organs made up of a three-layered roughly spherical structure specialized for receiving and responding to light.. neurodevelopmental disorder defined as following: A childhood disorder that has a neurological basis and manifests as a developmental disability..", "label": "yes"} {"id": "converted_4240", "sentence1": "Is Cabotegravir effective for HIV prevention?", "sentence2": "A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV., PURPOSE OF REVIEW: Cabotegravir (CAB) and rilpivirine (RPV) is the first long-acting injectable antiretroviral therapy (ART) option approved for virologically suppressed adults with HIV-1. In addition, long-acting CAB is a promising agent for HIV preexposure prophylaxis (PrEP). , SUMMARY: Clinical trial results support the use of long-acting CAB for HIV PrEP and long-acting CAB and RPV as a switch strategy for adults with HIV-1 who are first virologically suppressed with oral ART. , OBJECTIVE: We had previously shown that long-acting cabotegravir (CAB-LA) injections fully protected macaques from vaginal simian HIV (SHIV) infection., The Potential Impact of Long-Acting Cabotegravir for HIV Prevention in South Africa: A Mathematical Modeling Study., Long-acting cabotegravir (CAB LA) is a potential new injectable formulation for human immunodeficiency virus (HIV) PrEP being tested in phase III trials., Design and Testing of a Cabotegravir Implant for HIV Prevention., Cabotegravir and rilpivirine long-acting injectable antiretroviral therapy for the treatment of HIV-1 infection brings promise of a new mode of delivery and potential solutions to some problems of oral therapy, but also new challenges and unanswered questions., Cabotegravir is an investigational integrase inhibitor in development for the treatment and pre-exposure prophylaxis of HIV-1 infection., Bictegravir, cabotegravir, dolutegravir, elvitegravir, and raltegravir are members of the latest class of antiretrovirals available to treat human immunodeficiency virus (HIV) infection, the integrase strand transfer inhibitors., PURPOSE OF REVIEW: Long-acting cabotegravir may provide a novel therapeutic option for both the treatment and prevention of HIV-1 infection that does not necessitate adherence, Long-acting injectable cabotegravir for the prevention of HIV infection, BACKGROUND: The HIV Prevention Trials Network (HPTN) 083 trial demonstrated that long-acting cabotegravir (CAB-LA) was more effective than tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) in preventing human immunodeficiency virus (HIV) in cisgender men and transgender women who have sex with, Areas covered: Here, we review trials of cabotegravir (CAB) as treatment of HIV-1 infection and its potential use as pre-exposure prophylaxis (PrEP) in high risk individuals, including issues around oral lead in and potential resistance emergence. Exper, frequent dosing. This review focuses on the potential benefits and considerations for the study and use of 2 long-acting injectable agents, cabotegravir (GSK1265744LA, CAB LA) and rilpivirine (TMC278LA, RPV LA), for use as chemoprophylaxis for HIV , An evaluation of cabotegravir for HIV treatment and prevention., Cabotegravir long-acting for HIV-1 prevention., Our findings suggest that cabotegravir should be evaluated in clinical trials as a potential option for antiretroviral therapy and preexposure prophylaxis in HIV-2-prevalent settings., Profile of cabotegravir and its potential in the treatment and prevention of HIV-1 infection: evidence to date., Long-Acting Cabotegravir for HIV/AIDS Prophylaxis., Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women., Cabotegravir is a novel human immunodeficiency virus integrase enzyme inhibitor used for prevention and treatment of HIV infection., PURPOSE OF REVIEW: Long-acting cabotegravir may provide a novel therapeutic option for both the treatment and prevention of HIV-1 infection that does not necessitate adherence , Cabotegravir in the treatment and prevention of Human Immunodeficiency Virus-1., Cabotegravir: its potential for antiretroviral therapy and preexposure prophylaxis., Satisfaction and acceptability of cabotegravir long-acting injectable suspension for prevention of HIV: Patient perspectives from the ECLAIR trial.[SEP]Relations: Rilpivirine has relations: contraindication with chronic hepatitis B virus infection, contraindication with chronic hepatitis B virus infection, drug_drug with Cabazitaxel, drug_drug with Cabazitaxel, drug_drug with Paritaprevir, drug_drug with Paritaprevir. Raltegravir has relations: drug_drug with Pibrentasvir, drug_drug with Pibrentasvir, drug_drug with Paritaprevir, drug_drug with Paritaprevir. Definitions: integrase inhibitor defined as following: An agent that blocks the activity of the human immunodeficiency virus (HIV) integrase enzyme.. PrEP defined as following:PrEP and PEP are medicines to prevent HIV. Each type is used in a different situation:
PrEP is for people without HIV who are at very high risk for getting it. This includes:
Gay/bisexual men who
Heterosexual men and women who
People who inject drugs and
If you have a partner who is HIV-positive and are considering getting pregnant, talk to your health care provider about PrEP. Taking it may help protect you and your baby from getting HIV infection while you try to get pregnant, during pregnancy, or while breastfeeding.
PrEP is very effective when you take it every day. It reduces the risk of getting HIV from sex by more than 90%. In people who inject drugs, it reduces the risk of HIV by more than 70%. PrEP is much less effective if you do not take it consistently.
PrEP does not protect against other STDs, so you should still use latex condoms every time you have sex. If your or your partner is allergic to latex, you can use polyurethane condoms.
You must have an HIV test every 3 months while taking PrEP, so you'll have regular follow-up visits with your health care provider. If you are having trouble taking PrEP every day or if you want to stop taking PrEP, talk to your health care provider.
Some people taking PrEP may have side effects, like nausea. The side effects are usually not serious and often get better over time. If you are taking PrEP, tell your health care provider if you have a side effect that bothers you or that does not go away.
If you are HIV-negative and you think you may have been recently exposed to HIV, contact your health care provider immediately or go to an emergency room right away.
You may be prescribed PEP if you are HIV negative or don't know your HIV status, and in the last 72 hours you
Your health care provider or emergency room doctor will help to decide whether PEP is right for you.
PEP may also be given to a health care worker after a possible exposure to HIV at work, for example, from a needlestick injury.
PEP must be started within 72 hours (3 days) after a possible exposure to HIV. The sooner you start it, the better; every hour counts.
You need to take the PEP medicines every day for 28 days. You will have to see your health care provider at certain times during and after taking the PEP, so you can have an HIV screening test and other testing.
Some people taking PEP may have side effects, like nausea. The side effects are usually not serious and often get better over time. If you are taking PEP, tell your health care provider if you have a side effect that bothers you or that does not go away.
PEP medicines may also interact with other medicines that a person is taking (called a drug interaction). So it's important to tell your health care provider about any other medicines that you take.
PEP is only for emergency situations. It is not the right choice for people who may be exposed to HIV frequently - for example, if you often have sex without a condom with a partner who is HIV-positive. In that case, you should talk to your health care provider about whether PrEP (pre-exposure prophylaxis) would be right for you.
. LA defined as following: Passive agglutination tests in which antigen is adsorbed onto latex particles which then clump in the presence of antibody specific for the adsorbed antigen. (From Stedman, 26th ed). rilpivirine defined as following: A second-generation non-nucleoside reverse transcriptase inhibitor. Rilpivirine is a diarylpyrimidine.. CAB defined as following: Carbonic anhydrase 1 (261 aa, ~29 kDa) is encoded by the human CA1 gene. This protein plays a role in carbon dioxide metabolism by erythrocytes.. raltegravir defined as following: A small molecule with activity against human immunodeficiency virus (HIV). Raltegravir is an integrase inhibitor that blocks the integration of the viral genome into the host DNA, a critical step in the pathogenesis of HIV.. macaques defined as following: A genus of the subfamily CERCOPITHECINAE, family CERCOPITHECIDAE, consisting of 16 species inhabiting forests of Africa, Asia, and the islands of Borneo, Philippines, and Celebes.. HIV defined as following: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS)..", "label": "yes"} {"id": "converted_3937", "sentence1": "Are mucins glycosylated proteins?", "sentence2": "Many members of the mucin family are evolutionarily conserved and are often aberrantly expressed and glycosylated in various benign and malignant pathologies leading to tumor invasion, metastasis, and immune evasion., Mucin is a glycoprotein that is the primary component of the mucus overlaying the epithelial tissues. , Mucin-type O-linked glycosylation[SEP]Relations: Protein S human has relations: drug_drug with Glycocholic acid, drug_drug with Glycocholic acid, drug_drug with Mitomycin, drug_drug with Mitomycin, drug_drug with Cephaloglycin, drug_drug with Cephaloglycin, drug_drug with Azithromycin, drug_drug with Azithromycin, drug_drug with Erythromycin, drug_drug with Erythromycin. Definitions: Mucin defined as following: Mucin-1 (1255 aa, ~122 kDa) is encoded by the human MUC1 gene. This protein plays a role in both signaling and cell adhesion.. epithelial tissues defined as following: The layers of EPITHELIAL CELLS which cover the inner and outer surfaces of the cutaneous, mucus, and serous tissues and glands of the body..", "label": "yes"} {"id": "converted_3760", "sentence1": "Are bacteria in the genus Clostridium facultative anaerobes?", "sentence2": "strict anaerobe Clostridium acetobutylicum, Clostridia belong to those bacteria which are considered as obligate anaerobe, e.g. oxygen is harmful or lethal to these bacteria., We report here the closed genome of Clostridium pasteurianum ATCC 6013, a saccharolytic, nitrogen-fixing, and spore-forming Gram-positive obligate anaerobe, Clostridium pasteurianum BB, a saccharolytic and spore-forming obligate anaerobe, Clostridium difficile is a spore-forming obligate anaerobe that is a leading cause of healthcare-associated infections, However, the discovery of antimicrobials has been biased towards aerobes and facultative anaerobes, and strict anaerobes such as Clostridium spp., Clostridium is a large genus of obligate anaerobes belonging to the Firmicutes phylum of bacteria, most of which have a Gram-positive cell wall structure., Such bacteria are either obligate anaerobic bacteria like Clostridium or Bifidobacterium or facultative anaerobic like Escherichia coli or Salmonella., Antimicrobial production by strictly anaerobic Clostridium spp.[SEP]Relations: anaerobic bacteria infectious disease has relations: disease_disease with Clostridium infectious disease, disease_disease with Clostridium infectious disease, disease_disease with infection caused by Bifidobacterium, disease_disease with infection caused by Bifidobacterium, disease_disease with Fusobacterium infectious disease, disease_disease with Fusobacterium infectious disease, disease_disease with Bacteroides infectious disease, disease_disease with Bacteroides infectious disease. Clostridium difficile colitis has relations: phenotype_phenotype with Unusual gastrointestinal infection, phenotype_phenotype with Unusual gastrointestinal infection. Definitions: anaerobe defined as following: Bacteria that can survive and grow in the complete, or nearly complete absence of oxygen.. healthcare-associated infections defined as following: Any infection which a patient contracts in a health-care institution.. Firmicutes defined as following: A taxonomic phylum within kingdom Bacteria consisting of mostly gram-positive bacteria with a low G+C ratio. The phylum is highly diverse in phenotypic characteristics.. antimicrobials defined as following: Generically, any agent that destroys microbes. However, usage of the term is increasingly being confined to agents that prevent or reduce the transmission of SEXUALLY TRANSMITTED DISEASES.. bacteria defined as following: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.. Clostridium difficile defined as following: A species of Clostridium that is the most significant cause of pseudomembranous colitis.. Escherichia coli defined as following: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc..", "label": "no"} {"id": "converted_443", "sentence1": "Can we detect DNA strand asymmetries using dinucleotide relative abundance \"genomic signatures\"?", "sentence2": "comparing the heterogeneities of bacterial genomes with respect to strand-independent first- and second-order features, (i) G + C content and (ii) dinucleotide relative abundance,, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes., dinucleotide relative abundance values (the genomic signature), The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome., The profile is computed from the base step \"odds ratios\" that compare dinucleotide frequencies to those expected under the assumption of stochastic equilibrium (thorough shuffling). , The genome signatures (dinucleotide relative abundance values), Early biochemical experiments measuring nearest neighbor frequencies established that the set of dinucleotide relative abundance values (dinucleotide biases) is a remarkably stable property of the DNA of an organism., the set of dinucleotide biases constitutes a 'genomic signature' that can discriminate sequences from different organisms., the set of dinucleotide odds ratio (relative abundance) values constitute a signature of each DNA genome, Dinucleotide relative abundance extremes: a genomic signature., The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome., Previously, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes., Comparisons within and between species sample sequences are based on the profile of dinucleotide relative abundance values (The profile is rho*XY = f*XY/f*Xf*Y for all XY, where f*X denotes the frequency of the nucleotide X and f*XY denotes the frequency of the dinucleotide XY, both computed from the sequence concatenated with its inverted complement)., Dinucleotide relative abundances (i.e., dinucleotide representations normalized by the component nucleotide frequencies) are consonant with respect to the leading and lagging strands[SEP]Relations: anatomical entity has relations: anatomy_anatomy with immaterial anatomical entity, anatomy_anatomy with immaterial anatomical entity, anatomy_anatomy with anatomical cluster, anatomy_anatomy with anatomical cluster, anatomy_anatomy with insect mouthpart, anatomy_anatomy with insect mouthpart, anatomy_anatomy with material anatomical entity, anatomy_anatomy with material anatomical entity. male organism has relations: anatomy_anatomy with multicellular organism, anatomy_anatomy with multicellular organism. Definitions: Dinucleotide defined as following: A group of compounds which consist of a nucleotide molecule to which an additional nucleoside is attached through the phosphate molecule(s). The nucleotide can contain any number of phosphates.. bacterial genomes defined as following: The genetic complement of a BACTERIA as represented in its DNA.. genome defined as following: Anatomical set of genes in all the chromosomes.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. organisms defined as following: A living entity.. dinucleotide defined as following: A group of compounds which consist of a nucleotide molecule to which an additional nucleoside is attached through the phosphate molecule(s). The nucleotide can contain any number of phosphates..", "label": "no"} {"id": "converted_4157", "sentence1": "Is metoprolol metabolized by CYP2D6?", "sentence2": "Among these beta-blockers atenolol is mainly eliminated by renal excretion, bisoprolol is in part excreted as parent compound via the renal route (50%), the other 50% are hepatically metabolised, whereas metoprolol and carvedilol are metabolised by CYP2D6. [SEP]Relations: Metoprolol has relations: drug_protein with CYP2D6, drug_protein with CYP2D6, drug_protein with CYP3A4, drug_protein with CYP3A4, drug_protein with ADRB2, drug_protein with ADRB2, drug_drug with NN344, drug_drug with NN344, drug_drug with Cyproterone acetate, drug_drug with Cyproterone acetate. Definitions: carvedilol defined as following: A carbazole and propanol derivative that acts as a non-cardioselective beta blocker and vasodilator. It has blocking activity for ALPHA 1 ADRENERGIC RECEPTORS and, at higher doses, may function as a blocker of CALCIUM CHANNELS; it also has antioxidant properties. Carvedilol is used in the treatment of HYPERTENSION; ANGINA PECTORIS; and HEART FAILURE. It can also reduce the risk of death following MYOCARDIAL INFARCTION.. metoprolol defined as following: A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.. bisoprolol defined as following: A cardioselective beta-1 adrenergic blocker. It is effective in the management of HYPERTENSION and ANGINA PECTORIS.. CYP2D6 defined as following: Cytochrome P450 2D6 (497 aa, ~56 kDa) is encoded by the human CYP2D6 gene. This protein plays a role in flavoprotein metabolism..", "label": "yes"} {"id": "converted_3978", "sentence1": "Can radiosurgery be used for the DNET tumors?", "sentence2": "Salvage gamma knife radiosurgery in the management of dysembryoplastic neuroepithelial tumors: Long-term outcome in a single-institution case series., BACKGROUND: Dysembryoplastic neuroepithelial tumors (DNT/DNET) are rare epileptogenic tumors. Microsurgery remains the best treatment option, although case reports exist on the use of gamma knife radiosurgery (GKRS) in selected cases. We investigated the long-term outcome of GKRS-treated DNTs at our institution in the context of current diagnostic and treatment options., Long-term seizure control was obtained after GKRS of two separate residual DNT components along the surgical margin (2005 and 2010). A 27-year-old male undergoing gross total resection of the contrast-enhancing portion of a DNT (1999) resulted in temporary control of intractable epilepsy despite AEDs; lasting clinical control of seizures was achieved in 2002 after GKRS of a small, recurrent DNT component. A 28-year-old male underwent STR of DNT (1994 and 2004) resulting in temporary control of intractable epilepsy. Lasting seizure control was gained after GKRS of a residual tumor (2005).CONCLUSION: GKRS as performed in our series was effective in terms of tumor and seizure control., Prospective studies are warranted to establish the role of GKRS in the treatment of DNTs., Two rare cases of intractable epilepsy caused by Dysembryoplastic Neuroepithelial Tumours (DNET) are reported and their different management discussed. The first case required vagal nerve stimulation and radiosurgery while the later was operated with the help of neuronavigation. , Salvage gamma knife radiosurgery in the management of dysembryoplastic neuroepithelial tumors: Long-term outcome in a single-institution case series[SEP]Relations: epilepsy has relations: contraindication with Foscarnet, contraindication with Foscarnet, contraindication with Dyclonine, contraindication with Dyclonine, contraindication with Desonide, contraindication with Desonide, contraindication with Triprolidine, contraindication with Triprolidine. Dysembryoplastic neuroepithelial tumor has relations: phenotype_phenotype with Neuronal/glioneuronal neoplasm of the central nervous system, phenotype_phenotype with Neuronal/glioneuronal neoplasm of the central nervous system. Definitions: Dysembryoplastic neuroepithelial tumors defined as following: A benign glial-neuronal neoplasm. It is usually supratentorial, located in the cortex. It occurs in children and young adults with a long-standing history of partial seizures. A histologic hallmark of this tumor is the 'specific glioneuronal element', characterized by columns, made up of bundles of axons, oriented perpendicularly to the cortical surface. (Adapted from WHO). seizures defined as following: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\". AEDs defined as following: An arrhythmia detector and alarm is a system that monitors the electrocardiogram and is designed to produce a visible or audible signal or alarm when an atrial or ventricular arrhythmia, such as a premature contraction or ventricular fibrillation, exists.. epilepsy defined as following: A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313).", "label": "yes"} {"id": "converted_1953", "sentence1": "Is ABCE1 involved in ribosomal recycling?", "sentence2": "Ribosome recycling orchestrated by the ATP binding cassette (ABC) protein ABCE1 can be considered as the final-or the first-step within the cyclic process of protein synthesis, connecting translation termination and mRNA surveillance with re-initiation., Recent studies have identified ABCE1 as a ribosome-recycling factor important for translation termination in mammalian cells, yeast and also archaea., d a termination/prerecycling complex containing eRF1-ABCE1, ABCE1, a eukaryotic ribosome recycling factor[SEP]Relations: ABCE1 has relations: protein_protein with RNASEL, protein_protein with RNASEL, protein_protein with RNF2, protein_protein with RNF2, protein_protein with CDC6, protein_protein with CDC6, bioprocess_protein with ribosomal subunit export from nucleus, bioprocess_protein with ribosomal subunit export from nucleus, protein_protein with DNM1L, protein_protein with DNM1L. Definitions: yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. ribosomal defined as following: Multicomponent ribonucleoprotein structures found in the CYTOPLASM of all cells, and in MITOCHONDRIA, and PLASTIDS. They function in PROTEIN BIOSYNTHESIS via GENETIC TRANSLATION..", "label": "yes"} {"id": "converted_1333", "sentence1": "Can cognitive behavioral therapy improve fatigue in cancer patients?", "sentence2": "Physical activity, educational interventions, and cognitive-behavioral therapy have the most supportive data and can be recommended to patients with confidence. , For women undergoing radiotherapy (3 RCTs), hypnosis combined with cognitive-behavioral therapy improved distress and fatigue., Patients in the CBT group reported a significantly larger decrease in fatigue scores than patients in the waiting list group., However, relative to VCBT-I, PCBT-I was associated with significantly greater improvements of insomnia severity, early morning awakenings, depression, fatigue, and dysfunctional beliefs about sleep. , CBT-I may also improve mood, fatigue, and overall quality of life, and can be successfully delivered through a variety of treatment modalities, making it possible to reach a broader range of patients who may not have access to more traditional programs. , No group differences in improvement were noted relative to QOL, fatigue, or mood. , In case of persistent fatigue, personalized cognitive behavioral therapy can be considered., ONCLUSION: The results support CBTH as an evidence-based intervention to control fatigue in patients undergoing radiotherapy for breast cancer. , Severe fatigue after cancer treatment can be treated effectively with cognitive behavioral therapy (CBT), but it is unclear whether CBT has an effect on cognitive functioning., CONCLUSION: CBT for post-cancer fatigue has already been shown to be an effective therapy. , Frequently reported side effects include cancer-related fatigue, peripheral neuropathy, and psychological distress. Exercise and cognitive behavioral therapy interventions have counteracted such adverse effects in other cancer populations. , There is evidence from methodologically rigorous controlled trials that exercise, psycho-educational interventions, and cognitive-behavioral therapy for insomnia are effective in the treatment of CRF, and a wide range of pharmacologic and nonpharmacologic interventions has shown initial promise in single-arm pilot studies with small, heterogeneous samples. , CONCLUSIONS: Physical training combined with cognitive-behavioral therapy and physical training alone had significant and beneficial effects on fatigue compared with no intervention. Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training., RESULTS: Imagery/hypnosis and CBT/CST interventions have produced improvement in all the three cancer-related symptoms individually: pain, fatigue, and sleep disturbance., RESULTS: Multilevel modeling indicated that for weekly FACIT fatigue data, there was a significant effect of the CBTH intervention on the rate of change in fatigue (p < .05), such that on average, CBTH participants' fatigue did not increase over the course of treatment, whereas control group participants' fatigue increased linearly., ONCLUSION: The results suggest that CBTH is an effective means for controlling and potentially preventing fatigue in breast cancer radiotherapy patients., Results were consistent with the view that CBTH was effective in managing fatigue and skin discomfort, and increasing relaxation., RESULTS: Participants in the Internet group showed significant improvements at post-assessment compared with those in the control group in overall insomnia severity (F(1,26) = 22.8; p<0.001), sleep efficiency (F(1,24) = 11.45; P = 0.002), sleep onset latency (F(1,24) = 5.18; P = 0.03), soundness of sleep (F(1,24) = 9.34; P = 0.005), restored feeling upon awakening (F(1,24) = 11.95; P = 0.002), and general fatigue (F(1,26) = 13.88; P = 0.001). , Cognitive-behavior therapy (CBT) has alleviated fatigue and improved QOL of cancer patients; however, little is known about the effects of nurse-led CBT on breast cancer patients undergoing radiotherapy., Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training., Cognitive-behavior therapy (CBT) has alleviated fatigue and improved QOL of cancer patients; however, little is known about the effects of nurse-led CBT on breast cancer patients undergoing radiotherapy., Physical training was equally effective as or more effective than physical training combined with cognitive-behavioral therapy in reducing cancer-related fatigue, suggesting that cognitive-behavioral therapy did not have additional beneficial effects beyond the benefits of physical training., The positive effects of cognitive behavioral therapy in adolescents with chronic fatigue syndrome are sustained after cognitive behavioral therapy[SEP]Relations: Fatigue has relations: phenotype_phenotype with Cognitive fatigue, phenotype_phenotype with Cognitive fatigue, drug_effect with Nevirapine, drug_effect with Nevirapine, drug_effect with Parathyroid hormone, drug_effect with Parathyroid hormone, drug_effect with Mitomycin, drug_effect with Mitomycin, drug_effect with Betahistine, drug_effect with Betahistine. Definitions: peripheral neuropathy defined as following: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.. breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. CBT-I defined as following: A structured program that helps the patient identify and replace thoughts and behaviors that cause or worsen sleep problems with habits that promote sound sleep. Techniques include stimulus control therapy, sleep restriction, sleep hygiene, sleep environment improvement, relaxation training, remaining passively awake, and biofeedback.. sleep disturbance defined as following: Conditions characterized by disturbances of usual sleep patterns or behaviors. SLEEP WAKE DISORDERS may be divided into three major categories: DYSSOMNIAS (i.e. disorders characterized by insomnia or hypersomnia), PARASOMNIAS (abnormal sleep behaviors), and SLEEP WAKE DISORDERS secondary to medical or psychiatric disorders. (From Thorpy, Sleep Disorders Medicine, 1994, p187). CRF defined as following: A peptide of about 41 amino acids that stimulates the release of ADRENOCORTICOTROPIC HORMONE. CRH is synthesized by neurons in the PARAVENTRICULAR NUCLEUS of the HYPOTHALAMUS. After being released into the pituitary portal circulation, CRH stimulates the release of ACTH from the PITUITARY GLAND. CRH can also be synthesized in other tissues, such as PLACENTA; ADRENAL MEDULLA; and TESTIS.. fatigue defined as following: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.. chronic fatigue syndrome defined as following: A syndrome characterized by persistent or recurrent fatigue, diffuse musculoskeletal pain, sleep disturbances, and subjective cognitive impairment of 6 months duration or longer. Symptoms are not caused by ongoing exertion; are not relieved by rest; and result in a substantial reduction of previous levels of occupational, educational, social, or personal activities. Minor alterations of immune, neuroendocrine, and autonomic function may be associated with this syndrome. There is also considerable overlap between this condition and FIBROMYALGIA. (From Semin Neurol 1998;18(2):237-42; Ann Intern Med 1994 Dec 15;121(12): 953-9). cancer defined as following: A malignant tumor at the original site of growth..", "label": "yes"} {"id": "converted_728", "sentence1": "Is the Prostate- Specific Antigen (PSA) test relevant only for prostate cancer?", "sentence2": "rostate cancer (PCa) is the most frequently diagnosed malignancy and the second leading cause of cancer death in men, PSA is known to be prostate specific, but not PCa specific, deficiencies of serum PSA as a prostate-cancer-specific diagnostic test are well recognized., medical debate surrounding the use of the prostate-specific antigen (PSA) test for prostate cancer screening, The clinical relevance of this surprisingly high rate of prostate cancer in men with a normal PSA is yet to be determined , Rapid uptake of prostate-specific antigen (PSA) testing has occurred in the United States despite inconclusive evidence regarding mortality benefit, Routine cancer screening with prostate-specific antigen (PSA) is controversial, and practice guidelines recommend that men be counseled about its risks and benefits, Prostate carcinoma was histologically confirmed in 14 (0.66%) of the men, nine times in the early stage (T2) and five times in the clinical stage (T3), corresponding to an incidence of circa 650 cases per 100,000 men in the target age group, This newly developed PSA test system can enhance the acceptance rate and effectiveness of medical check-ups for prostate cancer,, PSA can be used reliably as a unique tool in the follow-up of patients for the early detection of progressive disease, PSA showed negative predictive values of 82 and 77%, respectively, using 4 and 10 ng/ml as cutoff points, have assessed the feasibility of using fixed-limit criteria based on medical relevance and biological variation for evaluating the analytical performance of the prostate-specific antigen (PSA) test[SEP]Relations: prostate carcinoma has relations: disease_protein with PSCA, disease_protein with PSCA, disease_protein with PSMC3IP, disease_protein with PSMC3IP, disease_protein with HSPA1A, disease_protein with HSPA1A, disease_disease with prostate cancer, disease_disease with prostate cancer, disease_protein with PCAT1, disease_protein with PCAT1. Definitions: malignancy defined as following: A malignant tumor at the original site of growth.. prostate cancer defined as following: A primary or metastatic malignant tumor involving the prostate gland. The vast majority are carcinomas.. prostate-specific antigen defined as following: Prostate-specific antigen (261 aa, ~29 kDa) is encoded by the human KLK3 gene. This protein plays a role in both proteolysis and seminal fluid liquefaction.. PSA defined as following: A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.. PCa defined as following: Relief of PAIN, without loss of CONSCIOUSNESS, through ANALGESIC AGENTS administered by the patients. It has been used successfully to control POSTOPERATIVE PAIN, during OBSTETRIC LABOR, after BURNS, and in TERMINAL CARE. The choice of agent, dose, and lockout interval greatly influence effectiveness. The potential for overdose can be minimized by combining small bolus doses with a mandatory interval between successive doses (lockout interval).. Prostate carcinoma defined as following: One of the most common malignant tumors afflicting men. The majority of carcinomas arise in the peripheral zone and a minority occur in the central or the transitional zone of the prostate gland. Grossly, prostatic carcinomas appear as ill-defined yellow areas of discoloration in the prostate gland lobes. Adenocarcinomas represent the overwhelming majority of prostatic carcinomas. Prostatic-specific antigen (PSA) serum test is widely used as a screening test for the early detection of prostatic carcinoma. Treatment options include radical prostatectomy, radiation therapy, androgen ablation and cryotherapy. Watchful waiting or surveillance alone is an option for older patients with low-grade or low-stage disease.. cancer death defined as following: A death attributed to the progression of a cancer-related pathologic condition..", "label": "no"} {"id": "converted_3523", "sentence1": "Is SATB1 positioned close to AT-rich sequences?", "sentence2": " Tryptic cleavage and peptide sequence analysis demonstrated that the 98-kD protein is identical to a recently cloned protein, special A-T-rich binding protein 1 (SATB1), Special AT-rich sequence-binding protein 1 (SATB1), a DNA-binding protein expressed predominantly in thymocytes, recognizes an ATC sequence context that consists of a cluster of sequence stretches with well-mixed A's, T's, and C's without G's on one strand. , We have purified and identified one of the core factors as the matrix attachment region (MAR) binding protein, SATB1, which is known to bind to AT-rich sequences with a high propensity to unwind, SATB1 (special AT-rich sequence-binding protein-1) provides a key link between DNA loop organization, chromatin modification/remodeling, and association of transcription factors at matrix attachment regions (MARs)., Over-expression of the special AT rich sequence binding protein 1 (SATB1) promotes the progression of nasopharyngeal carcinoma: association with EBV LMP-1 expression., pecial AT rich sequence binding protein 1 (SATB1) plays a crucial role in the biology of various types of human cancer. , Loss of special AT-rich sequence-binding protein 1 (SATB1), Special AT-rich sequence-binding protein 1 (SATB1) is a cell type-specific matrix attachment region binding protein, functioning as a global genome organizer. , SATB1 (special AT-rich binding protein 1) is a global chromatin organizer regulating the expression of a large number of genes, Special AT-rich Sequence-binding Protein 1 (SATB1) Functions as an Accessory Factor in Base Excision Repair., Rearrangement of the Chromatin Organizer Special AT-rich Binding Protein 1 Gene, The Special AT-rich Sequence Binding Protein 1 (SATB1) exerts multiple functions, by influencing the structural organization of chromatin and interacting with several co-activators and co-repressors of transcription., The Special AT-rich Sequence Binding Protein 1 (SATB1) and its role in solid tumors.[SEP]Relations: protein binding has relations: molfunc_protein with SATB1, molfunc_protein with SATB1, molfunc_protein with URB1-AS1, molfunc_protein with URB1-AS1, molfunc_protein with SETBP1, molfunc_protein with SETBP1, molfunc_protein with SATB2, molfunc_protein with SATB2, molfunc_protein with SAT1, molfunc_protein with SAT1. Definitions: matrix attachment region defined as following: Regions of the CHROMATIN or DNA that bind to the NUCLEAR MATRIX. They are found in INTERGENIC DNA, especially flanking the 5' ends of genes or clusters of genes. Many of the regions that have been isolated contain a bipartite sequence motif called the MAR/SAR recognition signature sequence that binds to MATRIX ATTACHMENT REGION BINDING PROTEINS.. nasopharyngeal carcinoma defined as following: A carcinoma that originates in the EPITHELIUM of the NASOPHARYNX and includes four subtypes: keratinizing squamous cell, non-keratinizing, basaloid squamous cell, and PAPILLARY ADENOCARCINOMA. It is most prevalent in Southeast Asian populations and is associated with EPSTEIN-BARR VIRUS INFECTIONS. Somatic mutations associated with this cancer have been identified in NPCR, BAP1, UBAP1, ERBB2, ERBB3, MLL2, PIK3CA, KRAS, NRAS, and ARID1A genes.. co-repressors defined as following: A subclass of repressor proteins that do not directly bind DNA. Instead, co-repressors generally act via their interaction with DNA-BINDING PROTEINS such as a TRANSCRIPTIONAL SILENCING FACTORS or NUCLEAR RECEPTORS.. solid tumors defined as following: A benign or malignant neoplasm arising from tissues that do not include fluid areas. Representative examples include epithelial neoplasms (e.g. lung carcinoma, prostate carcinoma, breast carcinoma, colon carcinoma), and neoplasms arising from the soft tissues and bones (e.g. leiomyosarcoma, liposarcoma, chondrosarcoma, osteosarcoma). Neoplasms originating from the blood or bone marrow (leukemias and myeloproliferative disorders) are not considered solid tumors.. SATB1 defined as following: DNA-Binding Protein SATB1 (763 aa, ~86 kDa) is encoded by the human SATB1 gene. This protein binds DNA and may be involved in the regulation of transcription.. cluster defined as following: A grouping of a number of similar things.. thymocytes defined as following: HEMATOPOIETIC PROGENITOR CELLS that have migrated to the THYMUS where they differentiate into T-LYMPHOCYTES. Thymocytes are classified into maturational stages based on the expression of CELL SURFACE ANTIGENS.. AT defined as following: An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. LMP-1 defined as following: Latent membrane protein 1 (386 aa, ~42 kDa) is encoded by the Epstein-Barr virus LMP1 gene. This protein is involved in both the activation of nuclear factor-kappa-B family signaling pathways and the inhibition of apoptosis of infected B-lymphocytes.. DNA-binding protein defined as following: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.. transcription factors defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process..", "label": "yes"} {"id": "converted_1169", "sentence1": "Have microRNAs been implicated in pharmacogenomics? ", "sentence2": "A major discovery is the ability of miRNAs to determine the efficacy of drugs, which has given rise to the field of 'miRNA pharmacogenomics' through 'Pharmaco-miRs'. miRNAs play a significant role in pharmacogenomics by down-regulating genes that are important for drug function., The potential modulation of toxicology-related changes in miRNA expression, the role of miRNA in immune-mediated drug-induced liver injuries, the use of circulating miRNAs in body fluids as potential toxicological biomarkers, and the link between miRNA-related pharmacogenomics and adverse drug reactions are highlighted., Single nucleotide polymorphisms (SNPs) in the miRNA target sequences may affect or impair the binding of miRNAs. Studies have shown that SNPs in miRNA target sites (miR-TS-SNPs) have a great influence on diverse biological functions, including pharmacogenomics and disease susceptibilities in human., Pharmacogenomics genes can be divided into drug target genes termed as pharmacodynamics genes (PD) and genes involved in drug transport and metabolism termed as pharmacokinetics genes (PK). To clarify the regulatory potential of miRNAs in pharmacogenomics, we have examined the potential regulation by miRNAs of PK and PD genes., Our analysis identify a striking difference in the level of miRNA regulation between PK and PD genes, with the former having less than half predicted conserved miRNA binding sites compared with the latter. Importantly, this finding is reflected in a highly significant difference in the shift in expression levels of PD versus PK genes after depletion of miRNAs. CONCLUSIONS: Our study emphasizes an intrinsic difference between PK and PD genes and helps clarify the role of miRNAs in pharmacogenomics., Pharmacogenomics, toxicogenomics, and small RNA expression analysis are three of the most active research topics in the biological, biomedical, pharmaceutical, and toxicological fields. All of these studies are based on gene expression analysis, which requires reference genes to reduce the variations derived from different amounts of starting materials and different efficiencies of RNA extraction and cDNA synthesis., In contrast, hTBCA and small RNAs are more stable during drug treatment, and they are better reference genes for pharmacogenomics and toxicogenomics studies., Polymorphisms of genes involved in the pharmacokinetic and pharmacodynamic processes underlie the divergent drug responses among individuals., A panel of drug-response genes was constructed, which contains 923 pharmacokinetic genes, 703 pharmacodynamic genes and 720 miRNAs., miRNA variations can affect drug resistance, efficacy, and metabolism, opening new avenues of pharmacogenomics research., we studied the pharmacologic roles of three microRNAs previously implicated in cancer biology (let-7i, mir-16, and mir-21) and also used in silico methods to test pharmacologic microRNA effects more broadly., n silico comparison of drug potencies with microRNA expression profiles across the entire NCI-60 panel revealed that approximately 30 microRNAs, including mir-21, show highly significant correlations with numerous anticancer agents. Ten of those microRNAs have already been implicated in cancer biology. Our results support a substantial role for microRNAs in anticancer drug response, suggesting novel potential approaches to the improvement of chemotherapy., The NCI-60 has also been profiled for mRNA and protein expression, mutational status, chromosomal aberrations, and DNA copy number, generating an unparalleled public resource for integrated chemogenomic studies., To complement the existing NCI-60 data sets, we have measured expression levels of microRNAs in the NCI-60 and incorporated the resulting data into the CellMiner program package for integrative analysis., . Comparison of microRNA expression patterns and compound potency patterns showed significant correlations, suggesting that microRNAs may play a role in chemoresistance. Combined with gene expression and other biological data using multivariate analysis, microRNA expression profiles may provide a critical link for understanding mechanisms involved in chemosensitivity and chemoresistance., This study reports on miRNAs implicated in SSRI sensitivity of LCLs., these miRNAs as tentative SSRI response biomarkers awaits validation with lymphocyte samples of major depression patients.[SEP]Relations: Viral Messenger RNA Synthesis has relations: pathway_protein with NDC1, pathway_protein with NDC1, pathway_protein with AAAS, pathway_protein with AAAS, pathway_protein with RAE1, pathway_protein with RAE1, pathway_protein with NUP107, pathway_protein with NUP107, pathway_protein with NUP188, pathway_protein with NUP188. Definitions: microRNA defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. NCI-60 defined as following: A panel of 60 different human cancer cell lines grown in culture that were selected to be used in a drug-screening program to identify and characterize novel compounds for growth inhibition or killing of tumor cell lines.. mir-16 defined as following: A 22 ribonucleotide sequence that is a final product of the processing of either MIR16-1 pre-miRNA or MIR16-2 pre-miRNA. This oligonucleotide may be involved in the negative regulation of gene expression.. PD defined as following: A score of 4 or 5 on a 5-point PET scale with an increase in intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment.. RNAs defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). Single nucleotide polymorphisms defined as following: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.. human defined as following: Members of the species Homo sapiens.. mir-21 defined as following: This gene is involved in the regulation of gene expression and plays an oncogenic role in hepatocellular, breast, esophageal, gastric, pancreatic, prostatic and squamous cell carcinomas, glioblastoma and glioma.. adverse drug reactions defined as following: Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.. PK defined as following: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. microRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing..", "label": "yes"} {"id": "converted_3962", "sentence1": "Is MIS-C or Multisystem Inflammatory syndrome in children a complication of Covid-19?", "sentence2": "Much remains unknown about the risk factors, pathogenesis, prognosis, and specific therapy for this emerging manifestation of COVID-19 known as Multisystem Inflammatory Syndrome in Children (MIS-C)., Multisystem Inflammatory Syndrome in Children During the Coronavirus 2019 Pandemic: A Case Series, COVID-19 and Multisystem Inflammatory Syndrome in Latin American Children, This study aims to assess COVID-19 and Multisystem Inflammatory Syndrome (MIS-C) in Latin American children,, A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation., We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage., OBJECTIVE: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease (COVID-19) is a rare and challenging diagnosis requiring early treatment., This syndrome is now known as either \"Pediatric Inflammatory Multisystem Syndrome temporally related with COVID-19\" (PIMS-TS) (1), or Multisystem Inflammatory Syndrome in Children (MIS-C) (2) and is currently considered a rare post-COVID-19 complication which, in a minority of cases, can lead to death., Multisystem Inflammatory Syndrome in Children (MIS-C) associated with Coronavirus Disease 2019 (COVID-19) is a newly recognized condition in which children with recent SARS-CoV-2 infection present with a constellation of symptoms including hypotension, multiorgan involvement, and elevated inflammatory markers. Thes, Background: Kawasaki-like syndrome occurring in children during the COVID-19 pandemic has been labelled multisystem inflammatory syndrome in children (MIS-C) by the CDC and paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS) by , em inflammatory syndrome in children (MIS-C), a possible complication of COVID-19, has been described as a hyperinflammatory condition with multiorgan involvement similar to that in Kawasaki disease or toxic shock syndrome in children with evidence of SARS-CoV-2 infection. This revie, BACKGROUND: A small subset of pediatric patients develop a rare syndrome associated with Coronavirus Disease 2019 (COVID-19) infection called multisystem inflammatory syndrome in childr, adults. However, the newly described multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been associated with cardiac complicat, BACKGROUND: Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection i, OBJECTIVE: Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease (COVID-19) is a rare and challenging diagnosis requiring early tr, Background: Multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory multisystem syndrome, is a new dangerous childhood disease that is temporally associated with coronavirus disease 2019 (, Recent COVID-19 publications describe a variety of clinical presentations including an asymptomatic state, pneumonia, a hemophagocytic lymphohistiocytosis like syndrome, Multisystem Inflammatory Syndrome in Children (MIS-C) but, also called Pediatric Inflammatory Multisystem Syndrome-Toxic Shock (PIMS-TS), Kawasaki Disease, and myocarditis., We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission., Multisystem inflammatory syndrome in children (MIS-C), a possible complication of COVID-19, has been described as a hyperinflammatory condition with multiorgan involvement similar to that in Kawasaki disease or toxic shock syndrome in children with evidence of SARS-CoV-2 infection., It includes a discussion of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, as well as other aspects of the COVID-19 pandemic that are affecting children and families, such as poisonings, childhood immunizations, mental health, nonaccidental trauma, and neglect., Importance: To date, no study has characterized the mucocutaneous features seen in hospitalized children with multisystem inflammatory syndrome in children (MIS-C) or the temporal association of these findings with the onset of systemic symptoms.Objective: To describe the mucocutaneous findings seen in children with MIS-C during the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City in 2020.Design, Setting, and Participants: A retrospective case series was conducted of 35 children admitted to 2 hospitals in New York City between April 1 and July 14, 2020, who met Centers for Disease Control and Prevention and/or epidemiologic criteria for MIS-C.Main Outcomes and Measures: Laboratory and clinical characteristics, with emphasis on mucocutaneous findings, of children who met criteria for MIS-C., This condition, since defined as the multisystem inflammatory syndrome in children (MIS-C), is assumed to be a delayed immune response to coronavirus disease 2019 (COVID-19), and there are frequently cardiac manifestations of ventricular dysfunction and/or coronary artery dilation.Methods: We surveyed the inpatient MIS-C management approaches of the members of the International Kawasaki Disease Registry across 38 institutions and 11 countries.Results: Among the respondents, 56% reported using immunomodulatory treatment for all MIS-C patients, regardless of presentation., DESIGN: Children ages 0-22 years with suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presenting to urgent care clinics or being hospitalized for confirmed/suspected SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) at Massachusetts General Hospital were offered enrollment in the Massachusetts General Hospital Pediatric COVID-19 Biorepository., We recently discovered a superantigen-like motif, similar to Staphylococcal enterotoxin B (SEB), near the S1/S2 cleavage site of SARS-CoV-2 Spike protein, which might explain the multisystem-inflammatory syndrome (MIS-C) observed in children and cytokine storm in severe COVID-19 patients., METHODS: An extensive search strategy was conducted by combining the terms multisystem inflammatory syndrome in children and coronavirus infection or using the term multisystem inflammatory syndrome in children in bibliographic electronic databases (PubMed, EMBASE, and CINAHL) and in preprint servers (BioRxiv.org and MedRxiv.org) following the Preferred Reporting Items for Systematic Reviews and Metaanalyses guidelines to retrieve all articles published from January 1, 2020, to July 31, 2020., Here, we show that pediatric patients with multisystem inflammatory syndrome in children (MIS-C) possess higher SARS-CoV-2 spike IgG titers compared to those with severe coronavirus disease 2019 (COVID-19), likely reflecting a longer time since onset of infection in MIS-C patients., Here, we show that pediatric patients with multisystem inflammatory syndrome in children (MIS-C) possess higher SARS-CoV-2 spike IgG titers compared to those with severe coronavirus disease 2019 (COVID-19), likely reflecting a longer time since onset of infection in MIS-C patients., Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children., Data on multisystem inflammatory syndrome in children (MIS-C) related to coronavirus disease-19 (COVID-19) is increasing in the current COVID-19 pandemic., Introduction Multisystem inflammatory syndrome in children (MIS-C) is a unique clinical complication of SARS-CoV-2 infection observed in pediatric patients., New onset diabetes with diabetic ketoacidosis in a child with multisystem inflammatory syndrome due to COVID-19., Case presentation An eight-year-old female presented with hyperglycemia, ketosis and metabolic acidosis consistent with diabetic ketoacidosis (DKA) in the setting of fever, rash, respiratory distress, hemodynamic instability, reduced systolic function with dilation of the left anterior descending artery, and positive SARS-CoV-2 antibodies suggestive of MIS-C., However, the newly described multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been associated with cardiac complications.M, Toxic shock-like syndrome and COVID-19: Multisystem inflammatory syndrome in children (MIS-C)., Many of these cases feature a toxic shock-like syndrome or Kawasaki-like syndrome in the setting of SARS-CoV-2 positive diagnostic testing and the CDC has termed this presentation Multisystem Inflammatory Syndrome (MIS-C)., We describe a case of MIS-C in a child who presented to our Emergency Department (ED) twice and on the second visit was found to have signs of distributive shock, multi-organ injury and systemic inflammation associated with COVID-19., PURPOSE OF REVIEW: Here we summarize current knowledge about multisystem inflammatory syndrome in children (MIS-C), a presumed postinfectious inflammatory condition that has emerged as an important COVID-19-associated complication, to help clinicians identify and manage cases.RECENT FINDINGS: Clinical presentation of MIS-C is do, MIS-C is a rare yet severe and highly critical complication of COVID-19 infection in pediatrics, leading to serious and life-threatening illnesses., BACKGROUND: A multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) has recently been described.OBJECTIVE: To evaluate imaging findings of MIS-C associated with COVID-19.SUBJECTS AND METHODS: Imaging studies and medical records of sixteen patients (0-20 years) admit, BACKGROUND: Recently, cases of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 have been reporte, Recent reports have described a secondary Multisystem Inflammatory Syndrome in Children (MIS-C) after a prior COVID-19 infection that often has features of Kawasaki disease (KD)., discharged home (length of hospital stay 3-20 days). There were no mortalities.CONCLUSION: MIS-C associated with COVID-19 is characterized predominantly by cardiovascular abnormalities, though also solid visceral organ, gallbladder, and bowel abnormalities as well as ascites, reflecting a multisystemic inflammatory process.CLINICAL IMPACT: The constellation of imaging findings in the setting of COVID-19 may alert pediatr, Multisystem Inflammatory Syndrome in Children Temporally Related to COVID-19: A Case Report From Saudi Arabia., BACKGROUND: Multisystem inflammatory syndrome temporally associated with COVID-19 (MIS-C) has been described as a novel and often severe presentation of SARS-CoV-2 infection , ric patients. An association between COVID-19 and a Kawasaki-like inflammatory syndrome has recently presented in pediatric patients.CASE REPORT: We report a unique case of multisystem inflammatory syndrome in children presenting with characteristic findings in a child who later developed cardiogenic shock requiring venoarterial extracorporeal membrane oxygenation.CONCLUSION: Recognition of these early signs and symptoms facilitates screening and risk stratification of pediatric COVID-19 cas, Severe cardiac dysfunction in a patient with multisystem inflammatory syndrome in children associated with COVID-19: Retrospective diagnosis of a puzzling presentation. A case report.[SEP]Relations: Portal inflammation has relations: disease_phenotype_positive with FADD-related immunodeficiency, disease_phenotype_positive with FADD-related immunodeficiency. Respiratory distress has relations: disease_phenotype_positive with progressive supranuclear palsy-corticobasal syndrome, disease_phenotype_positive with progressive supranuclear palsy-corticobasal syndrome, disease_phenotype_positive with cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency, disease_phenotype_positive with cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency. colitis (disease) has relations: disease_protein with MIF, disease_protein with MIF. Ascites has relations: disease_phenotype_positive with fetal parvovirus syndrome, disease_phenotype_positive with fetal parvovirus syndrome. Definitions: T cell subsets defined as following: A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.. SEB defined as following: A bacterial enterotoxin with potential immunostimulatory activity. Staphylococcal enterotoxin B (SEB), a gram positive superantigen produced by Staphylococcus aureus, is a potent stimulator of T-cell activation. SEB binds directly to class II major histocompatibility complex (MHC) molecules and the V beta region of the T-cell receptor (TCR), leading to an amplified T-cell response. In response to SEB, both CD4+ and CD8+ cells proliferate, secrete cytokines and demonstrate enhanced cytotoxic activity against a broad range of antigens. Co-administration of SEB with interleukin-2 (IL-2) by direct injection into tumor cells, may induce clonal T-cell expansion and potentiate apoptosis of tumor cells, resulting in decreased tumor growth.. DKA defined as following: A life-threatening complication of diabetes mellitus, primarily of TYPE 1 DIABETES MELLITUS with severe INSULIN deficiency and extreme HYPERGLYCEMIA. It is characterized by KETOSIS; DEHYDRATION; and depressed consciousness leading to COMA.. cytokine defined as following: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. pneumonia defined as following: Infection of the lung often accompanied by inflammation.. ketosis defined as following: A condition characterized by an abnormally elevated concentration of KETONE BODIES in the blood (acetonemia) or urine (acetonuria). It is a sign of DIABETES COMPLICATION, starvation, alcoholism or a mitochondrial metabolic disturbance (e.g., MAPLE SYRUP URINE DISEASE).. coronavirus defined as following: Virus diseases caused by the CORONAVIRUS genus. Some specifics include transmissible enteritis of turkeys (ENTERITIS, TRANSMISSIBLE, OF TURKEYS); FELINE INFECTIOUS PERITONITIS; and transmissible gastroenteritis of swine (GASTROENTERITIS, TRANSMISSIBLE, OF SWINE).. autoantibodies defined as following: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.. rash defined as following: Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (ERYTHEMA INFECTIOSUM), and sixth (EXANTHEMA SUBITUM) numeric designations survive as occasional synonyms in current terminology.. poisonings defined as following: A condition or physical state produced by the ingestion, injection, inhalation of or exposure to a deleterious agent.. cardiogenic shock defined as following: Shock resulting from diminution of cardiac output in heart disease.. SARS-CoV-2 infection defined as following: A viral disorder generally characterized by high FEVER; COUGH; DYSPNEA; CHILLS; PERSISTENT TREMOR; MUSCLE PAIN; HEADACHE; SORE THROAT; a new loss of taste and/or smell (see AGEUSIA and ANOSMIA) and other symptoms of a VIRAL PNEUMONIA. In severe cases, a myriad of coagulopathy associated symptoms often correlating with COVID-19 severity is seen (e.g., BLOOD COAGULATION; THROMBOSIS; ACUTE RESPIRATORY DISTRESS SYNDROME; SEIZURES; HEART ATTACK; STROKE; multiple CEREBRAL INFARCTIONS; KIDNEY FAILURE; catastrophic ANTIPHOSPHOLIPID ANTIBODY SYNDROME and/or DISSEMINATED INTRAVASCULAR COAGULATION). In younger patients, rare inflammatory syndromes are sometimes associated with COVID-19 (e.g., atypical KAWASAKI SYNDROME; TOXIC SHOCK SYNDROME; pediatric multisystem inflammatory disease; and CYTOKINE STORM SYNDROME). A coronavirus, SARS-CoV-2, in the genus BETACORONAVIRUS is the causative agent.. cardiovascular abnormalities defined as following: Congenital, inherited, or acquired anomalies of the CARDIOVASCULAR SYSTEM, including the HEART and BLOOD VESSELS.. death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. hypotension defined as following: Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.. ascites defined as following: Accumulation or retention of free fluid within the peritoneal cavity.. toxic shock syndrome defined as following: Staphylococcal toxic shock syndrome (staphylococcal TSS) is an acute disease mediated by the production of superantigenic toxins, characterized by high fever, skin rash followed by skin peeling, hypotension, vomiting, diarrhea and potentially leading to multisystem organ failure and caused by a <i>Staphylococcus aureus</i> bacterial infection.. infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. respiratory distress defined as following: A pathological increase in the effort and frequency of breathing movements.. ventricular dysfunction defined as following: A condition in which HEART VENTRICLES exhibit impaired function.. toxic defined as following: The finding of bodily harm due to the poisonous effects of something.. myocarditis defined as following: Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies..", "label": "yes"} {"id": "converted_1405", "sentence1": "Can tetracycline affect tooth formation?", "sentence2": "he results of that study, reported earlier (Rebich et al., 1983), indicated that over one-fifth of the American Indian children had discoloration of the dentition due to ingestion of tetracycline during the years of tooth formatio, ale Wistar rats prelabeled with tetracycline to mark surfaces of bone and tooth formation-mineralization were placed into orbit for 18.5 days aboard the Soviet COSMOS-1129 Biosatellit, It was concluded that the increased tetracycline incorporation reflected a higher rate of mineralization associated with faster tooth formation in the unimpeded toot, n this investigation an attempt has been made to determine the relationship between the staining of permanent teeth by tetracycline administered during the period of tooth formation with the dosage of the drug and the duration of therap, definite relationship between total dosage and staining and duration of administration and staining was established; the condition occurred with greater frequency (in more than one-third of the children) when the total dosage exceeded 3 g. or the duration of treatment was longer than 10 days, This case report suggests the possibility that discoloration from tetracycline may not be limited to tooth development in the child, but may also affect the adult dentition[SEP]Relations: Tetracycline has relations: drug_effect with Hypoplasia of teeth, drug_effect with Hypoplasia of teeth, drug_effect with Nausea, drug_effect with Nausea, drug_effect with Glossitis, drug_effect with Glossitis, drug_effect with Vomiting, drug_effect with Vomiting, drug_effect with Arthralgia, drug_effect with Arthralgia. Definitions: drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. tetracycline defined as following: Any of a group of broad spectrum naphthacene antibiotics isolated from various species of Streptomyces or produced semisynthetically. In bacteria, tetracycline antibiotics block binding of aminoacyl-tRNA to the mRNA-ribosome complex, thereby inhibiting protein synthesis. (NCI05).", "label": "yes"} {"id": "converted_3754", "sentence1": "Glucoraphanin from broccoli can help reduce obesity , yes or no?", "sentence2": "Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance., A recent study demonstrated that glucoraphanin, a precursor of the Nrf2 activator sulforaphane, ameliorates obesity by enhancing energy expenditure and browning of white adipose tissue, and attenuates obesity-related inflammation and insulin resistance by polarizing M2 macrophages and reducing metabolic endotoxemia., Thus, this review focuses on the efficiency and safety of glucoraphanin in alleviating obesity, insulin resistance, and NAFLD., Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance, tudy demonstrated that glucoraphanin, a precursor of the Nrf2 activator sulforaphane, ameliorates obesity by enhancing energy expenditure and browning of white adipose tissue, and attenuates obesity-related inflammation and insulin resistance by polarizing M2 macrophages and reducing metabolic endotoxemia. Thus, this , iew focuses on the efficiency and safety of glucoraphanin in alleviating obesity, insulin resistance, and NAFLD. Abbreviations: [SEP]Relations: NFE2L2 has relations: anatomy_protein_present with Brodmann (1909) area 9, anatomy_protein_present with Brodmann (1909) area 9, anatomy_protein_present with Brodmann (1909) area 46, anatomy_protein_present with Brodmann (1909) area 46, bioprocess_protein with cellular response to glucose starvation, bioprocess_protein with cellular response to glucose starvation, protein_protein with GSK3B, protein_protein with GSK3B, protein_protein with GCLM, protein_protein with GCLM. Definitions: Nrf2 defined as following: This gene plays a role in transcriptional regulation.. NAFLD defined as following: A term referring to fatty replacement of the hepatic parenchyma which is not related to alcohol use..", "label": "yes"} {"id": "converted_2049", "sentence1": "Are the genes for marneral biosynthesis scattered in the genome of A. thaliana?", "sentence2": "Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation, Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation., Previously in thale cress (Arabidopsis thaliana) we identified an operon-like gene cluster that is required for the synthesis and modification of the triterpene thalianol., Prediction of operon-like gene clusters in the Arabidopsis thaliana genome based on co-expression analysis of neighboring genes, Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A. thaliana, compare the features of these two clusters, and investigate the evolutionary events that have led to cluster formation. , Here we characterize a second operon-like triterpene cluster (the marneral cluster) from A., the cyclic hydroxamic acid pathways in maize, the avenacin biosynthesis gene clusters in oat, the thalianol pathway in Arabidopsis thaliana, and the diterpenoid momilactone cluster in rice., Prediction of operon-like gene clusters in the Arabidopsis thaliana genome based on co-expression analysis of neighboring genes.[SEP]Relations: response to nickel cation has relations: bioprocess_protein with CACNA1G, bioprocess_protein with CACNA1G, bioprocess_bioprocess with cellular response to nickel ion, bioprocess_bioprocess with cellular response to nickel ion, bioprocess_bioprocess with response to metal ion, bioprocess_bioprocess with response to metal ion. Definitions: modification defined as following:Respond with exceptions, completions and modifications or revisions done before completion
. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. genome defined as following: Anatomical set of genes in all the chromosomes..", "label": "no"} {"id": "converted_672", "sentence1": "Is TREM2 associated with Alzheimer's disease?", "sentence2": "Absence of TREM2 polymorphisms in patients with Alzheimer's disease and Frontotemporal Lobar Degeneration, These data demonstrate that TREM2 coding region is highly conserved, implying a crucial role of this receptor. Further studies, including a functional analysis, are certainly required to clarify the role of TREM2 in neurodegenerative processes, Moreover, a rare TREM2 exon 2 variant (p.R47H) was reported to increase the risk of Alzheimer's disease (AD) with an odds ratio as strong as that for APOEε4, We observed an enrichment of rare variants across TREM2 in both AD and FTD patients compared to controls, most notably in the extracellular IgV-set domain, None of the rare variants individually reached significant association, but the frequency of p.R47H was increased ~ 3-fold in both AD and FTD patients compared to controls, in line with previous reports, Our data corroborate and extend previous findings to include an increased frequency of rare heterozygous TREM2 variations in AD and FTD, and show that TREM2 variants may play a role in neurodegenerative diseases in general., non-synonymous genetic rare variant, rs75932628-T (p.R47H), in the TREM2 gene has recently been reported to be a strong genetic risk factor for Alzheimer's disease (AD), These data strongly support the important role of p.R47H in AD risk, and suggest that this rare genetic variant is not related to FTD., Higher levels of TREM2 mRNA (p = 0.002) and protein (p < 0.001) were identified in AD patients, Our results indicate that TREM2 might serve as a novel noninvasive biomarker for AD diagnosis, studies have identified the rs75932628 (R47H) variant in TREM2 as an Alzheimer's disease risk factor with estimated odds ratio ranging from 2.9 to 5.1, This study replicates the association between R47H and Alzheimer's disease risk in a large, population-based sample, and estimates the population frequency and attributable risk of this rare variant, Moreover, mutation scanning of the five exons of TREM2 failed to detect the presence of novel polymorphisms, A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland, We also found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer's disease had poorer cognitive function than noncarriers, Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease through impaired containment of inflammatory processes, rs75932628-T variant of the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has recently been identified as a rare risk factor for late-onset Alzheimer's disease (AD), These results confirm the association between this variant and AD and underline its involvement in early-onset cases, recent studies have reported the association of rs75932628-T in the TREM2 gene with the risk for Alzheimer's disease (AD), Rs75932628-T is a rare nonsynonymous variant (p.R47H) that confers a high risk of AD with an effect size similar to that of the APOE ɛ4 allele, Here, we report the first positive replication study in a Spanish population and confirm that TREM2 rs75932628-T is associated with the risk for AD, works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD), with an odds ratio similar to that of the apolipoprotein E ε4 allele, The reduced function of TREM2 was speculated to be the main cause in the pathogenic effects of this risk variant, and TREM2 is highly expressed in white matter, as well as in the hippocampus and neocortex, which is partly consistent with the pathological features reported in AD brain, indicating the possible involvement of TREM2 in AD pathogenesis, Emerging evidence has demonstrated that TREM2 could suppress inflammatory response by repression of microglia-mediated cytokine production and secretion, which may prevent inflammation-induced bystander damage of neurons, TREM2 also participates in the regulation of phagocytic pathways that are responsible for the removal of neuronal debris, Based on the potential protective actions of TREM2 in AD pathogenesis, targeting TREM2 might provide new opportunities for AD treatment, Under the hypothesis that low-prevalence variants showing moderate-to-high effect size may be associated with risk for sAD, two independent research groups have demonstrated that a rare variant (rs75932628, encoding a substitution of arginine by histidine at residue 47 (R47H), in the TREM2 gene, which encodes the triggering receptor expressed on myeloid cells 2) is significantly associated with an increased susceptibility to sAD, Recently, a novel variant in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has been identified that has refocused the spotlight back onto inflammation as a major contributing factor in AD, TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk, evidence suggests that rare genetic variants within the TREM2 gene are associated with increased risk of Alzheimer's disease, These data suggest that a mutational burden in TREM2 may serve as a risk factor for neurodegenerative disease in general, and that potentially this class of TREM2 variant carriers with dementia should be considered as having a molecularly distinct form of neurodegenerative disease, The association of TREM2 variants with AD brings innate immune signaling into the light, affirming innate immunity's role as a significant factor in AD pathogenesis, The purpose of this paper is to discuss these recent developments including the potential role that TREM2 normally plays and how loss of function may contribute to AD pathogenesis by enhancing oxidative stress and inflammation within the CNS, Even though we are more at the beginning than at the end of sAD genetics, there is some reason for optimism given the recent identification of novel risk or protective variants (such as rare TREM2 and APP mutations) showing strong statistical associations with sAD[SEP]Relations: TREM2 has relations: disease_protein with Alzheimer disease, disease_protein with Alzheimer disease, disease_protein with dementia (disease), disease_protein with dementia (disease), disease_protein with semantic dementia, disease_protein with semantic dementia, disease_protein with frontotemporal dementia, disease_protein with frontotemporal dementia, disease_protein with dystonia, disease_protein with dystonia. Definitions: neocortex defined as following: The largest portion of the CEREBRAL CORTEX in which the NEURONS are arranged in six layers in the mammalian brain: molecular, external granular, external pyramidal, internal granular, internal pyramidal and multiform layers.. variant defined as following: An alteration or difference from a norm or standard.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. histidine defined as following: An essential amino acid that is required for the production of HISTAMINE.. sAD defined as following: A syndrome characterized by depressions that recur annually at the same time each year, usually during the winter months. Other symptoms include anxiety, irritability, decreased energy, increased appetite (carbohydrate cravings), increased duration of sleep, and weight gain. SAD (seasonal affective disorder) can be treated by daily exposure to bright artificial lights (PHOTOTHERAPY), during the season of recurrence.. APOE defined as following: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. myeloid cells defined as following: The classes of BONE MARROW-derived blood cells in the monocytic series (MONOCYTES and their precursors) and granulocytic series (GRANULOCYTES and their precursors).. TREM2 defined as following: Triggering receptor expressed on myeloid cells 2 (230 aa, ~25 kDa) is encoded by the human TREM2 gene. This protein plays a role in macrophage and dendritic cell immune responses.. allele defined as following: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.. region defined as following: The continents and countries situated on those continents; the UNITED STATES and each of the constituent states arranged by region; CANADA and each of its provinces; AUSTRALIA and each of its states; the major bodies of water and major islands on both hemispheres; and selected major cities.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. arginine defined as following: An essential amino acid that is physiologically active in the L-form.. FTD defined as following: The most common clinical form of FRONTOTEMPORAL LOBAR DEGENERATION, this dementia presents with personality and behavioral changes often associated with disinhibition, apathy, and lack of insight.. domain defined as following: A taxonomic category above that of Kingdom.. neurodegenerative disease defined as following: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.. polymorphisms defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.. TREM2 gene defined as following: This gene plays a role in the activation of immune responses.. dementia defined as following: The presence of dementia in an individual younger than age sixty five.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. exons defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.. gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. substitution defined as following:Definition: Indicates that the subject Act has undergone or should undergo substitution of a type indicated by Act.code.
Rationale: Used to specify \"allowed\" substitution when creating orders, \"actual\" susbstitution when sending events, as well as the reason for the substitution and who was responsible for it.
.", "label": "yes"} {"id": "converted_506", "sentence1": "Are there conserved noncoding elements identified between genomes of human and teleosts?", "sentence2": "We report evidence for a mechanism for the maintenance of long-range conserved synteny across vertebrate genomes. We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes, After whole genome duplication in teleosts, GRBs, including HCNEs and target genes, were often maintained in both copies, while bystander genes were typically lost from one GRB, strongly suggesting that evolutionary pressure acts to keep the single-copy GRBs of higher vertebrates intact. We show that loss of bystander genes and other mutational events suffered by duplicated GRBs in teleost genomes permits target gene identification and HCNE/target gene assignment, Vertebrate genomes contain thousands of conserved noncoding elements (CNEs) that often function as tissue-specific enhancers. In this study, we have identified CNEs in human, dog, chicken, Xenopus, and four teleost fishes (zebrafish, stickleback, medaka, and fugu) using elephant shark, a cartilaginous vertebrate, as the base genome and investigated the evolution of these ancient vertebrate CNEs (aCNEs) in bony vertebrate lineages, This implicates the \"fish-specific\" whole-genome duplication in the accelerated evolution and the loss of a large number of both copies of duplicated CNEs in teleost fishes, We found zebrafish conserved noncoding elements (CNEs) with pan-vertebrate as well as fish-specific orthologous sequences from across 200 kb of the zebrafish fgf8a genomic regulatory block to direct reporter expression in patterns consistent with the expression pattern of fgf8a, A significant number of conserved noncoding elements (CNEs) shared between cartilaginous fishes and tetrapods have diverged beyond recognition in teleost fishes. The divergence of CNEs seems to have been initiated in basal ray-finned fishes before the WGD. The fast evolving singleton and duplicated genes as well as the divergent CNEs might have contributed to the diversity of teleost fishes, We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes., Ancient vertebrate conserved noncoding elements have been evolving rapidly in teleost fishes., A significant number of conserved noncoding elements (CNEs) shared between cartilaginous fishes and tetrapods have diverged beyond recognition in teleost fishes., We have used a transposon-based transgenic assay in zebrafish to evaluate noncoding sequences at the zebrafish ret locus, conserved among teleosts, and at the human RET locus, conserved among mammals., Using computational analysis and exploiting the diversity of teleost genomes, we identified a cluster of highly conserved noncoding sequences surrounding the Six3 gene[SEP]Relations: vertebra has relations: anatomy_anatomy with non-transverse process-bearing vertebra, anatomy_anatomy with non-transverse process-bearing vertebra, anatomy_anatomy with vertebral element, anatomy_anatomy with vertebral element. familial acanthosis nigricans has relations: disease_disease with genetic skin disease, disease_disease with genetic skin disease, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance. anterior cutaneous nerve entrapment syndrome has relations: disease_phenotype_positive with Allodynia, disease_phenotype_positive with Allodynia. Definitions: dog defined as following: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065). cartilaginous fishes defined as following: fish with lateral fins, gills in separate gill clefts, skin covered with placoid scales, cartilaginous skeleton, no bone present and spriacles connecting to pharynx; most are marine.. zebrafish defined as following: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research.. fishes defined as following: A group of cold-blooded, aquatic vertebrates having gills, fins, a cartilaginous or bony endoskeleton, and elongated bodies covered with scales.. medaka defined as following: Common name for a species in the genus Oryzias.. vertebrate defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes.. stickleback defined as following: Common name for fish found mostly in the family Gasterosteidae. The three-spine stickleback (Gasterosteus aculeatus) is frequently studied.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. aCNEs defined as following: A chronic neuropathic pain syndrome of the abdominal wall caused by entrapment of anterior cutaneous branches of 7 to 12th intercostal nerves along the lateral border of the anterior rectus abdominis fascia.. Six3 gene defined as following: This gene plays a role in retinal development.. fugu defined as following: A genus of pufferfish commonly used for research.. Xenopus defined as following: The commonest and widest ranging species of the clawed \"frog\" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.. GRB defined as following: Human GZMB wild-type allele is located in the vicinity of 14q11.2 and is approximately 3 kb in length. This allele, which encodes granzyme B protein, is involved in both proteolysis and cellular immune responses.. mammals defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. human defined as following: Members of the species Homo sapiens.. genomes defined as following: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA..", "label": "yes"} {"id": "converted_2662", "sentence1": "Does oncogene-induced DNA replication stress inhibit genomic instability?", "sentence2": "Oncogene-induced DNA replication stress is thought to drive genomic instability in cancer., We propose that single-stranded DNA generated in response to oncogene-induced replication stress compromises the repair of deaminated cytosines and other damaged bases, leading to the observed SNS mutator phenotype.[SEP]Relations: malignant ear neoplasm has relations: disease_disease with head and neck cancer, disease_disease with head and neck cancer, disease_disease with middle ear cancer, disease_disease with middle ear cancer, disease_disease with inner ear cancer, disease_disease with inner ear cancer, disease_disease with external ear cancer, disease_disease with external ear cancer, disease_disease with ear neoplasm, disease_disease with ear neoplasm. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. SNS defined as following: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system..", "label": "no"} {"id": "converted_1861", "sentence1": "Is treatment resistant depression related to vitamin B9?", "sentence2": "Suboptimal serum and red blood cell folate levels have been associated with a poorer response to antidepressant therapy, a greater severity of symptoms, later onset of clinical improvement, and overall treatment resistance. This article reviews the evidence for L-methylfolate and folic acid as antidepressive agents in depression and discusses their clinical use, Although further randomized controlled trials in this area appear warranted, SAMe and L-methylfolate may represent a useful addition to the AD armamentarium., Patients with depression have consistently been found to have lower levels of serum and red blood cell folate than normal or nondepressed psychiatric patients. Decreased folate levels have been associated with lowered response rates to standard antidepressant pharmacotherapy. Recent studies have shown that augmentation with a folate supplement increases medication response in both treatment-naïve and treatment-resistant depressed patients irrespective of whether there is folate deficiency., Depressed patients with both low and normal folate levels may benefit from augmenting a primary antidepressant medication either initially, at the onset of treatment, or later after some degree of treatment resistance has been recognized., The results of this study suggest that intake of vitamin B9 may modulate the total score of Center for Epidemiological Studies Depression Scale (CES-D) and two subscales of the CES-D including depressive affect and interpersonal difficulties., The results of this study suggest that intake of vitamin B9 may modulate the total score of Center for Epidemiological Studies Depression Scale (CES-D) and two subscales of the CES-D including depressive affect and interpersonal difficulties. , This article reviews the metabolic and clinical importance of folate, vitamin B12, and SAMe, as well as clinical trials in relation to depression and dementia, In particular, vitamins B1, B3, B6, B9 and B12 are essential for neuronal function and deficiencies have been linked to depression.[SEP]Relations: Folic acid has relations: drug_drug with Amphotericin B, drug_drug with Amphotericin B, contraindication with diabetes mellitus (disease), contraindication with diabetes mellitus (disease), drug_drug with Blonanserin, drug_drug with Blonanserin, drug_drug with Brincidofovir, drug_drug with Brincidofovir. Thiamine has relations: drug_protein with SLC19A2, drug_protein with SLC19A2. Definitions: folate defined as following: A cofactor for 1-carbon transfer involved with DNA synthesis.. SAMe defined as following: Physiologic methyl radical donor involved in enzymatic transmethylation reactions and present in all living organisms. It possesses anti-inflammatory activity and has been used in treatment of chronic liver disease. (From Merck, 11th ed). red blood cell folate defined as following: The determination of the concentration of folic acid present in a sample of red blood cells.. folic acid defined as following: A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.. antidepressant defined as following: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.. L-methylfolate defined as following: A nutritional supplement containing the biologically active form of the B9 vitamin folate, 5-methyltetrahydrofolate (L-methylfolate), with potential antineoplastic activity. Upon administration, L-methylfolate is able to provide methyl groups allowing an increase in the level of DNA methylation in the promoter regions of certain tumor-promoting genes, thereby reversing the DNA hypomethylation of these genes and inactivating them. This may result in a decrease of both tumor cell proliferation and tumor progression. In addition, administration of L-methylfolate may sensitize tumor cells to the cytotoxic effects of other chemotherapeutic agents. Unlike folic acid, L-methylfolate is able to cross the blood brain barrier and could be beneficial in the treatment of brain tumors. DNA hypomethylation of certain genes leads to chromosome instability and contributes to tumor development.. dementia defined as following: The presence of dementia in an individual younger than age sixty five.. vitamins B1 defined as following: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2- hydroxyethyl)-4-methylthiazolium chloride.. vitamin B9 defined as following: A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia..", "label": "yes"} {"id": "converted_3269", "sentence1": "Is Li–Fraumeni syndrome a rare, autosomal recessive, hereditary disorder that predisposes carriers to cancer development?", "sentence2": "Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome inherited in an autosomal dominant fashion that involves a germline mutation of tumor protein 53 (TP53). , Li-Fraumeni syndrome (LFS), a multiorgan cancer predisposition caused by germline TP53 mutations, confers significant cancer risks for young people (15-39 years). Yet evidence of how individuals experience this condition and the psychosocial implications are lacking. Therefore, this systematic review assessed the psychosocial implications of living with, or at risk of, an autosomal dominant condition as a young person, to, Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disorder caused by a mutation in the p53 gene., Li-Fraumeni syndrome (LFS) is an autosomal dominant disorder occurring at a young age that predisposes individuals to multiple forms of cancer and to a heterogeneous spectrum of malignancies., Li-Fraumeni syndrome (LFS) is a rare hereditary autosomal dominant cancer disorder., Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer disorder., Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary cancer predisposition disorder., Li-Fraumeni syndrome is a rare autosomal dominant cancer predisposition syndrome., Li-Fraumeni syndrome is an autosomal dominant disorder that is characterized by various types of cancer in childhood and adult cases., Li-Fraumeni syndrome (LFS) is a rare hereditary cancer syndrome associated with an autosomal dominant mutation inheritance in the TP53 tumor suppressor gene and a wide spectrum of cancer diagnoses., The Li-Fraumeni syndrome is an autosomal dominant disorder characterized by a high risk of developing osteosarcoma and has been found in up to 3% of children with osteosarcoma., Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary cancer predisposition disorder., Li-Fraumeni syndrome (LFS) is an inherited, autosomal-dominant condition that predisposes individuals to a wide-spectrum of tumors at an early age., The Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary disorder associated with different tumor types in childhood and young adults.[SEP]Relations: Li-Fraumeni syndrome has relations: disease_disease with autosomal dominant disease, disease_disease with autosomal dominant disease, disease_disease with autosomal dominant disease, disease_disease with autosomal dominant disease, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance. autosomal dominant disease has relations: disease_disease with Li-Fraumeni syndrome, disease_disease with Li-Fraumeni syndrome. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. p53 gene defined as following: Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.. autosomal dominant defined as following: A rare distal arthrogryposis syndrome with characteristics of multiple pterygia (typically involving the neck, axilla and popliteal areas), joint contractures, ptosis, camptodactyly of the hands with hypoplastic flexion creases, vertebral fusions, severe scoliosis and short stature. There is evidence this disease is caused by heterozygous mutation in the MYH3 gene on chromosome 17p13.. LFS defined as following: Rare autosomal dominant syndrome characterized by mesenchymal and epithelial neoplasms at multiple sites. MUTATION of the p53 tumor suppressor gene, a component of the DNA DAMAGE response pathway, apparently predisposes family members who inherit it to develop certain cancers. The spectrum of cancers in the syndrome was shown to include, in addition to BREAST CANCER and soft tissue sarcomas (SARCOMA); BRAIN TUMORS; OSTEOSARCOMA; LEUKEMIA; and ADRENOCORTICAL CARCINOMA.. TP53 defined as following: Human TP53 wild-type allele is located in the vicinity of 17p13.1 and is approximately 19 kb in length. This allele, which encodes cellular tumor antigen p53 protein, plays a role in cell cycle regulation during the G0/G1transition. Alterations of the TP53 gene occur as both somatic and germline mutations in human malignancies in select cancer-prone families with Li-Fraumeni syndrome.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. osteosarcoma defined as following: A usually aggressive malignant bone-forming mesenchymal neoplasm arising from the bone. It may arise de novo or from a pre-existing lesion of the bone. Pain and a palpable mass are the most frequent clinical sign and symptom. It may spread to other anatomic sites, particularly the lungs.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. Li-Fraumeni syndrome defined as following: An autosomal dominant cancer predisposition syndrome caused by germline mutations of the CHEK2 gene. It is associated with breast carcinoma, gastric carcinoma, colorectal carcinoma, thyroid gland carcinoma, kidney carcinoma, prostate carcinoma, and non-Hodgkin lymphoma.. autosomal dominant disorder defined as following: An inherited disorder that manifests when one copy of a mutated gene is present.. malignancies defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. hereditary cancer syndrome defined as following: The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.. autosomal defined as following: Any chromosome other than a sex chromosome. [GOC:mah]. hereditary disorder defined as following: Genetic diseases are diseases in which inherited genes predispose to increased risk. The genetic disorders associated with cancer often result from an alteration or mutation in a single gene. The diseases range from rare dominant cancer family syndrome to familial tendencies in which low-penetrance genes may interact with other genes or environmental factors to induce cancer. Research may involve clinical, epidemiologic, and laboratory studies of persons, families, and populations at high risk of these disorders.. autosomal recessive defined as following: A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). [HPO:probinson].", "label": "no"} {"id": "converted_2101", "sentence1": "Is Obeticholic Acid used for treatment of Primary Biliary Cholangitis?", "sentence2": "Obeticholic acid in primary biliary cholangitis., In a double-blind, randomized, placebo-controlled study including 217 patients with primary biliary cholangitis, the authors show that obeticholic acid (a potent farnesoid X agonist) administered with ursodeoxycholic acid or as monotherapy significantly decreases serum alkaline phosphatase and bilirubin when compared to placebo., Obeticholic acid (Ocaliva(TM)) is a farnesoid-X receptor (FXR) agonist that is being developed by Intercept Pharmaceuticals for the treatment of various liver diseases, and has recently been granted accelerated approval in the USA for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to ursodeoxycholic acid, or as monotherapy in adults unable to tolerate ursodeoxycholic acid. , Obeticholic Acid (OCA) is a farnesoid X receptor (FXR) agonist which has been evaluated as a second line therapy in PBC and has recently been licenced by the FDA., OCA will be the first stratified therapy introduced in PBC, however confirmatory trial and real life data are needed to confirm that suggestive biochemical improvements are matched by improvement in key clinical outcomes., Obeticholic acid for the treatment of primary biliary cholangitis in adult patients: clinical utility and patient selection., A series of clinical trials of OCA in PBC, primarily in combination with UDCA, have established that OCA leads to significant reductions in serum alkaline phosphatase that are predicted to lead to improved clinical outcomes, while dose-dependent pruritus has been the most common adverse effect. On the basis of these studies, OCA was given conditional approval by the US Food and Drug Administration with plans to establish the long-term clinical efficacy of OCA in patients with advanced PBC., Although obeticholic acid was approved by the FDA for the treatment of PBC in May 2016, this development occurred after the symposium presentation. , While several agents are being studied in combination with UDCA, monotherapy with the novel agent obeticholic acid, a farnesoid X receptor agonist, has also shown promising results., Obeticholic acid (Ocaliva(TM)) is a farnesoid-X receptor (FXR) agonist that is being developed by Intercept Pharmaceuticals for the treatment of various liver diseases, and has recently been granted accelerated approval in the USA for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults with an inadequate response to ursodeoxycholic acid, or as monotherapy in adults unable to tolerate ursodeoxycholic acid., Obeticholic acid for the treatment of primary biliary cholangitis., Long-term clinical impact and cost-effectiveness of obeticholic acid for the treatment of primary biliary cholangitis., A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis., This article summarizes the milestones in the development of obeticholic acid leading to this first approval for primary biliary cholangitis., Obeticholic acid for the treatment of primary biliary cholangitis., Long-term Clinical Impact and Cost-Effectiveness of Obeticholic Acid for the Treatment of Primary Biliary Cholangitis., Obeticholic acid in primary biliary cholangitis., A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis., This article summarizes the milestones in the development of obeticholic acid leading to this first approval for primary biliary cholangitis.[SEP]Relations: primary biliary cholangitis has relations: contraindication with Cholic Acid, contraindication with Cholic Acid, contraindication with Fenofibric acid, contraindication with Fenofibric acid, contraindication with Chenodeoxycholic acid, contraindication with Chenodeoxycholic acid, contraindication with Fenofibrate, contraindication with Fenofibrate. Obeticholic acid has relations: drug_drug with Cholic Acid, drug_drug with Cholic Acid. Definitions: agonist defined as following: An agent that has affinity for a receptor and intrinsic activity at that receptor.. farnesoid X receptor defined as following: This gene is involved in bile acid binding and metabolism.. ursodeoxycholic acid defined as following: An epimer of chenodeoxycholic acid. It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic.. PBC defined as following: An autoimmune inflammatory disorder characterized by destruction of the small intrahepatic bile ducts. It affects predominantly females and it may lead to cirrhosis and liver failure. Patients have antimitochondrial and antinuclear antibodies in the peripheral blood.. Obeticholic acid defined as following: An orally bioavailable semi-synthetic bile acid derivative and an agonist of the nuclear bile acid receptor farnesoid X receptor (FXR) that may be used to lower hepatic exposure to bile acids. Upon oral administration, obeticholic acid targets and binds to FXR expressed in the liver and intestine, activating FXR-mediated bile acid, inflammatory, fibrotic, and metabolic pathways. This suppresses the production of bile acid in the hepatocytes and increases bile acid transport out of the hepatocytes, thereby reducing hepatic exposure to bile acids. FXR plays an important role in bile acid homeostasis and is involved in hepatic and intestinal inflammation and liver fibrosis.. FXR defined as following: Human NR1H4 wild-type allele is located in the vicinity of 12q23.1 and is approximately 91 kb in length. This allele, which encodes bile acid receptor protein, plays a role in both the metabolism of bile acids and ligand-dependent transcriptional regulation.. serum alkaline phosphatase defined as following: A quantitative measurement of the amount of alkaline phosphatase present in a sample of serum.. Obeticholic Acid defined as following: An orally bioavailable semi-synthetic bile acid derivative and an agonist of the nuclear bile acid receptor farnesoid X receptor (FXR) that may be used to lower hepatic exposure to bile acids. Upon oral administration, obeticholic acid targets and binds to FXR expressed in the liver and intestine, activating FXR-mediated bile acid, inflammatory, fibrotic, and metabolic pathways. This suppresses the production of bile acid in the hepatocytes and increases bile acid transport out of the hepatocytes, thereby reducing hepatic exposure to bile acids. FXR plays an important role in bile acid homeostasis and is involved in hepatic and intestinal inflammation and liver fibrosis.. Primary Biliary Cholangitis defined as following: An autoimmune inflammatory disorder characterized by destruction of the small intrahepatic bile ducts. It affects predominantly females and it may lead to cirrhosis and liver failure. Patients have antimitochondrial and antinuclear antibodies in the peripheral blood..", "label": "yes"} {"id": "converted_1804", "sentence1": "Is RASA2 involved in melanoma?", "sentence2": "Analysis of 501 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas. Recurrent loss-of-function mutations in RASA2 were found to increase RAS activation, melanoma cell growth and migration. RASA2 expression was lost in ≥30% of human melanomas and was associated with reduced patient survival. These findings identify RASA2 inactivation as a melanoma driver and highlight the importance of RasGAPs in cancer., Analysis of 501 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas, These findings identify RASA2 inactivation as a melanoma driver and highlight the importance of RasGAPs in cancer., Recurrent loss-of-function mutations in RASA2 were found to increase RAS activation, melanoma cell growth and migration., Analysis of 501 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of melanomas.[SEP]Relations: melanoma has relations: disease_protein with RASA2, disease_protein with RASA2, disease_protein with RAC2, disease_protein with RAC2, disease_protein with ARL2, disease_protein with ARL2, disease_protein with MDM2, disease_protein with MDM2, disease_protein with GPHA2, disease_protein with GPHA2. Definitions: melanoma defined as following: A benign or malignant, primary or metastatic neoplasm affecting the melanocytes.. cancer defined as following: A malignant tumor at the original site of growth.. RASA2 defined as following: Ras GTPase-activating protein 2 (850 aa, ~97 kDa) is encoded by the human RASA2 gene. This protein is involved in the activation of Ras p21 GTPases.. human defined as following: Members of the species Homo sapiens.. melanomas defined as following: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445). RasGAP defined as following: Human RASA2 wild-type allele is located in the vicinity of 3q23 and is approximately 128 kb in length. This allele, which encodes Ras GTPase-activating protein 2, plays a role in regulation of Ras-dependent signaling. Mutation of the gene may be associated with Noonan syndrome.. RAS defined as following: A family of oncogenes that are highly homologous with the retrovirus-associated DNA sequences (ras) originally isolated from Harvey and Kirsten murine sarcoma viruses. Mutated or overexpressed forms of the human ras genes are associated with constitutive ras GTPase activity, increased cellular proliferation, and cell transformation..", "label": "yes"} {"id": "converted_967", "sentence1": "Are CTCF and BORIS involved in genome regulation and cancer?", "sentence2": "CTCF is ubiquitously expressed and plays diverse roles in gene regulation, imprinting, insulation, intra/interchromosomal interactions, nuclear compartmentalisation, and alternative splicing. CTCF has a single paralogue, the testes-specific CTCF-like gene (CTCFL)/BORIS. CTCF and BORIS can be deregulated in cancer. The tumour suppressor gene CTCF can be mutated or deleted in cancer, or CTCF DNA binding can be altered by epigenetic changes. BORIS is aberrantly expressed frequently in cancer, leading some to propose a pro-tumourigenic role for BORIS. However, BORIS can inhibit cell proliferation, and is mutated in cancer similarly to CTCF suggesting BORIS activation in cancer may be due to global genetic or epigenetic changes typical of malignant transformation, The investigation of the molecular mechanisms engaged by CTCF to modulate tumor-related genes emphasizes the cell-type dependency of its tumor suppressor role. Indeed, the ability of CTCF to bind their promoters strictly depends by cell-type features as DNA methylation, BORIS-binding and post-translational modifications as PARYlation, Moreover, reduction of CTCF in normally BORIS-negative human fibroblasts resulted in derepression of BORIS promoters. These results provide a mechanistic basis for understanding cancer-related associations between haploinsufficiency of CTCF and BORIS derepression, and between the lack of functional p53 and aberrant activation of BORIS, CTCF and BORIS in genome regulation and cancer., The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer., Collectively, these data indicate that reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter mediates epigenetic regulation of this CT gene in lung cancer cells, and suggest that induction of BORIS may be a novel strategy to augment immunogenicity of pulmonary carcinomas., BORIS is the only known paralog of CTCF, a gene intimately involved in genomic imprinting, chromatin insulation, and nuclear regulation., However, BORIS can inhibit cell proliferation, and is mutated in cancer similarly to CTCF suggesting BORIS activation in cancer may be due to global genetic or epigenetic changes typical of malignant transformation., We suggest that BORIS is likely tethering epigenetic machinery to a novel class of CTCF/BORIS 11ZF target sequences that mediate induction of cancer-testis genes., Unlike CTCF, BORIS expression has been reported only in the testis and certain malignancies, leading to its classification as a \"cancer-testis\" antigen.[SEP]Relations: testis has relations: anatomy_protein_present with CTCF, anatomy_protein_present with CTCF, anatomy_protein_present with CTCFL, anatomy_protein_present with CTCFL, anatomy_protein_present with BNC1, anatomy_protein_present with BNC1. Geneticin has relations: drug_drug with Cefsulodin, drug_drug with Cefsulodin. Protein S human has relations: drug_drug with Cefsulodin, drug_drug with Cefsulodin. Definitions: gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. cancer defined as following: A malignant tumor at the original site of growth.. CTCF defined as following: CCN family member 2 (349 aa, ~38kDa) is encoded by the human CCN2 gene. This protein plays a role in the promotion of proliferation and differentiation of chondrocytes and also mediates heparin- and divalent cation-dependent cell adhesion in many different cell types.. promoters defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. p53 defined as following: Human TP53 wild-type allele is located in the vicinity of 17p13.1 and is approximately 19 kb in length. This allele, which encodes cellular tumor antigen p53 protein, plays a role in cell cycle regulation during the G0/G1transition. Alterations of the TP53 gene occur as both somatic and germline mutations in human malignancies in select cancer-prone families with Li-Fraumeni syndrome.. BORIS defined as following: Human CTCFL wild-type allele is located in the vicinity of 20q13.31 and is approximately 30 kb in length. This allele, which encodes transcriptional repressor CTCFL protein, is involved in both gene regulation and X-chromosome inactivation.. tumour suppressor gene defined as following: Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.. NY-ESO-1 defined as following: Human CTAG1A wild-type allele is located in the vicinity of Xq28 and is approximately 2 kb in length. This allele, which encodes cancer/testis antigen 1 protein, may play a role in both spermatogeneis and development of the testes. Aberrant expression of this gene is associated with incontinentia pigmenti.. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. mutated defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. testis defined as following: The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS.. malignancies defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas..", "label": "yes"} {"id": "converted_3994", "sentence1": "Is there an association of alterations in ADCY7 and ulcerative colitis?", "sentence2": "To further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, we sequenced the whole genomes of 4,280 patients at low coverage and compared them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing genome-wide association study cohorts and tested for association at ∼12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles the risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants and found that such variants explained little heritability. [SEP]Relations: ulcerative colitis (disease) has relations: disease_protein with ADCY7, disease_protein with ADCY7, disease_protein with IL7R, disease_protein with IL7R, disease_protein with IL1R2, disease_protein with IL1R2, disease_protein with IL23R, disease_protein with IL23R, disease_protein with CXCL8, disease_protein with CXCL8. Definitions: variants defined as following: An alteration or difference from a norm or standard.. ulcerative colitis defined as following: Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.. sequences defined as following: The sequence of nucleotide residues along a DNA chain.. inflammatory bowel diseases defined as following: Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS.. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. genomes defined as following: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA..", "label": "yes"} {"id": "converted_4558", "sentence1": "Do mutations in KCNT2 only cause phenotypes with epilepsy?", "sentence2": "KCNT2 variants resulting in substitutions affecting the Arg190 residue have been shown to cause epileptic encephalopathy and a recognizable facial gestalt. We report two additional individuals with intellectual disability, dysmorphic features, hypertrichosis, macrocephaly and the same de novo KCNT2 missense variants affecting the Arg190 residue as previously described. Notably, neither patient has epilepsy. Homology modeling of these missense variants revealed that they are likely to disrupt the stabilization of a closed channel conformation of KCNT2 resulting in a constitutively open state. This is the first report of pathogenic variants in KCNT2 causing a developmental phenotype without epilepsy.[SEP]Relations: epilepsy has relations: disease_protein with KCNT2, disease_protein with KCNT2, disease_protein with KCND2, disease_protein with KCND2, disease_protein with KCNAB2, disease_protein with KCNAB2, disease_protein with KCNA2, disease_protein with KCNA2, disease_protein with KCNQ2, disease_protein with KCNQ2. Definitions: variants defined as following: An alteration or difference from a norm or standard.. epilepsy defined as following: A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313). epileptic encephalopathy defined as following: A condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function. Epileptic encephalaopathy is characterized by (1) electrographic EEG paroxysmal activity that is often aggressive, (2) seizures that are usually multiform and intractable, (3) cognitive, behavioral and neurological deficits that may be relentless, and (4) sometimes early death. [PMID:21590624, PMID:23213494]. hypertrichosis defined as following: Excessive hair growth at inappropriate locations, such as on the extremities, the head, and the back. It is caused by genetic or acquired factors, and is an androgen-independent process. This concept does not include HIRSUTISM which is an androgen-dependent excess hair growth in WOMEN and CHILDREN.. macrocephaly defined as following: A congenital abnormality in which the occipitofrontal circumference is greater than two standard deviations above the mean for a given age. It is associated with HYDROCEPHALUS; SUBDURAL EFFUSION; ARACHNOID CYSTS; or is part of a genetic condition (e.g., ALEXANDER DISEASE; SOTOS SYNDROME).. intellectual disability defined as following: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28). mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "no"} {"id": "converted_766", "sentence1": "Does GC content vary markedly within a given isochore?", "sentence2": "The isochore, a large DNA sequence with relatively small GC variance, is one of the most important structures in eukaryotic genomes., Isochores are large regions of relatively homogeneous nucleotide composition, Vertebrate genomes are comprised of isochores that are relatively long (>100 kb) regions with a relatively homogenous (either GC-rich or AT-rich) base composition and with rather sharp boundaries with neighboring isochores., The human genome is composed of large sequence segments with fairly homogeneous GC content, namely isochores, Isochores, i.e. stretches of DNA with a distinct sequence composition and thus a specific GC content, The human genome is composed of long stretches of DNA with distinct GC contents, called isochores or GC-content domains., The human genome is divided into isochores, large stretches (>>300 kb) of genomic DNA with more or less consistent GC content. , Many eukaryotic genomes contain isochore regions, mosaics of homogeneous GC content that can abruptly change from one neighboring isochore to the next., One of the most striking features of mammalian and birds chromosomes is the variation in the guanine-cytosine (GC) content that occurs over scales of hundreds of kilobases to megabases; this is known as the \"isochore\" structure., The segmentation analysis shows that there are stronger indications of GC content changes at isochore borders than within an isochore., This partitioning is a natural one, since large-scale compositional properties vary much more among isochores than within them., This partitioning is a natural one, since large-scale compositional properties vary much more among isochores than within them., An isochore sequence may pass a homogeneity test when GC content fluctuations at smaller length scales are ignored or averaged out., This partitioning is a natural one, since large-scale compositional properties vary much more among isochores than within them[SEP]Relations: neoplastic syndrome has relations: disease_disease with ectopic ACTH secretion syndrome, disease_disease with ectopic ACTH secretion syndrome, disease_disease with Carney triad, disease_disease with Carney triad, disease_disease with ectopic hormone secretion syndrome associated with neoplasia, disease_disease with ectopic hormone secretion syndrome associated with neoplasia, disease_disease with mosaic variegated aneuploidy syndrome, disease_disease with mosaic variegated aneuploidy syndrome, disease_disease with Meigs syndrome, disease_disease with Meigs syndrome. Definitions: genomic DNA defined as following: The DNA that is part of the normal chromosomal complement of an organism.. DNA sequence defined as following: The sequence of nucleotide residues along a DNA chain.. Isochores defined as following: Large regions of the GENOME that contain local similarities in BASE COMPOSITION.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young..", "label": "no"} {"id": "converted_4315", "sentence1": "Is Keutel syndrome a common genetic disorder?", "sentence2": "Keutel syndrome (OMIM 245150) is a very rare syndrome , Keutel syndrome is a rare autosomal-recessive condition characterized by abnormal cartilage calcification., MGP-deficiency in humans leads to Keutel syndrome, a rare genetic disease hallmarked by abnormal soft tissue calcification. [SEP]Relations: LADD syndrome has relations: disease_disease with EEC syndrome and related syndrome, disease_disease with EEC syndrome and related syndrome, disease_disease with autosomal dominant disease, disease_disease with autosomal dominant disease, disease_disease with genetic otorhinolaryngological malformation, disease_disease with genetic otorhinolaryngological malformation, disease_disease with genetic multiple congenital anomalies/dysmorphic syndrome without intellectual disability, disease_disease with genetic multiple congenital anomalies/dysmorphic syndrome without intellectual disability, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance. Definitions: humans defined as following: Members of the species Homo sapiens.. Keutel syndrome defined as following: Osteoarticular abnormalities, highly arched palate, anorchia, and subnormal motor and mental development.. genetic disorder defined as following: Genetic diseases are diseases in which inherited genes predispose to increased risk. The genetic disorders associated with cancer often result from an alteration or mutation in a single gene. The diseases range from rare dominant cancer family syndrome to familial tendencies in which low-penetrance genes may interact with other genes or environmental factors to induce cancer. Research may involve clinical, epidemiologic, and laboratory studies of persons, families, and populations at high risk of these disorders..", "label": "no"} {"id": "converted_2955", "sentence1": "Are Copy Number Variants (CNVs) depleted in regions of low mappability?", "sentence2": "Human copy number variants are enriched in regions of low mappability., Applying PopSV to 640 human genomes, we find that low-mappability regions are approximately 5 times more likely to harbor germline CNVs, in stark contrast to the nearly uniform distribution observed for somatic CNVs in 95 cancer genomes. In addition to known enrichments in segmental duplication and near centromeres and telomeres, we also report that CNVs are enriched in specific types of satellite and in some of the most recent families of transposable elements. Finally, using this comprehensive approach, we identify 3455 regions with recurrent CNVs that were missing from existing catalogs. In particular, we identify 347 genes with a novel exonic CNV in low-mappability regions, including 29 genes previously associated with disease., Human copy number variants are enriched in regions of low mappability.Copy number variants (CNVs) are known to affect a large portion of the human genome and have been implicated in many diseases. [SEP]Relations: maintenance of DNA repeat elements has relations: bioprocess_bioprocess with maintenance of CRISPR repeat elements, bioprocess_bioprocess with maintenance of CRISPR repeat elements, bioprocess_protein with AXIN2, bioprocess_protein with AXIN2, bioprocess_protein with TCF7L2, bioprocess_protein with TCF7L2, bioprocess_protein with MSH2, bioprocess_protein with MSH2, bioprocess_protein with MSH3, bioprocess_protein with MSH3. Definitions: variants defined as following: An alteration or difference from a norm or standard.. Human defined as following: Members of the species Homo sapiens.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. transposable elements defined as following: Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.. telomeres defined as following: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs..", "label": "no"} {"id": "converted_4416", "sentence1": "Is periampullary carcinoma (PAC) a relatively rare genitourinary malignancy", "sentence2": "Pancreaticobiliary subtype of Periampullary carcinoma (PAC) has a poor prognosis in comparison to the intestinal subtype., MUC1, CK20, and CDX2 immunohistochemical markers can sub-classify periampullary carcinomas into pancreaticobiliary, intestinal, and mixed subtypes., Pancreaticoduodenectomy (PD) is a complex surgical procedure involving resection of the duodenum, the pancreatic head and uncinate process, and the distal common bile duct. It is most commonly performed for periampullary malignancy but may also be indicated in select cases of chronic pancreatitis or benign periampullary tumors., In patients suspected of pancreatic or periampullary cancer, abdominal contrast-enhanced computed tomography (CT) is the standard diagnostic modality., The pre-operative neutrophil-to-lymphocyte ratio (NLR), when ≥5 has been associated with reduced survival for patients with various gastrointestinal tract cancers, however, it's prognostic value in patients with periampullary tumour has not been reported to date., Comparison Of Biliary Stenting And Surgical Bypass In Palliative Management Of Irresectable Periampullary Carcinoma., Some 20-40% of the periampullary carcinoma is irresectable at the time of diagnosis. Biliary stenting and surgical bypass are commonly used palliative procedure., Whereas Periampulary AdenoCarcinoma (PAC) having four anatomic subtypes, pancreatic, Common Bile Duct (CBD), ampullary and duodenum shows relative better prognosis, DEFINITION: Periampullary carcinomas are rare and constitute a special entity, as diagnosed earlier and having a better prognosis than other duodenal tumors.METHODS: In the present study, we retrospectively reviewed the medical records of 16 patients with periampullary carcinomas over 10 years.RESULTS: 16 patients, 10 men and 6 women (median age 66.7 years, range 42-80) had a , Periampullary carcinomas: a special entity of duodenal tumors., Periampullary adenocarcinomas are rare neoplasm that originates from the pancreatic head, the ampulla of vater, the distal bile duct or the duodenum.[SEP]Relations: periampullary adenocarcinoma has relations: disease_disease with ampulla of vater adenocarcinoma, disease_disease with ampulla of vater adenocarcinoma. intestine has relations: anatomy_protein_present with PACS2, anatomy_protein_present with PACS2, anatomy_protein_present with PACS1, anatomy_protein_present with PACS1, anatomy_protein_present with PACSIN2, anatomy_protein_present with PACSIN2. duodenum has relations: anatomy_protein_present with PACS1, anatomy_protein_present with PACS1. Definitions: pancreatic head defined as following: That portion of the pancreas lying in the concavity of the duodenum.. MUC1 defined as following: Human MUC1 wild-type allele is located within 1q21 and is approximately 121 kb in length. This allele, which encodes mucin-like protein 1, plays a role in both cellular defense by binding pathogens and in cell signaling.. PD defined as following: A score of 4 or 5 on a 5-point PET scale with an increase in intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment.. gastrointestinal tract cancers defined as following: A primary or metastatic malignant neoplasm involving any part of the digestive system.. CK20 defined as following: Human KRT20 wild-type allele is located in the vicinity of 17q21.2 and is approximately 9 kb in length. This allele, which encodes keratin, type I cytoskeletal 20 protein, is involved in the modulation of intestinal development.. pancreatic defined as following: Peptide hormones secreted into the blood by cells in the ISLETS OF LANGERHANS of the pancreas. The alpha cells secrete glucagon; the beta cells secrete insulin; the delta cells secrete somatostatin; and the PP cells secrete pancreatic polypeptide.. intestinal defined as following: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.. CT defined as following: Tomography using x-ray transmission and a computer algorithm to reconstruct the image..", "label": "no"} {"id": "converted_3959", "sentence1": "Are PDXK mutations linked to polyneuropathy?", "sentence2": "PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation., To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy.METHODS: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification.RESULTS: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5'-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization.INTERPRETATION: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225-240., RETATION: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We sh, PDXK mutations cause polyneuropathy responsive to pyridoxal 5'-phosphate supplementation, Hereditary polyneuropathy with optic atrophy due to PDXK variant leading to impaired Vitamin B6 metabolism, INTERPRETATION: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP., RESULTS: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy., show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We[SEP]Relations: polyneuropathy has relations: disease_disease with polyneuropathy due to drug, disease_disease with polyneuropathy due to drug, disease_disease with peripheral neuropathy, disease_disease with peripheral neuropathy, disease_protein with PNPLA6, disease_protein with PNPLA6, disease_disease with idiopathic progressive polyneuropathy, disease_disease with idiopathic progressive polyneuropathy, disease_disease with polyneuritis, disease_disease with polyneuritis. Definitions: variants defined as following: An alteration or difference from a norm or standard.. erythrocyte defined as following: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.. adenosine triphosphate defined as following: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.. recombinant protein defined as following: Proteins prepared by recombinant DNA technology.. PLP defined as following: This is the active form of VITAMIN B 6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (PYRIDOXAMINE).. neuropathies defined as following: A disorder affecting the cranial nerves or the peripheral nervous system. It manifests with pain, tingling, numbness, and muscle weakness. It may be the result of physical injury, toxic substances, viral diseases, diabetes, renal failure, cancer, and drugs.. polyneuropathy defined as following: Diseases of multiple peripheral nerves simultaneously. Polyneuropathies usually are characterized by symmetrical, bilateral distal motor and sensory impairment with a graded increase in severity distally. The pathological processes affecting peripheral nerves include degeneration of the axon, myelin or both. The various forms of polyneuropathy are categorized by the type of nerve affected (e.g., sensory, motor, or autonomic), by the distribution of nerve injury (e.g., distal vs. proximal), by nerve component primarily affected (e.g., demyelinating vs. axonal), by etiology, or by pattern of inheritance.. fatigue defined as following: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.. optic atrophy defined as following: Atrophy of the optic disk which may be congenital or acquired. This condition indicates a deficiency in the number of nerve fibers which arise in the RETINA and converge to form the OPTIC DISK; OPTIC NERVE; OPTIC CHIASM; and optic tracts. GLAUCOMA; ISCHEMIA; inflammation, a chronic elevation of intracranial pressure, toxins, optic nerve compression, and inherited conditions (see OPTIC ATROPHIES, HEREDITARY) are relatively common causes of this condition.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"} {"id": "converted_4514", "sentence1": "Do angiotensin-converting-enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) increase the likelihood of severe COVID-19?", "sentence2": "These findings suggest that the use of ACE-I and ARB is not associated with adverse outcomes and may be associated with improved outcomes in COVID-19, which is immediately relevant to care of the many patients on these medications., There are theoretical concerns that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could increase the risk of severe Covid-19., ACEIs and ARBs were associated with a slight reduction in Covid-19 hospitalization risk compared with treatment with other first-line antihypertensives (OR for ACEIs 0.95, 95% CI 0.92-0.98; OR for ARBs 0.94, 95% CI 0.90-0.97)., There were no meaningful differences in risk for ACEIs compared with ARBs., ACEIs and ARBs were not associated with an increased risk of Covid-19 hospitalization or with hospitalization involving ICU admission, invasive mechanical ventilation, or death., In patients with HTN and COVID-19, neither ACEi nor ARBs were independently associated with mortality., Our data confirm Specialty Societal recommendations, suggesting that treatment with ACEIs or ARBs should not be discontinued because of COVID-19., Random-effects meta-analysis showed ACEI/ARB treatment was significantly associated with a lower risk of mortality in hypertensive COVID-19 patients (odds ratio [OR] = 0.624, 95% confidence interval [CI] = 0.457-0.852, p = .003, I2 = 74.3%)., In addition, the ACEI/ARB treatment was associated with a lower risk of ventilatory support (OR = 0.682, 95% CI = 0.475-1.978, p = .037, I2 = 0.0%). In conclusion, these results suggest that ACEI/ARB medications should not be discontinued for hypertensive patients in the context of COVID-19 pandemic., Use of ACE-I or ARB medications was not associated with increased risk of hospitalization, intensive care unit admission, or death. Compared to patients with charted past medical history, there was a lower risk of hospitalization for patients on ACE-I (odds ratio (OR) 0.43; 95% confidence interval (CI) 0.19-0.97; P = 0.0426) and ARB (OR 0.39; 95% CI 0.17-0.90; P = 0.0270)., The second analysis showed that the use of ACEI and/or ARB did not affect in-hospital mortality (risk ratio [RR] 95% [CI]] = 0.88 [0.64-1.20], p = 0.42). The subgroup analysis by limiting studies of patients with hypertension showed ACEI and/or ARB use was associated with a significant reduction of in-hospital mortality compared with no ACEI or ARB use (RR [CI] = 0.66 [0.49-0.89], p = 0.004). Our analysis demonstrated that ACEI and/or ARB use was associated neither with testing positive rates of COVID-19 nor with mortality of COVID-19 patients., ACEIs/ARBs are protective factors against mortality in COVID-19 patients with HTN, and these agents can be considered potential therapeutic options in this disease., There has been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes., Although further research on the influence of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there are presently no compelling clinical data showing that ACEIs and ARBs increase the likelihood of contracting COVID-19 or worsen the outcome of SARS-CoV‑2 infections, There has been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes, ACEIs and ARBs do not promote a more severe outcome of COVID-19., Meta-analysis showed no significant increase in the risk of COVID-19 infection (odds ratio [OR]: 0.95, 95%CI: 0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR: 0.75, 95%CI: 0.59-0.96) and mortality (OR: 0.52, 95%CI: 0.35-0.79)., Subgroup analyses showed among the general population, ACEI/ARB therapy was associated with reduced severe COVID-19 infection (OR: 0.79, 95%CI: 0.60-1.05) and all-cause mortality (OR: 0.31, 95%CI: 0.13-0.75), and COVID-19 infection (OR: 0.85, 95% CI: 0.66-1.08) were not increased., On the basis of the available evidence, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients., Some studies of hospitalized patients suggested that the risk of death and/or severe illness due to COVID-19 is not associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor type 1 blockers (ARBs), Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID-19. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.[SEP]Relations: type 2 angiotensin receptor binding has relations: molfunc_protein with AGT, molfunc_protein with AGT. Protein S human has relations: drug_drug with Anti-inhibitor coagulant complex, drug_drug with Anti-inhibitor coagulant complex, drug_drug with Ardeparin, drug_drug with Ardeparin, drug_drug with Peginterferon alfa-2b, drug_drug with Peginterferon alfa-2b, drug_drug with Coagulation Factor IX (Recombinant), drug_drug with Coagulation Factor IX (Recombinant). Definitions: death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. ARB defined as following: A retinal dystrophy with characteristics of central visual loss in the first 2 decades of life, associated with an absent electrooculogram (EOG) light rise and a reduced electroretinogram (ERG). To date less than 20 cases have been described in the world literature. Caused by compound heterozygous or homozygous mutations in the BEST1 gene (11q12) which encodes the chloride ion channel bestrophin-1 (expressed in the retinal pigment epithelium (RPE)). Mutations in BEST1 reduce or abolish the activity of the channel. It has been proposed that ARB may represent the null phenotype of bestrophin-1 in humans. Transmission is autosomal recessive.. angiotensin receptor blockers defined as following: Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.. hypertension defined as following: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.. ACE2 defined as following: Angiotensin-converting enzyme 2 (805 aa, ~92 kDa) is encoded by the human ACE2 gene. This protein plays a role in both vasodilation and protein cleavage.. angiotensin-converting enzyme defined as following: A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of ANGIOTENSIN I to ANGIOTENSIN II, with increase in vasoconstrictor activity, but no action on angiotensin II. It is also able to inactivate BRADYKININ, a potent vasodilator; and has a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. (From https://www.uniprot.org April 15, 2020).. angiotensin II receptor type 1 blockers defined as following: Agents that antagonize the ANGIOTENSIN II TYPE 2 RECEPTOR.. illness defined as following: A state of ill health, bodily malfunction, or discomfort.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown..", "label": "no"} {"id": "converted_3753", "sentence1": "Is Bcl-2-like protein 1 an pro apoptotic protein?", "sentence2": "Extensively established key effectors of such apoptotic bypass mechanisms, the antiapoptotic BCL-2 (apoptosis regulator BCL-2) proteins, determine the response of cancer cells to chemotherapeutics, decreasing the expression of anti-apoptotic factors, including apoptosis regulator Bcl-2 and Bcl-2-like protein 1 in FaDu cells, Like many cancers, TNBC cells often deregulate programmed cell death by upregulating anti-apoptotic proteins of the B-cell CLL/lymphoma 2 (Bcl-2) family., anti-apoptotic Bcl-2-like protein 1 (BCL2L1, Bcl-xL) [SEP]Relations: Protein S human has relations: drug_protein with PROC, drug_protein with PROC, drug_drug with Cepeginterferon alfa-2B, drug_drug with Cepeginterferon alfa-2B, drug_drug with Peginterferon alfa-2b, drug_drug with Peginterferon alfa-2b. Protein C has relations: drug_drug with Peginterferon alfa-2b, drug_drug with Peginterferon alfa-2b, drug_drug with Epoprostenol, drug_drug with Epoprostenol. Definitions: Bcl-2 defined as following: The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.. BCL2L1 defined as following: A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS and is a regulatory subunit for PROTEIN PHOSPHATASE 1. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.. cancer cells defined as following: Cells of, or derived from, a malignant tumor.. Bcl-2-like protein 1 defined as following: Bcl-2-like protein 2 (193 aa, ~21 kDa) is encoded by the human BCL2L2 gene. This protein plays a role the regulation of apoptosis.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. B-cell CLL/lymphoma 2 defined as following: Apoptosis regulator Bcl-2 (239 aa, ~26 kDa) is encoded by the human BCL2 gene. This protein plays a role in cellular survival.. Bcl-2-like protein defined as following: Apoptosis regulator BAX (192 aa, ~21 kDa) is encoded by the human BAX gene. This protein plays a role in both apoptosis and protein-protein interactions..", "label": "no"} {"id": "converted_366", "sentence1": "Is there an association between TERT promoter mutation and survival of glioblastoma patients?", "sentence2": "Glioblastoma patients with TERT mutations showed a shorter survival than those without TERT mutations in univariate analysis (median, 9.3 vs. 10.5 months; P = 0.015) and multivariate analysis after adjusting for age and gender (HR 1.38, 95 % CI 1.01-1.88, P = 0.041). However, TERT mutations had no significant impact on patients' survival in multivariate analysis after further adjusting for other genetic alterations, or when primary and secondary glioblastomas were separately analysed. These results suggest that the prognostic value of TERT mutations for poor survival is largely due to their inverse correlation with IDH1 mutations, which are a significant prognostic marker of better survival in patients with secondary glioblastomas., Patients with tumors lacking hTERT expression/TA showed a significant survival benefit (Kaplan-Meier test, both P < .01), which, however, was based exclusively on the younger patient subgroup (≤60 y, both P < .005; >60 y, both ns). , Glioblastoma patients with TERT mutations showed a shorter survival than those without TERT mutations in univariate analysis (median, 9.3 vs[SEP]Relations: adult glioblastoma has relations: disease_disease with glioblastoma (disease), disease_disease with glioblastoma (disease), disease_disease with adult spinal cord glioblastoma, disease_disease with adult spinal cord glioblastoma, disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult infiltrating astrocytic neoplasm. Somatic mutation has relations: disease_phenotype_positive with glioma susceptibility, disease_phenotype_positive with glioma susceptibility, disease_phenotype_positive with retinoblastoma, disease_phenotype_positive with retinoblastoma. Definitions: genetic alterations defined as following: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.. IDH1 defined as following: Isocitrate dehydrogenase [NADP] cytoplasmic (414 aa, 47 kDa) is encoded by the human IDH1 gene. This protein plays a role the oxidation of isocitrate and oxalosuccinate.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. Glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO). HR defined as following: The rapid, localized death of plant cells in response to invasion by a pathogen. [ISBN:0582227089]. TERT defined as following: Human TERT wild-type allele is located in the vicinity of 5p15.33 and is approximately 42 kb in length. This allele, which encodes telomerase reverse transcriptase protein, is involved in the replication of telomeres. Aberrant expression of the allele at elevated levels may contribute to oncogenesis.. glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO).", "label": "yes"} {"id": "converted_818", "sentence1": "Is there evidence to suggest that triiodothyronine has neuroprotective properties in traumatic brain injury?", "sentence2": "Exogenous T3 administration provides neuroprotection in a murine model of traumatic brain injury., Treatment with T3 (1.2μg/100g body weight, i.p.) 1h after TBI resulted in a significant improvement in motor and cognitive recovery after CCI, as well as in marked reduction of lesion volumes. , Western blot analysis revealed the ability of T3 to reduce brain trauma through modulation of cytoplasmic-nuclear shuttling of nuclear factor-κB (NF-κB). Twenty-four hours after brain trauma, T3-treated mice also showed significantly lower number of TUNEL(+) apoptotic neurons and curtailed induction of Bax, compared to vehicle control. In addition, T3 significantly enhanced the post-TBI expression of the neuroprotective neurotrophins (BDNF and GDNF) compared to vehicle. , The stimulating effect of T3 on peripheral nerve regeneration may have considerable therapeutic potential., The present study provides evidence that the peripheral nervous system has its own system responsible for the local production of 3,5,3'-triiodothyronine, which may play a key role during the regeneration process., Although it has been hypothesized that T3 may facilitate neuronal regeneration after CNS injury, the 5'-D2 response to brain injury is unknown., The outcome after brain injury is closely correlated with the intensity of these changes, particularly with catecholamine plasma levels and the severity of the low triiodothyronine syndrome., The thyroid hormones triiodothyronine (T3) and L-thyroxine appear to enhance regeneration in the peripheral and central nervous system (CNS). , T3 treatment influenced the general levels of incorporation of all treated groups over all days postoperation., T3 effects appear to involve an increased sensitivity of the cells of the injured nervous system to the hormone., T3, when administered over an 8 week period, stimulated axonal regeneration in the dorsal cortex and corpus callosum and promoted healing of the wound in the corpus callosum. The results of this investigation suggest that the use of T3 in the clinical treatment of injury to the central nervous system may be of less value than the work of earlier authors had indicated., In addition, T3 significantly enhanced the post-TBI expression of the neuroprotective neurotrophins (BDNF and GDNF) compared to vehicle[SEP]Relations: brain injury has relations: contraindication with Propantheline, contraindication with Propantheline, contraindication with Propantheline, contraindication with Propantheline, contraindication with Pheniramine, contraindication with Pheniramine, contraindication with Pheniramine, contraindication with Pheniramine, contraindication with Homatropine, contraindication with Homatropine. Definitions: T3 defined as following: This gene plays a regulatory role in the production and utilization of ATP.. BDNF defined as following: A member of the nerve growth factor family of trophic factors. In the brain BDNF has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons. (From Kendrew, The Encyclopedia of Molecular Biology, 1994). GDNF defined as following: The founding member of the glial cell line-derived neurotrophic factor family. It was originally characterized as a NERVE GROWTH FACTOR promoting the survival of MIDBRAIN dopaminergic NEURONS, and it has been studied as a potential treatment for PARKINSON DISEASE.. peripheral defined as following: On or near an edge or constituting an outer boundary; the outer area.. traumatic brain injury defined as following: A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.. Bax defined as following: Apoptosis regulator BAX (192 aa, ~21 kDa) is encoded by the human BAX gene. This protein plays a role in both apoptosis and protein-protein interactions.. L-thyroxine defined as following: The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. brain injury defined as following: Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. murine defined as following: Any of numerous species of small rodents belonging to the genus Mus and various related genera of the family Muridae.. 3,5,3'-triiodothyronine defined as following: A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.. triiodothyronine defined as following: A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3..", "label": "yes"} {"id": "converted_2171", "sentence1": "Is tirilazad effective for treatment of aneurysmal subarachnoid haemorrhage?", "sentence2": "There was no significant difference between the two groups at the end of follow up for the primary outcome, death (odds ratio (OR) 0.89, 95% confidence interval (CI) 0.74 to 1.06), or in poor outcome (death, vegetative state or severe disability) (OR 1.04, 95% CI 0.90 to 1.21). During the treatment period, fewer patients developed delayed cerebral ischaemia in the tirilazad group than in the control group (OR 0.80, 95% CI 0.69 to 0.93). Subgroup analyses did not demonstrate any significant difference in effects of tirilazad on clinical outcomes. , AUTHORS' CONCLUSIONS: There is no evidence that tirilazad, in addition to nimodipine, reduces mortality or improves poor outcome in patients with aneurysmal SAH., This clinical trial suggest that tirilazad mesylate, at a dosage of 6 mg/kg/day, improves overall outcome in aneurysmal subarachnoid hemorrhage patients., Tirilazad is ineffective.There are many possible successful treatment options for preventing vasospasm, delayed ischemic neurologic deficits, and poor neurologic outcome following aneurysmal subarachnoid hemorrhage; however, further multicenter RCTs need to be performed to determine if there is a significant benefit from their use, Findings from previous multicenter clinical trials have suggested that tirilazad mesylate, a synthetic nonhormonal 21-aminosteroid, might be effective in preventing delayed cerebral ischemia following subarachnoid hemorrhage (SAH)., This clinical trial suggest that tirilazad mesylate, at a dosage of 6 mg/kg/day, improves overall outcome in aneurysmal subarachnoid hemorrhage patients.[SEP]Relations: subarachnoid hemorrhage (disease) has relations: contraindication with Tranexamic acid, contraindication with Tranexamic acid, disease_disease with acquired aneurysmal subarachnoid hemorrhage, disease_disease with acquired aneurysmal subarachnoid hemorrhage, disease_protein with EDNRB, disease_protein with EDNRB, disease_protein with PPARG, disease_protein with PPARG, disease_protein with ADORA1, disease_protein with ADORA1. Definitions: death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. subarachnoid hemorrhage defined as following: Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.. nimodipine defined as following: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.. SAH defined as following: A Turkic language spoken by the Yakut people in the Sakha Republic in the Russian Federation.. vasospasm defined as following: spasm of the blood vessels resulting in decrease in their caliber..", "label": "no"} {"id": "converted_3035", "sentence1": "Is Lasmiditan effective for migraine?", "sentence2": "Amongst the ditans, lasmiditan: (i) fails to constrict human coronary arteries; and (ii) is effective for the acute treatment of migraine in preliminary Phase III clinical trials., Although ongoing phase III clinical trials are needed to confirm its efficacy and safety, lasmiditan might offer an alternative to treat acute migraine with no associated cardiovascular risk., Lasmiditan is considered to be the first member of a new drug category, the neurally acting anti-migraine agent (NAAMA), Lasmiditan for the treatment of acute migraine: a review and potential role in clinical practice., Lasmiditan, a highly selective 5-HT1F agonist, has completed two Phase III randomized, double blind, placebo-controlled clinical trials, with a third - a long-term, open-label safety study - still underway. Research to date suggests lasmiditan lacks vasoconstrictive properties and may be a safe and effective treatment option in patients refractory to current acute migraine medications or who have cardiovascular risk factors., Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study., Compared with placebo, more patients dosed with lasmiditan 200 mg were free of headache pain at 2 hours after dosing (32.2% vs 15.3%; odds ratio [OR] 2.6, 95% confidence interval [CI] 2.0-3.6, p< 0.001), similar to those dosed with lasmiditan 100 mg (28.2%; OR 2.2, 95% CI 1.6-3.0, p< 0.001). Furthermore, compared with those dosed with placebo, more patients dosed with lasmiditan 200 mg (40.7% vs 29.5%; OR 1.6, 95% CI 1.3-2.1, p< 0.001) and lasmiditan 100 mg (40.9%; OR 1.7, 95% CI, 1.3-2.2, p< 0.001) were free of their MBS at 2 hours after dosing., CONCLUSIONS: Lasmiditan dosed at 200 and 100 mg was efficacious and well tolerated in the treatment of acute migraine among patients with a high level of cardiovascular risk factors, CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack., For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT(1F) receptor agonist like lasmiditan is effective in the acute treatment of migraine. , While lasmiditan most likely is effective in the treatment of migraine attacks it had, unfortunately, a high incidence of CNS related AEs in the oral RCT. , Acute treatment of migraine with the selective 5-HT1F receptor agonist lasmiditan--a randomised proof-of-concept trial.At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine. , Lasmiditan for the treatment of acute migraine: a review and potential role in clinical practice. , BACKGROUND\nLasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study., INTERPRETATION\nOral lasmiditan seems to be safe and effective in the acute treatment of migraine., The 5-HT1F receptor agonist lasmiditan, a drug acting through non-vasoconstrictive mechanisms, represents a promising safe, effective and tolerated acute migraine therapy also for patients at cardiovascular risk., For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT(1F) receptor agonist like lasmiditan is effective in the acute treatment of migraine., The 5-HT1F receptor agonist lasmiditan as a potential treatment of migraine attacks: a review of two placebo-controlled phase II trials., Within the past few years, new and promising drugs such as more specific 5-HT 1F receptor agonists (that is, lasmiditan) and monoclonal calcitonin gene-related peptide (CGRP) receptor antibodies entered advanced development phases while non-invasive neuromodulatory approaches were suggested to be potentially effective as non-pharmaceutical interventions for migraine., CLASSIFICATION OF EVIDENCE\nThis study provides Class I evidence that for adult patients with migraine, lasmiditan increases the proportion of subjects who are headache pain free at 2 hours after treating a migraine attack., BACKGROUND Lasmiditan (COL-144) is a novel, centrally acting, highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity that seemed effective when given as an intravenous infusion in a proof-of-concept migraine study., INTERPRETATION Oral lasmiditan seems to be safe and effective in the acute treatment of migraine., Research to date suggests lasmiditan lacks vasoconstrictive properties and may be a safe and effective treatment option in patients refractory to current acute migraine medications or who have cardiovascular risk factors., The non-vascular, neural mechanism of action of lasmiditan may offer an alternative means to treat migraine especially in patients who have contra-indications for agents with vasoconstrictor activity., Compared with placebo, more patients dosed with lasmiditan 200 mg were free of headache pain at 2 hours after dosing (32.2% vs 15.3%; odds ratio [OR] 2.6, 95% confidence interval [CI] 2.0-3.6,Supernumerary mandibular right central primary incisor
. deafness defined as following: A condition in which a person partially loses the ability to hear sounds in one or both ears.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. mutism defined as following: The inability to generate oral-verbal expression, despite normal comprehension of speech. This may be associated with BRAIN DISEASES or MENTAL DISORDERS. Organic mutism may be associated with damage to the FRONTAL LOBE; BRAIN STEM; THALAMUS; and CEREBELLUM. Selective mutism is a psychological condition that usually affects children characterized by continuous refusal to speak in social situations by a child who is able and willing to speak to selected persons. Kussmal aphasia refers to mutism in psychosis. (From Fortschr Neurol Psychiatr 1994; 62(9):337-44). hypothyroidism defined as following: A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction.. cochlea defined as following: The part of the inner ear (LABYRINTH) that is concerned with hearing. It forms the anterior part of the labyrinth, as a snail-like structure that is situated almost horizontally anterior to the VESTIBULAR LABYRINTH.. DFNB4 defined as following: An autosomal recessive condition caused by mutation(s) in one of several genes, most often SLC26A4 encoding pendrin. It is characterized by hearing loss and enlargement of the vestibular aqueduct. Mutation(s) in the SLC26A4 gene also cause Pendred syndrome.. Pendred syndrome defined as following: A condition associated with reduced export of iodide across the apical membrane of the follicular cells of the thyroid gland that may progress to hypothyroidism. Pendred syndrome is associated with an increased risk of goiter and sensorineural hearing loss due to malformations of the inner ear (vestibular system). Inactivating mutations in the SLC26A4 gene encoding the pendrin transport protein are responsible for the condition..", "label": "yes"} {"id": "converted_1612", "sentence1": "Is physical performance influenced by thyroid hormone metabolism?", "sentence2": "Longitudinal analysis showed that in Eut men higher baseline FT4 was significantly (p = 0.02) predictive of a lower SPPB score at the 3-year follow-up, Even a modest thyroid hormone excess is associated with a reduced physical function in elderly men., Oral L-thyroxine treatment was started and at a 1-month follow-up examination, mental status and physical performance were improved, In a population of independently living elderly men, higher FT4 and rT3 concentrations are associated with a lower physical function, She had generalised weakness of muscles, cold intolerance and a reduced physical performance., Replacement therapy by oral administration of L-thyroxin resulted in a gradual improvement of the patient's state, multivariate analysis revealed that total T3 was an independent predictor of VO2max, changes in thyroid hormone were closely correlated to myocardial functional status in patients with heart failure., THR among patients with SCH is beneficial not only by improvement in lipid profile, as well as by improvement in cognitive and functional status,, CONCLUSIONS: Even a modest thyroid hormone excess is associated with a reduced physical function in elderly men., Subclinical hyperthyroidism (SH) may be responsible for many cardiovascular changes, including an impaired exercise performance., BACKGROUND: Physiological changes in thyroid hormone concentrations might be related to changes in the overall physical function in the elderly.[SEP]Relations: response to thyroid hormone has relations: bioprocess_bioprocess with response to hormone, bioprocess_bioprocess with response to hormone, bioprocess_bioprocess with cellular response to thyroid hormone stimulus, bioprocess_bioprocess with cellular response to thyroid hormone stimulus, bioprocess_protein with HPN, bioprocess_protein with HPN, bioprocess_protein with GBA, bioprocess_protein with GBA, bioprocess_bioprocess with response to thyroxine, bioprocess_bioprocess with response to thyroxine. Definitions: L-thyroxin defined as following: The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.. THR defined as following: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.. cardiovascular defined as following: The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body.. heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. thyroid hormone defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs.. SCH defined as following: A hysterectomy that removes the uterus and leaves the cervix in place..", "label": "yes"} {"id": "converted_2149", "sentence1": "Is apremilast effective for psoriasis?", "sentence2": "CONCLUSION: Apremilast reduces the severity of nail/scalp psoriasis., CONCLUSIONS: Apremilast demonstrated clinically meaningful improvements in psoriatic arthritis and psoriasis at week 16; sustained improvements were seen with continued treatment through 52 weeks., Apremilast: A Novel Drug for Treatment of Psoriasis and Psoriatic Arthritis., In those that involved doses of 30 mg twice daily, a significantly greater percentage of patients receiving apremilast (28.8% to 40.9%) compared with placebo (5.3% to 5.8%) achieved at least 75% improvement from baseline in Psoriasis Area and Severity Index score at 16 weeks., CONCLUSIONS: Apremilast has a novel mechanism of action and is safe and effective for the management of psoriasis and psoriatic arthritis. At this time, apremilast should be reserved for patients unable to take disease-modifying antirheumatic drugs., Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis [ESTEEM] 1)., More recently, three larger double-blinded, and randomized multicenter studies demonstrate that apremilast is efficacious in the treatment of psoriasis and PsA, with significantly higher numbers of apremilast-treated patients achieving endpoints of a 75% reduction compared to baseline in Psoriasis Area and Severity Index (PASI-75) or American College of Rheumatology-20 scores, relative to placebo., No new significant adverse events emerged with continued apremilast exposure versus the placebo-controlled period.Data were limited to 52 weeks and may not generalize to nonplaque psoriasis.Apremilast was effective in moderate to severe plaque psoriasis.Respond with exceptions, completions and modifications or revisions done before completion
. polyposis defined as following: A condition characterized by the presence of numerous polyps.. nNO defined as following: One of the two written standards of the Norwegian language.. dupilumab defined as following: A recombinant human monoclonal immunoglobulin G4 (IgG4) antibody directed against the alpha chain of the interleukin-4 receptor (IL-4R alpha) with potential immunomodulatory activities. Upon injection, dupilumab selectively binds to the IL-4R alpha chain. This disrupts IL-4/IL-13 signaling and prevents the activation of downstream pathways that mediate type 2 inflammation and may potentially inhibit tumor cell proliferation, survival, and metastasis. IL-4 and IL-13 receptors are present on the surface of numerous cells involved in the pathophysiology of type-2 helper T-cell (Th2) allergic responses, including B-lymphocytes, eosinophils, dendritic cells (DCs), monocytes, macrophages, basophils, keratinocytes, bronchial epithelial cells, endothelial cells, fibroblasts, and airway smooth muscle cells. Additionally, both IL-4 and IL-13 receptors are overexpressed in a variety of cancers and IL-4 and IL-13 and may serve as biomarkers for cancer aggressiveness. IL-4 and IL-13 are thought to be key regulatory cytokines in the tumor microenvironment (TME) and may play a role in the activation of tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) that mediate tumor cell survival..", "label": "yes"} {"id": "converted_2602", "sentence1": "Is Rucaparib effective for ovarian cancer?", "sentence2": "INTERPRETATION: In patients with BRCA mutant or BRCA wild-type and LOH high platinum-sensitive ovarian carcinomas treated with rucaparib, progression-free survival was longer than in patients with BRCA wild-type LOH low carcinomas., High LOH is associated with response to the PARP inhibitor rucaparib in BRCA wild-type ovarian cancer., Rucaparib Approved for Ovarian Cancer., The FDA approved the PARP inhibitor rucaparib to treat women with advanced ovarian cancer who have already been treated with at least two chemotherapies and have a BRCA1 or BRCA2 gene mutation identified by an approved companion diagnostic test., Rucaparib (Rubraca™) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor being developed by Clovis Oncology, Inc. (Boulder, CO, USA) for the treatment of solid tumours. It has been approved in the USA as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies. , In 2016, the US Food and Drug Administration approved three novel drugs for the treatment of solid malignancies-olaratumab in selected patients with soft-tissue sarcoma, atezolizumab for the treatment of bladder cancer, and rucaparib for the treatment of ovarian cancer; also in 2016, the use of previously approved anticancer agents (including atezolizumab) was expanded into 11 new patient populations. , Conclusions:Rucaparib was tolerable and had activity in patients with platinum-sensitive germlineBRCA1/2-mutated HGOC., OBJECTIVE: To review the pharmacology, safety, efficacy, and the role of rucaparib in the treatment of relapsed, advanced ovarian cancer.Participant material that is brought forth (produced) in the act (e.g., specimen in a specimen collection, access or drainage in a placement service, medication package in a dispense service). It does not matter whether the material produced had existence prior to the service, or whether it is created in the service (e.g., in supply services the product is taken from a stock).
. sequence alignments defined as following: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.. Mercury defined as following: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to MERCURY POISONING. Because of its toxicity, the clinical use of mercury and mercurials is diminishing.. sequence defined as following: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence..", "label": "yes"} {"id": "converted_207", "sentence1": "Does administration of triiodothyronine improve outcome following coronary artery bypass grafting?", "sentence2": "Serum T3 concentrations were significantly higher with fewer patients having T3 concentrations below the normal range in the T3 group than the placebo group throughout the postoperative period. Hemodynamic variables, postoperative inotrope requirement, and outcome variables showed no differences between the groups, We conclude that although widespread interest has been shown on the use of thyroid hormones in the perioperative period, and the effect of cardiopulmonary bypass on thyroid hormone metabolism widely studied, there is no substantial evidence to justify routine use of thyroid hormones in patients undergoing coronary artery bypass grafting., Treatment with GIK, T3, and GIK/T3 improves hemodynamic performance and results in reduced cTnI release in patients undergoing on-pump CABG surgery., Perioperative administration of triiodothyronine increased cardiac output slightly and decreased systemic vascular resistance, but it had no effect on operative outcome., Parenteral triiodothyronine given after crossclamp removal during elective coronary artery bypass grafting significantly improved postoperative ventricular function, reduced the need for treatment with inotropic agents and mechanical devices, and decreased the incidence of myocardial ischemia. The incidence of atrial fibrillation was slightly decreased, and the need for postoperative pacemaker support was reduced., Perioperative T3 administration decreased the incidence and need for treatment of postoperative atrial fibrillation., Intravenous T(3) does not have dramatic effects on hemodynamic variables in this setting as has been previously suggested. , Raising serum triiodothyronine concentrations in patients undergoing coronary-artery bypass surgery increases cardiac output and lowers systemic vascular resistance, but does not change outcome or alter the need for standard postoperative therapy., No significant differences were noted in the pre and post CPB hemodynamics between the two groups for the most part of the study except that heart rate was increased in T3 group., The haemodynamic parameters were no different between the two groups at any postoperative time point. Likewise, density and affinity of lymphocyte beta-adrenoceptors were not significantly different from pre-operative values in either group.[SEP]Relations: Coronary artery atherosclerosis has relations: drug_effect with Rivastigmine, drug_effect with Rivastigmine, drug_effect with Vincristine, drug_effect with Vincristine, drug_effect with Varenicline, drug_effect with Varenicline, drug_effect with Ropinirole, drug_effect with Ropinirole, drug_effect with Fenofibrate, drug_effect with Fenofibrate. Definitions: triiodothyronine defined as following: A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.. cTnI defined as following: Troponin I, cardiac muscle (210 aa, ~24 kDa) is encoded by the human TNNI3 gene. This protein is involved in muscle filament movement in cardiac cells.. atrial fibrillation defined as following: An electrocardiographic finding of a supraventricular arrhythmia characterized by the replacement of consistent P waves by rapid oscillations or fibrillatory waves that vary in size, shape and timing and are accompanied by an irregularly irregular ventricular response. (CDISC). thyroid hormones defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs.. T3 defined as following: This gene plays a regulatory role in the production and utilization of ATP.. myocardial ischemia defined as following: Thickening and loss of elasticity of the CORONARY ARTERIES, leading to progressive arterial insufficiency (CORONARY DISEASE)..", "label": "no"} {"id": "converted_3339", "sentence1": "Can MVA85A confer immunity against smallpox?", "sentence2": "We assessed the safety, immunogenicity, and efficacy of a candidate tuberculosis vaccine, modified vaccinia virus Ankara expressing antigen 85A (MVA85A), in adults infected with HIV-1., Safety, immunogenicity, and efficacy of the candidate tuberculosis vaccine MVA85A in healthy adults infected with HIV-1: a randomised, placebo-controlled, phase 2 trial.[SEP]", "label": "no"} {"id": "converted_309", "sentence1": "Is TREM2 associated with Alzheimer's disease in humans?", "sentence2": "Genetic deficits and loss of function for the triggering receptor expressed in myeloid cells 2 (TREM2; encoded at chr6p21.1), a transmembrane spanning stimulatory receptor of the immunoglobulin/lectin-like gene superfamily, have been associated with deficiencies in phagocytosis and the innate immune system in Alzheimer's disease., Recent works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD),, possible involvement of TREM2 in AD pathogenesis., TREM2 is associated with the risk of Alzheimer's disease in Spanish population., Two recent studies have reported the association of rs75932628-T in the TREM2 gene with the risk for Alzheimer's disease (AD)., we report the first positive replication study in a Spanish population and confirm that TREM2 rs75932628-T is associated with the risk for AD., (TREM2) has recently been identified as a rare risk factor for late-onset Alzheimer's disease (AD)., In this study we examined the association between TREM2 exon 2 variants and early-onset AD in a sample of Caucasian subjects of French origin including 726 patients with age of onset ≤65 years and 783 controls., We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set, The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001)., Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease, Recent works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD), with an odds ratio similar to that of the apolipoprotein E ε4 allele., The rs75932628-T variant of the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has recently been identified as a rare risk factor for late-onset Alzheimer's disease (AD)., BACKGROUND: Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia., CONCLUSIONS: Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease., RESULTS: A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P=3.42×10(-10)).[SEP]Relations: TREM2 has relations: disease_protein with Alzheimer disease, disease_protein with Alzheimer disease, disease_protein with dementia (disease), disease_protein with dementia (disease), disease_protein with semantic dementia, disease_protein with semantic dementia, disease_protein with frontotemporal dementia, disease_protein with frontotemporal dementia, disease_protein with dystonia, disease_protein with dystonia. Definitions: variants defined as following: An alteration or difference from a norm or standard.. TREM2 defined as following: Triggering receptor expressed on myeloid cells 2 (230 aa, ~25 kDa) is encoded by the human TREM2 gene. This protein plays a role in macrophage and dendritic cell immune responses.. gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. myeloid cells 2 defined as following: The classes of BONE MARROW-derived blood cells in the monocytic series (MONOCYTES and their precursors) and granulocytic series (GRANULOCYTES and their precursors).. TREM2 gene defined as following: This gene plays a role in the activation of immune responses.. dementia defined as following: The presence of dementia in an individual younger than age sixty five.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. apolipoprotein E defined as following: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.. humans defined as following: Members of the species Homo sapiens..", "label": "yes"} {"id": "converted_3130", "sentence1": "Are apoE mimetics being considered as a treatment against Alzheimer's disease?", "sentence2": "The apolipoprotein-E-mimetic COG112 protects amyloid precursor protein intracellular domain-overexpressing animals from Alzheimer's disease-like pathological features., Studies show that administration of apolipoprotein E (apoE) and apoE-derived small peptide mimetics protect AD mouse models against these AD-like features.[SEP]Relations: amyloid precursor protein metabolic process has relations: bioprocess_protein with APOE, bioprocess_protein with APOE, bioprocess_protein with APH1A, bioprocess_protein with APH1A, bioprocess_protein with PSENEN, bioprocess_protein with PSENEN, bioprocess_bioprocess with amyloid precursor protein catabolic process, bioprocess_bioprocess with amyloid precursor protein catabolic process. apolipoprotein E recycling has relations: bioprocess_bioprocess with protein transport, bioprocess_bioprocess with protein transport. Definitions: peptide defined as following: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.. apoE defined as following: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.. amyloid precursor protein defined as following: A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65..", "label": "yes"} {"id": "converted_4377", "sentence1": "Can bergapten cause phototoxicity?", "sentence2": "Furthermore, the phototoxicity of bergapten combined with ultraviolet light has always been mentioned., The phototoxicity of bergapten as a side effect should be further avoided. [SEP]Definitions: bergapten defined as following: A linear furanocoumarin that has phototoxic and anti-inflammatory properties, with effects similar to METHOXSALEN. It is used in PUVA THERAPY for the treatment of PSORIASIS..", "label": "yes"} {"id": "converted_2078", "sentence1": "Is the number of described human nuclear mutations less than 50000?", "sentence2": "The number of known mutations in human nuclear genes, underlying or associated with human inherited disease, has now exceeded 100,000 in more than 3700 different genes (Human Gene Mutation Database)., The Human Gene Mutation Database (HGMD®) is a comprehensive collection of germline mutations in nuclear genes that underlie, or are associated with, human inherited disease. By June 2013, the database contained over 141,000 different lesions detected in over 5,700 different genes, with new mutation entries currently accumulating at a rate exceeding 10,000 per annum., By March 2012, the database contained in excess of 123,600 different lesions (HGMD Professional release 2012.1) detected in 4,514 different nuclear genes, with new entries[SEP]Relations: Lacrimation abnormality has relations: disease_phenotype_positive with Coffin-Siris syndrome, disease_phenotype_positive with Coffin-Siris syndrome, disease_phenotype_positive with Stüve-Wiedemann syndrome, disease_phenotype_positive with Stüve-Wiedemann syndrome, disease_phenotype_positive with Johanson-Blizzard syndrome, disease_phenotype_positive with Johanson-Blizzard syndrome, disease_phenotype_positive with Williams syndrome, disease_phenotype_positive with Williams syndrome, disease_phenotype_positive with limbal stem cell deficiency, disease_phenotype_positive with limbal stem cell deficiency. Definitions: lesions defined as following: A localized pathological or traumatic structural change, damage, deformity, or discontinuity of tissue, organ, or body part.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. human defined as following: Members of the species Homo sapiens..", "label": "no"} {"id": "converted_1370", "sentence1": "Are nucleosomes positioned at DNA replication origins?", "sentence2": "yeast origins are characterized by an asymmetric pattern of positioned nucleosomes flanking the ACS. The origin sequences are sufficient to maintain a nucleosome-free origin; however, ORC is required for the precise positioning of nucleosomes flanking the origin., Here, we identify nucleosome occupancy as a likely candidate to set up ORI distribution, we demonstrate that open chromatin domains, characterized by nucleosome depletion, are preferentially permissive for replication, Nucleosome assembly of the template prevented DNA replication. Replication of chromosomes was severely inhibited at more than two-thirds of physiological nucleosome density[SEP]Relations: nucleosome assembly has relations: bioprocess_bioprocess with DNA replication-dependent nucleosome assembly, bioprocess_bioprocess with DNA replication-dependent nucleosome assembly, bioprocess_protein with SET, bioprocess_protein with SET, bioprocess_bioprocess with DNA replication-independent nucleosome assembly, bioprocess_bioprocess with DNA replication-independent nucleosome assembly, bioprocess_protein with SETSIP, bioprocess_protein with SETSIP, bioprocess_protein with NPM1, bioprocess_protein with NPM1. Definitions: ORC defined as following: A multisubunit complex that is located at the replication origins of a chromosome. [GOC:elh]. ORI defined as following: An Indo-Aryan language that is spoken mostly in eastern India.. chromosomes defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.. nucleosomes defined as following: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4.. Nucleosome assembly defined as following: The aggregation, arrangement and bonding together of a nucleosome, the beadlike structural units of eukaryotic chromatin composed of histones and DNA. [GOC:mah].", "label": "no"} {"id": "converted_3488", "sentence1": "Does metformin has as an antitumor effect?", "sentence2": " an association between metformin and tumorigenesis, Metformin, an antidiabetic drug, inhibits the endometrial cancer cell growth in vivo by improving the insulin resistance;, There is no evidence of antitumor effect of metformin. A possible decrease only for breast, liver and prostate cancer, is compatible with random fluctuations., The anti-tumor effect of metformin is widely known, however, there is only limited evidence regarding the anti-angiogenesis effect and chemosensitization of metformin and its underlying mechanisms in PDAC[SEP]Relations: Metformin has relations: drug_effect with Lethargy, drug_effect with Lethargy, drug_effect with Nausea, drug_effect with Nausea, drug_effect with Vertigo, drug_effect with Vertigo, drug_effect with Headache, drug_effect with Headache, drug_effect with Hypothermia, drug_effect with Hypothermia. Definitions: metformin defined as following: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289). endometrial cancer defined as following: Primary or metastatic malignant neoplasm involving the endometrium (mucous membrane that lines the endometrial cavity).. breast defined as following: In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.. prostate cancer defined as following: A primary or metastatic malignant tumor involving the prostate gland. The vast majority are carcinomas.. antidiabetic drug defined as following: Any substance used to reduce hyperglycemia or treat disorders associated with diabetes. Based on their mechanism of action, this class of agents can be classified to the following groups: directly acting insulomimetics, which activates insulin receptors; indirectly acting insulinomimetics, which increase insulin release such as sulfonylureas or which potentiate the effect of insulin such as metformin; those act directly on the metabolism of glucose such as inhibitors of glucosidases and inhibitors of aldose reductase.. PDAC defined as following: A rare clinical entity including as main characteristics anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia. Only five cases have been reported so far, two of who were siblings. In the three nonfamilial cases, unilateral pulmonary agenesis and microphthalmia were associated with diaphragmatic hernia and pulmonary vessel agenesis. It has been suggested that two different entities can be distinguished: on one hand, the association of anophthalmia-pulmonary hypoplasia with/without anomalies of the face, heart, spleen and uterus, which may be due to a putative autosomal recessive gene with pleiotropic effects; on the other hand, a sporadic association including pulmonary hypoplasia, anophthalmia, unilateral diaphragmatic defect and agenesis of the pulmonary trunk, which may represent the expression of a developmental field defect. There is evidence that syndromic microphthalmia- is caused by homozygous or compound heterozygous mutation in the STRA6 gene on chromosome 15q24..", "label": "yes"} {"id": "converted_3804", "sentence1": "Have the rotavirus vaccines changed the predominant rotavirus genotypes?", "sentence2": "This study describes the distribution and diversity of rotavirus genotypes before and after rotavirus vaccine introduction into the Australian NIP., G1P[8] was the dominant genotype nationally in the prevaccine era (1995-2006). Following vaccine introduction (2007-2015), greater genotype diversity was observed with fluctuating genotype dominance. Genotype distribution varied based on the vaccine implemented, with G12P[8] dominant in states using RotaTeq, and equine-like G3P[8] and G2P[4] dominant in states and territories using Rotarix., The increased diversity and differences in genotype dominance observed in states using RotaTeq (G12P[8]), and in states and territories using Rotarix (equine-like G3P[8] and G2P[4]), suggest that these vaccines exert different immunological pressures that influence the diversity of rotavirus strains circulating in Australia.[SEP]Relations: Rotavirus vaccine has relations: drug_drug with Flunisolide, drug_drug with Flunisolide, drug_drug with Hypericin, drug_drug with Hypericin, drug_drug with Flucytosine, drug_drug with Flucytosine, drug_drug with Fluocortin, drug_drug with Fluocortin, drug_drug with Corticotropin, drug_drug with Corticotropin. Definitions: rotavirus defined as following:rotavirus vaccine, tetravalent, live, oral
. genotype defined as following: The determination of the DNA sequence of an individual.. vaccines defined as following: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases..", "label": "yes"} {"id": "converted_3211", "sentence1": "Can antisense threapy be used for Huntington's disease?", "sentence2": "In this issue of Neuron, Kordasiewicz et al. (2012) show the benefit of transient antisense oligonucleotide (ASO) therapy to degrade Huntingtin mRNA and elicit sustained therapeutic benefit in HD mice., \"Huntingtin holiday\": progress toward an antisense therapy for Huntington's disease.[SEP]Relations: Huntington disease has relations: disease_disease with neurodegenerative disease with chorea, disease_disease with neurodegenerative disease with chorea, disease_disease with Huntington disease and related disorders, disease_disease with Huntington disease and related disorders, disease_disease with juvenile Huntington disease, disease_disease with juvenile Huntington disease, disease_protein with GAL, disease_protein with GAL, disease_protein with FAAH, disease_protein with FAAH. Definitions: Huntingtin defined as following: Huntingtin (3144 aa, ~348 kDa) is encoded by the human HTT gene. This protein may be involved in the regulation of vesicular transport.. Huntington's disease defined as following: A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4). Neuron defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. HD defined as following: A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen..", "label": "yes"} {"id": "converted_732", "sentence1": "Is autism one of the characteristics of Moebius syndrome?", "sentence2": "The diagnosis of Moebius syndrome, a rare congenital disorder, is primarily based on congenital facial and abducent nerve palsy. Involvement of other cranial nerves is also common. Occasionally the V, X, XI, and XII cranial nerves are involved, resulting in a difficulty to chew, swallow, and cough, which often leads to respiratory complications. Mental retardation and autism have been reported in some cases, Moebius sequence is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. A strong association of Moebius sequence with autism spectrum disorders (ASDs) has been suggested in earlier studies with heterogenous age groups, Certain genetic syndromes are providing us with extremely valuable information about the role played by genetics in autism. This is the case of the following syndromes: Angelman syndrome, Prader-Willi syndrome, 15q11-q13 duplication, fragile X syndrome, fragile X premutation, deletion of chromosome 2q, XYY syndrome, Smith-Lemli-Opitz syndrome, Apert syndrome, mutations in the ARX gene, De Lange syndrome, Smith-Magenis syndrome, Williams syndrome, Rett syndrome, Noonan syndrome, Down syndrome, velo-cardio-facial syndrome, myotonic dystrophy, Steinert disease, tuberous sclerosis, Duchenne's disease, Timothy syndrome, 10p terminal deletion, Cowden syndrome, 45,X/46,XY mosaicism, Myhre syndrome, Sotos syndrome, Cohen syndrome, Goldenhar syndrome, Joubert syndrome, Lujan-Fryns syndrome, Moebius syndrome, hypomelanosis of Ito, neurofibromatosis type 1, CHARGE syndrome and HEADD syndrome., Seventeen children and young adults with Moebius syndrome were examined with a view to finding symptoms of autism. Some 40% of the group showed all or many of the symptoms typical of autistic disorder, Fifty-nine cases with infantile autism/autistic disorder were subclassified according to associated medical condition (fragile-X, tuberous sclerosis, neurofibromatosis, hypo-melanosis of Ito, Moebius syndrome, Rett syndrome, and a 'new' syndrome associated with a marker chromosome)., Autism spectrum disorders in children and adolescents with Moebius sequence., Moebius sequence and autism spectrum disorders--less frequently associated than formerly thought., A strong association of Moebius sequence with autism spectrum disorders (ASDs) has been suggested in earlier studies with heterogenous age groups., Autistic behaviour in Moebius syndrome., The high frequency of autistic symptoms in Moebius syndrome might be a marked overrepresentation and could be suggestive of a common underlying neurobiological deficit at the brainstem level., Autism spectrum disorders in children and adolescents with Moebius sequence., Moebius sequence and autism spectrum disorders--less frequently associated than formerly thought., Autistic behaviour in Moebius syndrome.[SEP]Relations: Mobius syndrome has relations: disease_disease with Moebius axonal neuropathy hypogonadism, disease_disease with Moebius axonal neuropathy hypogonadism. autism spectrum disorder has relations: disease_protein with MBD4, disease_protein with MBD4, disease_disease with Asperger syndrome, disease_disease with Asperger syndrome, disease_protein with ADA, disease_protein with ADA, disease_protein with MBD3, disease_protein with MBD3. Definitions: Smith-Magenis syndrome defined as following: A genetic syndrome caused by an interstitial deletion in chromosome 17p11.2. It is characterized by mild to moderate mental retardation, distinctive facial features (flat head, square face, and deep set-eyes), sleep disturbances, attention deficit disorders, and temper tantrums.. autism defined as following: A disorder beginning in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual. (DSM-V). Smith-Lemli-Opitz syndrome defined as following: An autosomal recessive disorder of CHOLESTEROL metabolism. It is caused by a deficiency of 7-dehydrocholesterol reductase, the enzyme that converts 7-dehydrocholesterol to cholesterol, leading to an abnormally low plasma cholesterol. This syndrome is characterized by multiple CONGENITAL ABNORMALITIES, growth deficiency, and INTELLECTUAL DISABILITY.. De Lange syndrome defined as following: An X-linked inherited form of Cornelia De Lange syndrome caused by mutations in the SMC1A gene mapped to chromosome Xp11.22. Patients have a milder form of the syndrome compared to patients with the NIPBL gene mutation.. autism spectrum disorders defined as following: A spectrum of developmental disorders that includes autism, Asperger syndrome, and Rett syndrome. Signs and symptoms include poor communication skills, defective social interactions, and repetitive behaviors.. Mental retardation defined as following: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28). Noonan syndrome defined as following: Noonan syndrome caused by autosomal dominant mutation(s) in the KRAS gene, encoding GTPase KRas.. cranial nerves defined as following: Twelve pairs of nerves that carry general afferent, visceral afferent, special afferent, somatic efferent, and autonomic efferent fibers.. Steinert disease defined as following: A rare autosomal dominant disorder caused by mutations in the DMPK gene. It is characterized by myotonia, muscular dystrophy, hypogonadism, heart conduction defects and cataracts.. Duchenne's disease defined as following: Parenchymatous NEUROSYPHILIS marked by slowly progressive degeneration of the posterior columns, posterior roots, and ganglia of the spinal cord. The condition tends to present 15 to 20 years after the initial infection and is characterized by lightening-like pains in the lower extremities, URINARY INCONTINENCE; ATAXIA; severely impaired position and vibratory sense, abnormal gait (see GAIT DISORDERS, NEUROLOGIC), OPTIC ATROPHY; Argyll-Robertson pupils, hypotonia, hyperreflexia, and trophic joint degeneration (Charcot's Joint; see ARTHROPATHY, NEUROGENIC). (From Adams et al., Principles of Neurology, 6th ed, p726). Lujan-Fryns syndrome defined as following: A syndrome marked by marfanoid habitus (tall stature with long and slim limbs, little subcutaneous fat, arachnodactyly, joint hyperextensibility, narrow face, small chin, large testes, and hypotonia) associated with mental retardation.. hypomelanosis defined as following: A condition caused by a deficiency or a loss of melanin pigmentation in the epidermis, also known as hypomelanosis. Hypopigmentation can be localized or generalized, and may result from genetic defects, trauma, inflammation, or infections.. velo-cardio-facial syndrome defined as following: Typical facies with a prominent nose and retruded mandible, cleft palate, cardiovascular defects, learning disability, retarded mental development, and short stature. Elements of this syndrome are frequently present in the Robin syndrome.. Goldenhar syndrome defined as following: Mandibulofacial dysostosis with congenital eyelid dermoids.. tuberous sclerosis defined as following: Tuberous sclerosis mapped to chromosome 16p13.3 (TSC2 gene).. Angelman syndrome defined as following: A syndrome characterized by multiple abnormalities, MENTAL RETARDATION, and movement disorders. Present usually are skull and other abnormalities, frequent infantile spasms (SPASMS, INFANTILE); easily provoked and prolonged paroxysms of laughter (hence \"happy\"); jerky puppetlike movements (hence \"puppet\"); continuous tongue protrusion; motor retardation; ATAXIA; MUSCLE HYPOTONIA; and a peculiar facies. It is associated with maternal deletions of chromosome 15q11-13 and other genetic abnormalities. (From Am J Med Genet 1998 Dec 4;80(4):385-90; Hum Mol Genet 1999 Jan;8(1):129-35). neurofibromatosis defined as following: An autosomal dominant disorder characterized by a high incidence of bilateral acoustic neuromas as well as schwannomas (NEURILEMMOMA) of other cranial and peripheral nerves, and other benign intracranial tumors including meningiomas, ependymomas, spinal neurofibromas, and gliomas. The disease has been linked to mutations of the NF2 gene (GENES, NEUROFIBROMATOSIS 2) on chromosome 22 (22q12) and usually presents clinically in the first or second decade of life.. Down syndrome defined as following: A chromosome disorder associated either with an extra CHROMOSOME 21 or an effective TRISOMY for chromosome 21. Clinical manifestations include HYPOTONIA, short stature, BRACHYCEPHALY, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, single transverse palmar crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213). XYY syndrome defined as following: A condition caused by the presence of an extra Y chromosome resulting in 47,XYY karyotype in an individual with male phenotype. The condition is characterized by tall stature, increased risk of learning disabilities, and delayed development of speech and language. Testicular function and size are normal.. CHARGE syndrome defined as following: A rare autosomal dominant syndrome usually caused by mutations in the CHD7 gene. The term CHARGE is an acronym for the following unusual congenital abnormalities that are associated with this syndrome: coloboma of the eye, heart defects, choanal atresia, growth and developmental retardation, genital, and ear abnormalities.. Joubert syndrome defined as following: A rare genetic syndrome characterized by the hypoplasia or absence of the cerebellar vermis. Signs and symptoms include rapid breathing (hyperpnea), sleep apnea, abnormal eye movements, mental retardation, and ataxia.. Williams syndrome defined as following: A disorder caused by hemizygous microdeletion of about 28 genes on chromosome 7q11.23, including the ELASTIN gene. Clinical manifestations include SUPRAVALVULAR AORTIC STENOSIS; MENTAL RETARDATION; elfin facies; impaired visuospatial constructive abilities; and transient HYPERCALCEMIA in infancy. The condition affects both sexes, with onset at birth or in early infancy.. Rett syndrome defined as following: An inherited neurological developmental disorder that is associated with X-LINKED INHERITANCE and may be lethal in utero to hemizygous males. The affected female is normal until the age of 6-25 months when progressive loss of voluntary control of hand movements and communication skills; ATAXIA; SEIZURES; autistic behavior; intermittent HYPERVENTILATION; and HYPERAMMONEMIA appear. (From Menkes, Textbook of Child Neurology, 5th ed, p199). Apert syndrome defined as following: An autosomal dominant inherited type of acrocephalosyndactyly caused by mutations in the FGFR2 gene. It is characterized by early closure of the sutures between the skull bones, bulging eyes, low-set ears, fusion of the second, third, and forth fingers, and fusion of the toes.. ARX gene defined as following: This gene plays a role in transcriptional regulation and the development of the brain.. congenital disorder defined as following: existing at, and usually before, birth; referring to conditions that are present at birth, regardless of their causation; inborn metabolism disorders are generally not treed here.. Prader-Willi syndrome defined as following: An autosomal dominant disorder caused by deletion of the proximal long arm of the paternal chromosome 15 (15q11-q13) or by inheritance of both of the pair of chromosomes 15 from the mother (UNIPARENTAL DISOMY) which are imprinted (GENETIC IMPRINTING) and hence silenced. Clinical manifestations include MENTAL RETARDATION; MUSCULAR HYPOTONIA; HYPERPHAGIA; OBESITY; short stature; HYPOGONADISM; STRABISMUS; and HYPERSOMNOLENCE. (Menkes, Textbook of Child Neurology, 5th ed, p229). fragile X syndrome defined as following: A condition characterized genotypically by mutation of the distal end of the long arm of the X chromosome (at gene loci FRAXA or FRAXE) and phenotypically by cognitive impairment, hyperactivity, SEIZURES, language delay, and enlargement of the ears, head, and testes. INTELLECTUAL DISABILITY occurs in nearly all males and roughly 50% of females with the full mutation of FRAXA. (From Menkes, Textbook of Child Neurology, 5th ed, p226). Moebius syndrome defined as following: A syndrome of congenital facial paralysis, frequently associated with abducens palsy and other congenital abnormalities including lingual palsy, clubfeet, brachial disorders, cognitive deficits, and pectoral muscle defects. Pathologic findings are variable and include brain stem nuclear aplasia, facial nerve aplasia, and facial muscle aplasia, consistent with a multifactorial etiology. (Adams et al., Principles of Neurology, 6th ed, p1020). mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"} {"id": "converted_1901", "sentence1": "Is there any role for Pds5b in cohesion establishment?", "sentence2": "Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres., Here, we demonstrate that Pds5 proteins are essential for cohesion establishment by allowing Smc3 acetylation by the cohesin acetyl transferases (CoATs) Esco1/2 and binding of Sororin. While both proteins contribute to telomere and arm cohesion, Pds5B is specifically required for centromeric cohesion. Furthermore, reduced accumulation of Aurora B at the inner centromere region in cells lacking Pds5B impairs its error correction function, promoting chromosome mis-segregation and aneuploidy. Our work supports a model in which the composition and function of cohesin complexes differs between different chromosomal regions., Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres., Here, we demonstrate that Pds5 proteins are essential for cohesion establishment by allowing Smc3 acetylation by the cohesin acetyl transferases (CoATs) Esco1/2 and binding of Sororin.[SEP]Relations: Protein S human has relations: drug_drug with Coagulation Factor IX (Recombinant), drug_drug with Coagulation Factor IX (Recombinant), drug_drug with Platelet Activating Factor, drug_drug with Platelet Activating Factor, drug_drug with p-Coumaric acid, drug_drug with p-Coumaric acid, drug_drug with Peginterferon alfa-2b, drug_drug with Peginterferon alfa-2b. centromere clustering has relations: bioprocess_bioprocess with chromosome localization, bioprocess_bioprocess with chromosome localization. Definitions: proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. centromeres defined as following: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.. Pds5B defined as following: This gene is involved in cell cycle regulation.. Smc3 defined as following: Human SMC3 wild-type allele is located in the vicinity of 10q25 and is approximately 37 kb in length. This allele, which encodes structural maintenance of chromosomes protein 3, is involved in the regulation of chromosome migration during mitosis.. Aurora B defined as following: Aurora kinase B (344 aa, ~39 kDa) is encoded by the human AURKB gene. This protein plays a role in both the modulation of microtubule structure and facilitation of chromosome segregation during mitosis and meiosis.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. telomere defined as following: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.. Pds5b defined as following: This gene is involved in cell cycle regulation..", "label": "yes"} {"id": "converted_3681", "sentence1": "Is Aptiganel effective for treatment of stroke?", "sentence2": "Trends for increased mortality with three NMDA antagonists were seen - selfotel (OR 1.19 [0.81-1.74]), aptiganel (OR 1.32 [0.91-1.93]) and gavestinel (OR 1.12 [0.95-1.32]) - but this did not achieve significance for the NMDA antagonists considered as a class (1.09 [0.96-1.23]). Aptiganel was also associated with a trend towards worse functional outcome (OR 1.20 [0.88-1.65]) although this was not the case for either of the other two compounds., No improvement in clinical outcome of stroke has been seen with competitive NMDA antagonists (selfotel) and non-competitive NMDA antagonists (dextrorphan, GV150526, aptiganel and eliprodil)., Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists (competitive receptor antagonists, ion channel blockers, and glycine antagonists)--such as selfotel, aptiganel, eliprodil, licostinel and gavestinel--failed to show efficacy in clinical trials of stroke or traumatic brain injury. , There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31). At 7 days, placebo-treated patients exhibited slightly greater neurological improvement on the NIH Stroke Scale than high-dose aptiganel patients (mean improvement for placebo group, -0.8 points vs for high-dose aptiganel, 0.9 points; P =.04). The mortality rate at 120 days in patients treated with high-dose aptiganel was higher than that in patients who received placebo (26.3% vs 19.2%; P =.06)., CONCLUSIONS: Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful. The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients., CONCLUSIONS\n\nAptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful., The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients., There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31)., Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists (competitive receptor antagonists, ion channel blockers, and glycine antagonists)--such as selfotel, aptiganel, eliprodil, licostinel and gavestinel--failed to show efficacy in clinical trials of stroke or traumatic brain injury., CONCLUSIONS Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful., Glutamate N-methyl-D-aspartate ( NMDA ) receptor antagonists ( competitive receptor antagonists , ion channel blockers , and glycine antagonists)--such as selfotel , aptiganel , eliprodil , licostinel and gavestinel--failed to show efficacy in clinical trials of stroke or traumatic brain injury, No improvement in clinical outcome of stroke has been seen with competitive NMDA antagonists ( selfotel ) and non-competitive NMDA antagonists ( dextrorphan , GV150526 , aptiganel and eliprodil, There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31)., CONCLUSIONS: Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful., The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients., There was no improvement in outcome for either aptiganel (low-dose or high-dose) group compared with the placebo group at 90 days (median Modified Rankin Scale score for all 3 treatment groups = 3; P =.31)., Aptiganel was not efficacious in patients with acute ischemic stroke at either of the tested doses, and m ay be harmful., The larger proportion of patients with favorable outcomes and lower mortality rate in the placebo group suggest that glutamate blockade with aptiganel may have detrimental effects in an undifferentiated population of stroke patients.[SEP]Relations: Ischemic stroke has relations: drug_effect with Paclitaxel, drug_effect with Paclitaxel, drug_effect with Ramipril, drug_effect with Ramipril, drug_effect with Aripiprazole, drug_effect with Aripiprazole, drug_effect with Sitaxentan, drug_effect with Sitaxentan, drug_effect with Pazopanib, drug_effect with Pazopanib. Definitions: NMDA defined as following: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).. traumatic brain injury defined as following: A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.. low-dose defined as following: A reduced quantity of a therapeutic agent prescribed to be taken at one time or at stated intervals.. dextrorphan defined as following: Dextro form of levorphanol. It acts as a noncompetitive NMDA receptor antagonist, among other effects, and has been proposed as a neuroprotective agent. It is also a metabolite of DEXTROMETHORPHAN.. stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810).", "label": "no"} {"id": "converted_44", "sentence1": "Does BNP increase after intensive exercise in athletes?", "sentence2": "NT-pro-BNP was significantly elevated postexercise in both adults and adolescents and remained above baseline at 24 h in both groups., NT-pro-BNP concentrations increased significantly (28 +/- 17.1 vs 795 +/- 823 ng x L, P < 0.05), whereas postrace cTnT were elevated in just five athletes (20%)., [NT-pro-BNP] was observed immediately after the marathon (median [NT-pro-BNP] before: 39.6 pg ml(-1), after: 138.6 pg ml(-1), p=0.003) with a further increase on day one. [BNP] did not increase immediately after the marathon but increased on day one (median [BNP] before: 15 pg ml(-1), day one: 27.35 pg ml(-1), p=0.006)., Pro-BNP was significantly increased immediately post-race (27+/-21 vs 7+/-2 pmol/L pre-race, P < or = 0.007), which 12-24 h later, decreased to 19+/-14 pmol/L (P = 0.07 vs pre-race)., The relatively high NT-proBNP levels after active recovery when psychophysical stress is higher, because of cycling and cold water immersion, suggest that not only endurance exercise, but also strenuous, stressful short exercise can induce an increase in NT-proBNP concentrations., Running a marathon significantly increases NT-pro-BNP levels in healthy adults. This increase could be partially attributed to cardiac stress., Increases in NT-proBNP can be found in a major part of obviously healthy athletes after prolonged strenuous exercise. The release of BNP during and after exercise may not result from myocardial damage but may have cytoprotective and growth-regulating effects. The different nature of exercise-induced increases in BNP and cardiac troponins has to be elucidated in the future., In healthy cyclists, transient increases in NT-pro-BNP and cTnT are more likely to reflect cardiac fatigue than injury., The rise in BNP in older athletes may reflect a reversible, mainly diastolic left ventricular dysfunction. , Plasma BNP concentrations were higher in both the judo and marathon groups than in controls, and positively correlated with LV mass as well as with deceleration time., Such exercise significantly increased ANP and BNP levels in healthy men, and the increases could be partially attributed to myocardial damage during the race.[SEP]Relations: Nesiritide has relations: drug_effect with Ventricular extrasystoles, drug_effect with Ventricular extrasystoles, contraindication with hypertrophic cardiomyopathy, contraindication with hypertrophic cardiomyopathy, drug_effect with Renal insufficiency, drug_effect with Renal insufficiency, drug_effect with Ventricular arrhythmia, drug_effect with Ventricular arrhythmia. Abnormal A-type atrial natriuretic peptide level has relations: phenotype_phenotype with Increased circulating A-type natriuretic peptide level, phenotype_phenotype with Increased circulating A-type natriuretic peptide level. Definitions: cTnT defined as following: Troponin T, cardiac muscle (298 aa, ~36 kDa) is encoded by the human TNNT2 gene. This protein plays a role in cardiac muscle contraction.. NT-pro-BNP defined as following: N-terminal fragment brain natriuretic protein (76 aa, ~9 kDa) is encoded by the human NPPB gene. This protein is a marker for cardiac failure.. BNP defined as following: A recombinant version of the cardiac neurohormone, human B-type natriuretic peptide (hBNP) produced by the ventricular myocardium. Nesiritide binds to natriuretic peptide receptors on vascular smooth muscle and endothelial cells, through which it triggers guanylate cyclase dependent signal transduction resulting in increase of intracellular concentrations of cGMP. This leads to smooth muscle cell relaxation causing arterial and venous dilatation.. ANP defined as following: A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight PEPTIDES derived from a common precursor and secreted mainly by the HEART ATRIUM. All these peptides share a sequence of about 20 AMINO ACIDS..", "label": "yes"} {"id": "converted_2244", "sentence1": "Does RNA polymerase II have RNA cleavage activity?", "sentence2": "In addition to RNA synthesis, multisubunit RNA polymerases (msRNAPs) support enzymatic reactions such as intrinsic transcript cleavage., msRNAP active sites from different species appear to exhibit differential intrinsic transcript cleavage efficiency and have likely evolved to allow fine-tuning of the transcription process., Here we show that a single amino-acid substitution in the trigger loop (TL) of Saccharomyces RNAP II, Rpb1 H1085Y, engenders a gain of intrinsic cleavage activity where the substituted tyrosine appears to participate in acid-base chemistry at alkaline pH for both intrinsic cleavage and nucleotidyl transfer. , The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex., The transcription factor TFIIS zinc ribbon dipeptide Asp-Glu is critical for stimulation of elongation and RNA cleavage by RNA polymerase II, By site-directed mutagenesis, we have demonstrated that invariant residues Asp-261 and Glu-262 of the nucleic acid-binding TFIIS Zn ribbon are critical for stimulation of both elongation and RNA cleavage activities of RNA polymerase II., Complexes of yeast RNA polymerase II and RNA are substrates for TFIIS-induced RNA cleavage., RNA in such RNA-RNA polymerase complexes undergoes reactions previously thought to be unique to nascent RNA in ternary complexes with DNA, including TFIIS-dependent cleavage and elongation by 3'-terminal addition of NMP from NTP., Nascent RNA cleavage by arrested RNA polymerase II does not require upstream translocation of the elongation complex on DNA., Here we show that in the presence of SII and nucleotides, transcript cleavage is detected during SII-dependent elongation but not during SII-independent transcription. , under typical transcription conditions, SII is necessary but insufficient to activate RNA cleavage. RNA cleavage could serve to move RNA polymerase II away from the transcriptional impediment and/or permit RNA polymerase II multiple attempts at RNA elongation., SII is an RNA polymerase II-binding protein that stimulates transcription elongation and also activates nascent transcript cleavage by RNA polymerase II in elongation complexes in vitro, The RNA polymerase II elongation complex. Factor-dependent transcription elongation involves nascent RNA cleavage., Cleavage was not restricted to an elongation complex arrested at this particular site, showing that nascent RNA hydrolysis is a general property of RNA polymerase II elongation complexes., Elongation factor SII (also known as TFIIS) is an RNA polymerase II binding protein that allows bypass of template arrest sites by activating a nascent RNA cleavage reaction., During gene transcription, the RNA polymerase (Pol) active center can catalyze RNA cleavage., During gene transcription, the RNA polymerase (Pol) active center can catalyze RNA cleavage., The eukaryotic transcription factor TFIIS enhances elongation and nascent transcript cleavage activities of RNA polymerase II in a stalled elongation complex., Rpb9, a small subunit of RNA polymerase II, enhances the cleavage stimulation activity of S-II., These results suggest that both S-II and Rpb9 maintain transcriptional fidelity by stimulating the cleavage activity intrinsic to RNA polymerase II., It is also possible that the transcript cleavage activity of RNA polymerase II represents a proofreading function of the enzyme.., Nascent RNA cleavage by arrested RNA polymerase II does not require upstream translocation of the elongation complex on DNA., Intrinsic transcript cleavage in yeast RNA polymerase II elongation complexes.[SEP]Relations: RNA polymerase binding has relations: molfunc_protein with CCNT2, molfunc_protein with CCNT2, molfunc_protein with YTHDC2, molfunc_protein with YTHDC2, molfunc_protein with PKN2, molfunc_protein with PKN2, molfunc_protein with PPIB, molfunc_protein with PPIB. RNA polymerase III assembly has relations: bioprocess_bioprocess with cellular protein-containing complex assembly, bioprocess_bioprocess with cellular protein-containing complex assembly. Definitions: RNA defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). RNA polymerase II defined as following: A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC 2.7.7.6.. multisubunit RNA polymerases defined as following: Any complex that possesses RNA polymerase activity; generally comprises a catalytic subunit and one or more additional subunits. [GOC:mah]. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. nucleotides defined as following: The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed). TFIIS defined as following: Human TCEA1 wild-type allele is located in the vicinity of 8q11.2 and is approximately 56 kb in length. This allele, which encodes transcription elongation factor A protein 1, plays a role in transcriptional elongation. A chromosomal insertion ins(8)(q12;q11q11) of this gene and the PLAG1 gene may be associated with salivary gland pleomorphic adenoma.. RNA polymerase defined as following: Enzymes that catalyze DNA template-directed extension of the 3'-end of an RNA strand one nucleotide at a time. They can initiate a chain de novo. In eukaryotes, three forms of the enzyme have been distinguished on the basis of sensitivity to alpha-amanitin, and the type of RNA synthesized. (From Enzyme Nomenclature, 1992).. transcript defined as following: The initial RNA molecule produced by transcription..", "label": "yes"} {"id": "converted_3052", "sentence1": "Is Netrin-1 a secreted protein?", "sentence2": "The axon guidance cues netrin-1 is a secreted protein overexpressed in many different cancer tissues, Netrin-1 is a secreted protein that directs long-range axon guidance during early stages of neural circuit formation and continues to be expressed in the mammalian forebrain during the postnatal period of peak synapse formation. , Netrin-1, a laminin-related secreted protein, displays proto-oncogenic activity in cancers., Netrin-1, a multifunctional secreted protein, is up-regulated in cancer and inflammation., etrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker of injury., Netrins are a family of secreted protein related to laminin and act as tropic cues directing axon growth and cell migration during neural development. [SEP]Relations: NTN1 has relations: pathway_protein with Netrin-1 signaling, pathway_protein with Netrin-1 signaling, pathway_protein with Netrin mediated repulsion signals, pathway_protein with Netrin mediated repulsion signals, pathway_protein with Role of second messengers in netrin-1 signaling, pathway_protein with Role of second messengers in netrin-1 signaling, protein_protein with NEO1, protein_protein with NEO1, bioprocess_protein with negative regulation of netrin-activated signaling pathway, bioprocess_protein with negative regulation of netrin-activated signaling pathway. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. laminin defined as following: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. Netrins defined as following: A family of extracellular proteins that are related structurally to LAMININ. They function as CHEMOTACTIC FACTORS for CELL MIGRATION and AXON GUIDANCE, acting as chemoattractants for some cell types, and as chemorepellents for others.. netrin-1 defined as following: This gene plays a role in neurogenesis. It may also be involved in cell migration during development.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. Netrin-1 defined as following: This gene plays a role in neurogenesis. It may also be involved in cell migration during development.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species..", "label": "yes"} {"id": "converted_1394", "sentence1": "Are shadow enhancers associated with development?", "sentence2": "Critical developmental control genes sometimes contain \"shadow\" enhancers that can be located in remote positions, including the introns of neighboring genes, These results suggest that shadow enhancers represent a novel mechanism of canalization whereby complex developmental processes \"bring about one definite end-result regardless of minor variations in conditions\", Shadow enhancers flanking the HoxB cluster direct dynamic Hox expression in early heart and endoderm development., This suggests that they function as shadow enhancers to modulate the expression of genes from the HoxB complex during cardiac development. Regulatory analysis of the HoxA complex reveals that it also has enhancers in the 3' flanking region which contain RAREs and have the potential to modulate expression in endoderm and heart tissues, This suggests that they function as shadow enhancers to modulate the expression of genes from the HoxB complex during cardiac development., Recent reports have shown that developmental genes often possess multiple discrete enhancer modules that drive transcription in similar spatio-temporal patterns: primary enhancers located near the basal promoter and secondary, or 'shadow', enhancers located at more remote positions., Together, the similarities in their location, enhancer output, and dependence on retinoid signaling suggest that a conserved cis-regulatory cassette located in the 3' proximal regions adjacent to the HoxA and HoxB complexes evolved to modulate Hox gene expression during mammalian cardiac and endoderm development. , This suggests that they function as shadow enhancers to modulate the expression of genes from the HoxB complex during cardiac development.[SEP]Relations: petal development has relations: bioprocess_bioprocess with floral organ development, bioprocess_bioprocess with floral organ development, bioprocess_bioprocess with phyllome development, bioprocess_bioprocess with phyllome development. tRNA gene clustering has relations: bioprocess_bioprocess with chromosome organization, bioprocess_bioprocess with chromosome organization. heart elastic tissue has relations: anatomy_anatomy with mesoderm-derived structure, anatomy_anatomy with mesoderm-derived structure. endoderm has relations: anatomy_anatomy with endoderm of foregut-midgut junction, anatomy_anatomy with endoderm of foregut-midgut junction. Definitions: endoderm defined as following: The inner of the three germ layers of an embryo.. HoxA defined as following: A family of genes found in a cluster on the p arm of chromosome 7. These genes encode transcription factors that play a role in gene expression, morphogenesis, and cell differentiation.. introns defined as following: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. Hox gene defined as following: Genes that encode highly conserved TRANSCRIPTION FACTORS that control positional identity of cells (BODY PATTERNING) and MORPHOGENESIS throughout development. Their sequences contain a 180 nucleotide sequence designated the homeobox, so called because mutations of these genes often results in homeotic transformations, in which one body structure replaces another. The proteins encoded by homeobox genes are called HOMEODOMAIN PROTEINS.. developmental genes defined as following: Genes that determine the fate of a cell or CELLS in a region of the embryo during EMBRYONIC DEVELOPMENT.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"} {"id": "converted_2005", "sentence1": "Is Doxorubicin cardiotoxic?", "sentence2": "Doxorubicin (DOXO) is widely used to treat solid tumors. However, its clinical use is limited by side effects including serious cardiotoxicity due to cardiomyocyte damage. , The results provide direct evidence for the role of catalase in doxorubicin cardiotoxic responses., These results do not support the possibility that mitomycin C potentiates the acute cardiotoxic effects produced by doxorubicin., The anthracycline chemotherapeutic agent doxorubicin is converted by the enzyme carbonyl reductase 1 (CBR1) into its cardiotoxic metabolite doxorubicinol, The clinical efficiency of the highly potent antitumor agent doxorubicin is limited by cardiotoxic effects, Doxorubicin (DOX), a highly active chemotherapeutic drug, faces limitations in clinical application due to severe cardiotoxic effects (mainly through increased oxidative stress), Clinical uses of doxorubicin (DOX), a highly active anticancer agent, are limited by its severe cardiotoxic side effects associated with increased oxidative stress and apoptosis, Doxorubicin (DOX) and trastuzumab (TRZ) are highly effective chemotherapeutic agents in the breast cancer setting, limited by their cardiotoxic side effects, Twisting and ironing: doxorubicin cardiotoxicity by mitochondrial DNA damage., Cardiotoxic effects were reported in 15 (5%) of 291 children receiving treatment including doxorubicin., On the other hand, pretreatment of rats with hesperidin protected cardiac tissues against the cardiotoxic effects of doxorubicin as evidenced from amelioration of histopathological changes and normalization of cardiac biochemical parameters.Hesperidin may have a protective effect against DOX-induced cardiotoxicity., However, with cumulative doses, doxorubicin also is known to have cardiotoxic effects, including cardiomyopathy and heart failure., Methods of reducing or preventing doxorubicin-induced cardiotoxicity have been suggested, including an investigational doxorubicin analog, mitoxantrone ( Novantrone )., The most cardiotoxic drug, doxorubicin, is the most potent inducer of superoxide generation, while epirubicin, which is less cardiotoxic, has a relatively limited effect on superoxide production., The mechanism of doxorubicin cardiotoxicity is likely multifactorial and most importantly, the genetic factors predisposing to doxorubicin cardiotoxicity are unknown., As doxorubicin cardiotoxicity is considered irreversible, early detection of cardiotoxicity and prevention of overt heart failure is essential., Although there are monitoring guidelines for cardiotoxicity, optimal timing for early detection of subclinical doxorubicin cardiotoxicity is still obscure., Quercetin attenuates doxorubicin cardiotoxicity by modulating Bmi-1 expression., However, doxorubicin cardiotoxicity of the heart has largely limited its clinical use., Mitochondrial topoisomerase I (top1mt) is a novel limiting factor of doxorubicin cardiotoxicity., Doxorubicin-based chemotherapy induces cardiotoxicity, which limits its clinical application., he clinical use of doxorubicin (DOX) and other anthracyclines is limited by a dosage-dependent cardiotoxicity, which can lead to cardiomyopathy. , Besides its cardiotoxic effect, doxorubicin also elicits inflammatory effects in vivo. 7-Monohydroxyethylrutoside (monoHER) has recently been used as a protector against doxorubicin-induced cardiotoxicity in vivo., Doxorubicin is an effective antineoplastic agent, but it frequently causes dose-related cardiotoxic effects. , Among these analogs, idarubicin (4-demethoxy-daunorubicin) was shown to be less cardiotoxic than doxorubicin i, Verapamil has also been suggested to potentiate the cardiotoxicity of doxorubicin. , Doxorubicin treatment is associated with both acute and chronic cardiotoxicity. , cardiac effects of diclofenac sodium on doxorubicin-induced cardiomyopathy in rats[SEP]Relations: Doxorubicin has relations: drug_effect with Cardiogenic shock, drug_effect with Cardiogenic shock, drug_effect with Cardiomyopathy, drug_effect with Cardiomyopathy, contraindication with cardiomyopathy, contraindication with cardiomyopathy, drug_effect with Cardiomegaly, drug_effect with Cardiomegaly, drug_drug with Epirubicin, drug_drug with Epirubicin. Definitions: epirubicin defined as following: An anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA.. Doxorubicin defined as following: Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.. Verapamil defined as following: A calcium channel blocker that is a class IV anti-arrhythmia agent.. idarubicin defined as following: An orally administered anthracycline antineoplastic. The compound has shown activity against BREAST NEOPLASMS; LYMPHOMA; and LEUKEMIA.. heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. anthracycline defined as following: An antineoplastic antibiotic that is structurally similar to the benzoquinone ansamycin antibiotic geldanamycin. A geldanamycin analogue binds to HSP90, a chaperone protein that aids in the assembly, maturation, and folding of proteins. Subsequently, the function of HSP90 is inhibited, leading to the degradation and depletion of client proteins such as kinases and transcription factors involved with cell cycle regulation and signal transduction.. catalase defined as following: An oxidoreductase that catalyzes the conversion of HYDROGEN PEROXIDE to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in ACATALASIA.. Quercetin defined as following: A flavonol widely distributed in plants. It is an antioxidant, like many other phenolic heterocyclic compounds. Glycosylated forms include RUTIN and quercetrin.. cardiomyopathy defined as following: A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).. mitomycin C defined as following: An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.. trastuzumab defined as following: A humanized monoclonal antibody against the ERBB-2 RECEPTOR (HER2). As an ANTINEOPLASTIC AGENT, it is used to treat BREAST CANCER where HER2 is overexpressed.. hesperidin defined as following: A flavanone glycoside found in CITRUS fruit peels.. mitoxantrone defined as following: An anthracenedione-derived antineoplastic agent.. CBR1 defined as following: Carbonyl reductase [NADPH] 1 (277 aa, ~30 kDa) is encoded by the human CBR1 gene. This protein plays a role in the reduction of carbonyl compounds.. superoxide defined as following: Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.. rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. cardiotoxicity defined as following: Damage to the HEART or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.. cardiomyocyte defined as following: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).. solid tumors defined as following: A benign or malignant neoplasm arising from tissues that do not include fluid areas. Representative examples include epithelial neoplasms (e.g. lung carcinoma, prostate carcinoma, breast carcinoma, colon carcinoma), and neoplasms arising from the soft tissues and bones (e.g. leiomyosarcoma, liposarcoma, chondrosarcoma, osteosarcoma). Neoplasms originating from the blood or bone marrow (leukemias and myeloproliferative disorders) are not considered solid tumors..", "label": "yes"} {"id": "converted_2408", "sentence1": "Was saracatinib being considered as a treatment for Alzheimer's disease in November 2017?", "sentence2": "A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer's disease., Herein, we present a Phase Ib trial of the repurposed investigational drug AZD0530, a Src family kinase inhibitor specific for Fyn and Src kinase, for the treatment of patients with mild-to-moderate AD., The study was a 4-week Phase Ib multiple ascending dose, randomized, double-blind, placebo-controlled trial of AZD0530 in AD patients with Mini-Mental State Examination (MMSE) scores ranging from 16 to 26. A total of 24 subjects were recruited in three sequential groups, with each randomized to receive oral AZD0530 at doses of 50 mg, 100 mg, 125 mg, or placebo daily for 4 weeks. , AZD0530 is reasonably safe and well tolerated in patients with mild-to-moderate AD, achieving substantial central nervous system penetration with oral dosing at 100-125 mg. Targeting Fyn kinase may be a promising therapeutic approach in AD, and a larger Phase IIa clinical trial of AZD0530 for the treatment of patients with AD has recently launched.[SEP]Relations: Saracatinib has relations: drug_drug with Crizotinib, drug_drug with Crizotinib, drug_drug with Olaparib, drug_drug with Olaparib, drug_drug with Baricitinib, drug_drug with Baricitinib, drug_drug with Ibrutinib, drug_drug with Ibrutinib, drug_drug with Sunitinib, drug_drug with Sunitinib. Definitions: Src defined as following: Proto-oncogene tyrosine-protein kinase Src (536 aa, ~60 kDa) is encoded by the human SRC gene. This protein is involved in both receptor-mediated signal transduction and tyrosine phosphorylation.. saracatinib defined as following: An orally available 5-, 7-substituted anilinoquinazoline with anti-invasive and anti-tumor activities. Saracatinib is a dual-specific inhibitor of Src and Abl, protein tyrosine kinases that are overexpressed in chronic myeloid leukemia cells. This agent binds to and inhibits these tyrosine kinases and affects cell motility, cell migration, adhesion, invasion, proliferation, differentiation, and survival. Specifically, Saracatinib inhibits Src kinase-mediated osteoclast bone resorption.. Fyn defined as following: Tyrosine-protein kinase Fyn (537 aa, ~61 kDa) is encoded by the human FYN gene. This protein is involved in tyrosine phosphorylation, cytoskeleton remodeling and signal transduction.. Src kinase defined as following: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65..", "label": "yes"} {"id": "converted_1097", "sentence1": "Does thyroid hormone affect cardiac remodeling?", "sentence2": "The aim of this brief paper is to highlight new developments in understanding the cardioprotective role of thyroid hormone in reverting regulatory networks involved in adverse cardiac remodeling., Thyroid hormone receptor α1 (TRα1) is shown to be critical for the maturation of cardiomyocytes and for the cellular response to stress. TRα1 is altered during post ischemic cardiac remodeling but the physiological significance of this response is not fully understood. , AMI induces downregulation of thyroid hormone signaling and pharmacological inhibition of TRα1 further depresses post-ischemic cardiac function., These findings reveal crucial roles for Dio3 in heart function and remodeling, which may have pathophysiologic implications for human restrictive cardiomyopathy., TH administration after AMI prevented tissue hypothyroidism and resulted in decreased beta-MHC expression, increased wall thickening and normalized wallstress, while stretch-induced p38 MAPK activation was increased. We conclude that diabetes exacerbates post-ischemic cardiac remodeling and that tissue hypothyroidism may be involved in this response., Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction., It has been previously shown that regulators of physiological growth such as thyroid hormone (TH) can favorably remodel the post ischaemic myocardium., Acute myocardial infarction in diabetic rats results in TH receptor down-regulation with important physiological consequences. TH treatment prevents this response and improves cardiac hemodynamics., TH affects cardiac remodeling by limiting reperfusion injury, and, at later states, by inducing distinct changes in cardiac chamber geometry in a time-dependent manner., Furthermore, administration of TH can convert pathologic to physiologic hypertrophy. These effects are the result of favorable cellular remodeling., Thyroid hormone (TH) is critical in cardiac cell differentiation (regulating contractile proteins and cell geometry) and this effect could be potentially exploited therapeutically in reversing the process of de-differentiation which underlies postischemic cardiac remodeling. , TH treatment partially reverses cardiac dysfunction in rats with old myocardial infarction by favorably changing cardiac chamber geometry and expression of myosin isoforms. Thyroid hormone, unlike current treatments, appears to be a paradigm of therapeutic intervention which aims at restoring cardiac geometry and may prove new effective treatment for heart failure., Changes in thyroid hormone (TH)-TH receptors (TRs) axis occur in the course of post-infarction cardiac remodeling and seem to contribute to cardiac fetal phenotype. TH can \"rebuild\" the post-infarcted heart by preventing the fetal-like pattern of contractile proteins expression, normalizing wall tension, and optimizing cardiac chamber geometry. , TH, apart from its \"classical\" actions on cardiac contractility and heart rhythm, appears to regulate various intracellular signaling pathways related to stress responses and cardiac remodelling., More importantly, experimental and clinical studies demonstrate that TH can limit ischaemic injury, attenuate cardiac remodeling and improve cardiac hemodynamics. , Thyroid hormone attenuates cardiac remodeling and improves hemodynamics early after acute myocardial infarction in rats., Thyroid hormone administration early after infarction attenuates cardiac remodeling and significantly improves myocardial performance., It has previously been shown that thyroid hormone can reverse cardiac remodeling in failing hearts by reducing myocardial wall stress due to the unique changes induced in cardiac myocyte shape. [SEP]Relations: response to thyroid hormone has relations: bioprocess_bioprocess with response to hormone, bioprocess_bioprocess with response to hormone, bioprocess_bioprocess with cellular response to thyroid hormone stimulus, bioprocess_bioprocess with cellular response to thyroid hormone stimulus, bioprocess_bioprocess with response to thyroxine, bioprocess_bioprocess with response to thyroxine, bioprocess_protein with HPN, bioprocess_protein with HPN. thyroid hormone receptor binding has relations: molfunc_protein with OASL, molfunc_protein with OASL. Definitions: thyroid hormone defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs.. cardiac myocyte defined as following: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).. acute myocardial infarction defined as following: Necrosis of the myocardium, as a result of interruption of the blood supply to the area. It is characterized by a severe and rapid onset of symptoms that may include chest pain, often radiating to the left arm and left side of the neck, dyspnea, sweating, and palpitations.. TH defined as following: Tyrosine 3-monooxygenase (528 aa, ~59 kDa) is encoded by the human TH gene. This protein plays a role in the synthesis of dopamine from L-tyrosine.. human defined as following: Members of the species Homo sapiens.. rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. contractile proteins defined as following: Proteins which participate in contractile processes. They include MUSCLE PROTEINS as well as those found in other cells and tissues. In the latter, these proteins participate in localized contractile events in the cytoplasm, in motile activity, and in cell aggregation phenomena.. infarction defined as following: Formation of an infarct, which is NECROSIS in tissue due to local ISCHEMIA resulting from obstruction of BLOOD CIRCULATION, most commonly by a THROMBUS or EMBOLUS.. TRs defined as following: Catalysis of the reaction: ATP + L-threonine + tRNA(Thr) = AMP + diphosphate + L-threonyl-tRNA(Thr). [EC:6.1.1.3]. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. myocardial defined as following: Of or pertaining to the myocardium.. diabetes defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.. heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. Thyroid hormone receptor α1 defined as following: Specific high affinity binding proteins for THYROID HORMONES in target cells. They are usually found in the nucleus and regulate DNA transcription. These receptors are activated by hormones that leads to transcription, cell differentiation, and growth suppression. Thyroid hormone receptors are encoded by two genes (GENES, ERBA): erbA-alpha and erbA-beta for alpha and beta thyroid hormone receptors, respectively.. hypothyroidism defined as following: A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction.. AMI defined as following: MYOCARDIAL INFARCTION in which the anterior wall of the heart is involved. Anterior wall myocardial infarction is often caused by occlusion of the left anterior descending coronary artery. It can be categorized as anteroseptal or anterolateral wall myocardial infarction.. reperfusion injury defined as following: Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA..", "label": "yes"} {"id": "converted_2801", "sentence1": "Is ibudilast effective for multiple sclerosis?", "sentence2": "Ibudilast slowed brain atrophy in PPMS and SPMS patients in a multicenter phase 2b study., Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis., CONCLUSIONS: In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression., Specifically, the current evidence regarding treatment of progressive MS with ocrelizumab, simvastatin, ibudilast, alpha-lipoic acid, high-dose biotin, siponimod, and cell-based therapies are discussed., Based on our knowledge of pathophysiology, three therapeutic strategies are proposed: anti-inflammatory (ocrelizumab, siponimod…); remyelinating (opicinumab); and neuroprotective (high-dose biotin, ibudilast, simvastatin…). , Current article provides an overview of the pharmacology of IBD with a focus on preclinical and clinical data supporting its potential neuroprotective benefits for neurological conditions, including multiple sclerosis, neuropathic pain, medication overuse headache, stroke, opioid, alcohol and methamphetamine abuse., Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis., METHODS: SPRINT-MS is a randomized, placebo-controlled, phase II trial of ibudilast in patients with PMS., CONCLUSION: SPRINT-MS is designed to evaluate the safety and efficacy of ibudilast as a treatment for PMS while simultaneously validating five different imaging biomarkers as outcome metrics for use in future phase II proof-of-concept PMS trials., Ibudilast for the treatment of multiple sclerosis., AREAS COVERED: This article reviews various studies looking at ibudilast as a potential therapy for MS. It summarizes prior and current clinical trials of ibudilast in MS as well as its pharmacology.EXPERT OPINION: Although ibudilast has not been found to decrease the focal inflammatory activity in relapsing MS, it was shown to have an effect on preserving brain volume and disability progression. Ibudilast may have a role in the treatment of progressive MS phenotypes., Adverse events with ibudilast included gastrointestinal symptoms, headache, and depression.Include only the concept itself in the domain or value set. Do not include descendents of the concept.
.", "label": "yes"} {"id": "converted_172", "sentence1": "Is cytisine superior to nicotine replacement therapy for smoking cessation?", "sentence2": "The effectiveness of cytisine for continuous abstinence was superior to that of nicotine-replacement therapy at 1 week, 2 months, and 6 months. In a prespecified subgroup analysis of the primary outcome, cytisine was superior to nicotine-replacement therapy among women and noninferior among men., CONCLUSIONS: When combined with brief behavioral support, cytisine was found to be superior to nicotine-replacement therapy in helping smokers quit smoking, but it was associated with a higher frequency of self-reported adverse events.[SEP]Relations: Cytisine has relations: drug_protein with CHRNA6, drug_protein with CHRNA6, drug_protein with CHRNA4, drug_protein with CHRNA4, drug_protein with CHRNA3, drug_protein with CHRNA3, drug_protein with CHRNB2, drug_protein with CHRNB2, drug_protein with CHRNA7, drug_protein with CHRNA7.", "label": "yes"} {"id": "converted_2844", "sentence1": "Does epidural anesthesia for pain management during labor affect the Apgar score of the the infant?", "sentence2": " We retrospectively analyzed 93 consecutive single-pregnancy patients who underwent cesarean section with combined spinal-epidural anesthesia. The patients were divided into two groups, depending on the use of 6% HES 130/0.4: group A (461 ± 167 ml of saline-based HES was administered; 43 patients) and group B (HES not administered; 50 patients). The major outcome was umbilical cord chloride level at delivery. The volume infused from operating room admission until delivery was not significantly different between groups. The umbilical cord chloride level at delivery was statistically significantly higher in group A than in group B, but clinically similar (108 ± 2 vs. 107 ± 2 mmol/l, P = 0.02). No differences were observed in the Apgar score or other umbilical cord laboratory data at delivery (Na+, K+, pH, base excess), CONCLUSION\nSubarachnoid or epidural sufentanil, in the doses used in this study, associated with local anesthetics, had the same effect on the duration of labor after analgesia and in the Apgar score of newborns., CONCLUSION Subarachnoid or epidural sufentanil, in the doses used in this study, associated with local anesthetics, had the same effect on the duration of labor after analgesia and in the Apgar score of newborns.[SEP]Relations: Sufentanil has relations: drug_effect with Apnea, drug_effect with Apnea, drug_effect with Laryngeal stridor, drug_effect with Laryngeal stridor, drug_effect with Erythema, drug_effect with Erythema. idiopathic hypereosinophilic syndrome has relations: disease_phenotype_positive with Paresthesia, disease_phenotype_positive with Paresthesia, disease_phenotype_positive with Feeding difficulties in infancy, disease_phenotype_positive with Feeding difficulties in infancy. Definitions: sufentanil defined as following: An opioid analgesic that is used as an adjunct in anesthesia, in balanced anesthesia, and as a primary anesthetic agent.. HES defined as following: A rare hematologic disease characterized by eosinophilia without evidence of clonality persisting for at least six months, for which no underlying cause can be identified. The condition is associated with signs of organ damage and dysfunction. Clinical manifestations are highly variable, depending on the organ systems involved, and include rapidly developing, life-threatening cardiovascular or neurological complications..", "label": "no"} {"id": "converted_3832", "sentence1": "Is the Paramyxovirus geneome segmented, negative-sense RNA?", "sentence2": "The paramyxovirus family has a genome consisting of a single strand of negative sense RNA, The avian paramyxovirus type 1 (APMV-1), or Newcastle disease virus (NDV), comprise a diverse group of viruses with a single-stranded, negative-sense RNA genome., Members of the Paramyxoviridae such as measles, mumps, and parainfluenza viruses have pleomorphic, enveloped virions that contain negative-sense unsegmented RNA genomes., UNLABELLED: Mumps virus (MuV), a paramyxovirus containing a negative-sense nonsegmented RNA genome, is a human pathogen that causes an acute infection with symptoms ranging from parotitis to mild meningitis and severe encephalitis., UNLABELLED: Mumps virus (MuV) is a paramyxovirus with a negative-sense nonsegmented RNA genome., Paramyxoviridae, a large family of enveloped viruses harboring a nonsegmented negative-sense RNA genome, include important human pathogens as measles, mumps, respiratory syncytial virus (RSV), parainfluenza viruses, and henipaviruses, which cause some of the deadliest emerging zoonoses. There , Parainfluenza virus 5 (PIV5) is a member of the Paramyxoviridae family of membrane-enveloped viruses with a negative-sense RNA genome that is packaged and protected by long filamentous nucleocapsid-helix structures (RNPs). , The paramyxovirus genome, a nonsegmented, negative-polarity, single-stranded RNA of approximately 15 kb, contains six transcription units flanked at the 3' and 5' ends by a short (approximately 50- to 60-nucleotide) extracistronic sequence, dubbed the positive and negative leader regions. These, The replication of nonsegmented minus-strand RNA genomes, like that of Sendai paramyxovirus (SeV), are controlled by the short leader regions present at each end of the linear genomes and antigenomes; the left and right promoters (PL and PR), respectively. Wil, UNLABELLED: Mumps virus (MuV), a paramyxovirus containing a negative-sense nonsegmented RNA genome, is a human pathogen that causes an acute infection with symptoms ranging from parotitis to mild meningitis and severe enc, s viral glycoprotein cytoplasmic domains may play a role in this coordination, we have investigated the importance of the hemagglutinin-neuraminidase (HN) protein cytoplasmic domain in the assembly of the nonsegmented negative-strand RNA paramyxovirus simian virus 5 (SV5). By, Beilong virus, a novel paramyxovirus with the largest genome of non-segmented negative-stranded RNA viruses., The paramyxovirus genome, a nonsegmented, negative-polarity, single-stranded RNA of approximately 15 kb, contains six transcription units flanked at the 3' and 5' ends by a short (approximately 50- to 60-nucleotide) extracistronic sequence, dubbed the positive and negative leader regions., Paramyxovirus particles are pleomorphic, with a lipid envelope, nonsegmented RNA genomes of negative polarity, and densely packed glycoproteins on the virion surface., An alternative method to determine the 5' extremities of non-segmented, negative sense RNA viral genomes using positive replication intermediate 3' tailing: application to two members of the Paramyxoviridae family., Simian parainfluenza virus 5 (SV5) is a prototype of the Paramyxoviridae family of nonsegmented negative-sense RNA viruses., Human metapneumovirus (HMPV), a single-stranded negative-sense RNA virus belonging to the family Paramyxoviridae, is associated with respiratory tract illness, primarily in young children and persons with underlying disease.[SEP]Relations: Parotitis has relations: disease_phenotype_positive with sarcoidosis, disease_phenotype_positive with sarcoidosis. Protein S human has relations: drug_drug with Deferasirox, drug_drug with Deferasirox, drug_drug with Dactinomycin, drug_drug with Dactinomycin, drug_drug with Interferon beta-1b, drug_drug with Interferon beta-1b, drug_drug with Ximelagatran, drug_drug with Ximelagatran. Definitions: parotitis defined as following: INFLAMMATION of the PAROTID GLAND.. Human metapneumovirus defined as following: A species of nonsegmented, negative-strand ssRNA viruses in the family Paramyxoviridae. Infections with human metapneumovirus can cause upper and lower respiratory tract infections in patients of all ages. This virus is second only to respiratory syncytial virus as the most commonly identified cause of pediatric lower respiratory illness.. human defined as following: Members of the species Homo sapiens.. genome defined as following: Anatomical set of genes in all the chromosomes.. paramyxovirus defined as following: A single-stranded, negative-sense RNA virus of the Paramyxoviridae family.. respiratory syncytial virus defined as following: The type species of PNEUMOVIRUS and an important cause of lower respiratory disease in infants and young children. It frequently presents with bronchitis and bronchopneumonia and is further characterized by fever, cough, dyspnea, wheezing, and pallor.. encephalitis defined as following: Inflammation of the BRAIN due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see ENCEPHALITIS, VIRAL) are a relatively frequent cause of this condition.. PR defined as following: Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives.. PL defined as following: Homeobox protein Hox-A10 (410 aa, ~42 kDa) is encoded by the human HOXA10 gene. This protein plays a role in embryonic pattern formation.. Parainfluenza virus 5 defined as following: A species of RUBULAVIRUS originally isolated from cultured primary monkey cells. Its natural host is the DOG in which it causes kennel cough, but it can also infect humans.. viruses defined as following: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells.. henipaviruses defined as following: A genus of enveloped, pleomorphically spherical viruses in the family Paramyxoviridae. The genome is composed of a linear single-strand of negative sense RNA. The Henipavirus natural reservoir is considered to be fruit bats of the Pteropodidae family and cause influenza-like illness in humans.. Newcastle disease virus defined as following: The most well known avian paramyxovirus in the genus AVULAVIRUS and the cause of a highly infectious pneumoencephalitis in fowl. It is also reported to cause CONJUNCTIVITIS in humans. Transmission is by droplet inhalation or ingestion of contaminated water or food..", "label": "no"} {"id": "converted_1340", "sentence1": "Are there enhancer RNAs (eRNAs)?", "sentence2": "active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription, eRNAs may then facilitate enhancer-promoter interaction or activate promoter-driven transcription, Enhancer RNAs: a class of long noncoding RNAs synthesized at enhancers, Enhancer RNAs and regulated transcriptional programs, enhancers have been found to be broadly transcribed, resulting in the production of enhancer-derived RNAs, or eRNAs, The emerging roles of eRNAs in transcriptional regulatory networks, we found certain enhancer RNAs (eRNAs) regulate chromatin accessibility of the transcriptional machinery at loci encoding master regulators of myogenesis (i.e., MyoD/MyoG), thus suggesting their significance and site-specific impact in cellular programming, Enhancer RNAs: the new molecules of transcription, the discovery that distal regulatory elements known as enhancers are transcribed and such enhancer-derived transcripts (eRNAs) serve a critical function in transcriptional activation has added a new dimension to transcriptional regulation, eRNAs reach the heart of transcription, Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation., Since the discovery that many transcriptional enhancers are transcribed into long noncoding RNAs termed \"enhancer RNAs\" (eRNAs), their putative role in enhancer function has been debated., Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs)., Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established., In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs)., In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). , A subset of enhancers are occupied by RNA polymerase II (RNAP II) and transcribed to produce long non-coding RNAs termed eRNAs. , Very recent evidence has indicted that some eRNAs play a role in initiating or activating transcription, possibly by helping recruit and/or stabilize binding of the general transcription machinery to the proximal promoter of their target genes. , In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation. , Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4. The level of eRNA expression at neuronal enhancers positively correlates with the level of messenger RNA synthesis at nearby genes, suggesting that eRNA synthesis occurs specifically at enhancers that are actively engaged in promoting mRNA synthesis., A function of CBP at enhancers may be to recruit RNA polymerase II (RNAPII), as we also observed activity-regulated RNAPII binding to thousands of enhancers. Notably, RNAPII at enhancers transcribes bi-directionally a novel class of enhancer RNAs (eRNAs) within enhancer domains defined by the presence of histone H3 monomethylated at lysine 4., Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established. Here we show that eRNAs facilitate the transition of paused RNA polymerase II (RNAPII) into productive elongation by acting as a decoy for the negative elongation factor (NELF) complex upon induction of immediate early genes (IEGs) in neurons., Recent studies have disclosed the function of enhancer RNAs (eRNAs), which are long non-coding RNAs transcribed from gene enhancer regions, in transcriptional regulation., Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription., Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers,, In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation., Recent studies have revealed that active enhancers are transcribed, producing a class of noncoding RNAs called enhancer RNAs (eRNAs). eRNAs are distinct from long noncoding RNAs (lncRNAs), but these two species of noncoding RNAs may share a similar role in the activation of mRNA transcription.[SEP]Relations: mRNA transcription has relations: bioprocess_protein with EREG, bioprocess_protein with EREG, bioprocess_protein with HIPK3, bioprocess_protein with HIPK3, bioprocess_bioprocess with mRNA transcription by RNA polymerase II, bioprocess_bioprocess with mRNA transcription by RNA polymerase II, bioprocess_protein with HSF1, bioprocess_protein with HSF1. RNA localization to chromatin has relations: bioprocess_protein with HNRNPU, bioprocess_protein with HNRNPU. Definitions: RNA polymerase II defined as following: A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC 2.7.7.6.. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. histone H3 defined as following: Histone H3 is a core subunit of the eukaryotic nucleosome complex. Histones are basic nuclear proteins responsible for the nucleosome structure of chromatin. Repeating nucleosome units contain two molecules each of Histones H2A, H2B, H3, and H4 that form an octamer complex around which approximately 146 base pairs of DNA is wrapped. Linker Histone H1 interacts with DNA between nucleosome units in mediating chromatin compaction into higher order structures. (NCI). promoter defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. mRNA transcription defined as following: The cellular synthesis of messenger RNA (mRNA) from a DNA template. [GOC:jl]. molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds..", "label": "yes"} {"id": "converted_3686", "sentence1": "Does saracatinib promote oncogenesis?", "sentence2": "Antitumor activity of saracatinib (AZD0530), a c-Src/Abl kinase inhibitor, alone or in combination with chemotherapeutic agents in gastric cancer., We evaluated the antitumor effect of a c-Src/Abl kinase inhibitor, saracatinib (AZD0530), alone or combined with chemotherapeutic agents in gastric cancer cell lines and a NCI-N87 xenograft model. Among 10 gastric cancer cell lines, saracatinib specifically inhibited the growth and migration/invasion of SNU216 and NCI-N87 cells. Saracatinib blocked the Src/FAK, HER family, and oncogenic signaling pathways, and it induced G(1) arrest and apoptosis in SNU216 and NCI-N87 cells. , Consistent with our in vitro findings, cotreatment with saracatinib and 5-FU resulted in enhanced antitumor activity in the NCI-N87 xenografts. These data indicate that the inhibition of Src kinase activity by saracatinib alone or in combination with other agents can be a strategy to target gastric cancer.[SEP]Relations: Saracatinib has relations: drug_drug with Tofacitinib, drug_drug with Tofacitinib, drug_drug with Sonidegib, drug_drug with Sonidegib, drug_drug with Cobimetinib, drug_drug with Cobimetinib, drug_drug with Doxazosin, drug_drug with Doxazosin, drug_drug with Palbociclib, drug_drug with Palbociclib. Definitions: HER defined as following: A Niger-Congo Bantu language spoken by the Herero and Mbanderu peoples in Namibia and Botswana.. Saracatinib defined as following: An orally available 5-, 7-substituted anilinoquinazoline with anti-invasive and anti-tumor activities. Saracatinib is a dual-specific inhibitor of Src and Abl, protein tyrosine kinases that are overexpressed in chronic myeloid leukemia cells. This agent binds to and inhibits these tyrosine kinases and affects cell motility, cell migration, adhesion, invasion, proliferation, differentiation, and survival. Specifically, Saracatinib inhibits Src kinase-mediated osteoclast bone resorption.. gastric cancer defined as following: A primary or metastatic malignant neoplasm involving the stomach.. Src kinase defined as following: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.. 5-FU defined as following: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.. saracatinib defined as following: An orally available 5-, 7-substituted anilinoquinazoline with anti-invasive and anti-tumor activities. Saracatinib is a dual-specific inhibitor of Src and Abl, protein tyrosine kinases that are overexpressed in chronic myeloid leukemia cells. This agent binds to and inhibits these tyrosine kinases and affects cell motility, cell migration, adhesion, invasion, proliferation, differentiation, and survival. Specifically, Saracatinib inhibits Src kinase-mediated osteoclast bone resorption..", "label": "no"} {"id": "converted_1929", "sentence1": "Can NADPH oxidase be inhibited by apocynin and diphenylene iodonium?", "sentence2": "Ang II treatment also led to a significant increment in intracellular reactive oxygen species generation, which could be fully abolished by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors apocynin or diphenylene iodonium, indicating that Ang II enhanced oxidative stress via a NADPH oxidase-dependent manner., NOX inhibitors (diphenylene iodonium (DPI) or apocynin) were able to achieve similar results to that of ML-7 except no effect on MLCK activity and MLC20 phosphorylation. , Significant reductions of AII effects on podocyte TRPC6 were also observed after pretreatment with NADPH oxidase inhibitors apocynin or diphenylene iodonium (DPI). , Furthermore, inhibition of NOX-mediated ROS production with apocynin, diphenylene iodonium (DPI) or NOX2 docking sequence (Nox2ds)-tat peptide during these first 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation. , Remarkably, Ang-II induced reactive oxygen species (ROS) via a NAD(P)H oxidase-dependent mechanism, as shown by inhibition of ROS production via the NAD(P)H oxidase inhibitors diphenylene iodonium (DPI) and apocynin. , Moreover, NADPH oxidase activation by beta CD (145.5+/-9.0%; control: 98.6+/-1.6%) was also abrogated by the NADPH oxidase inhibitors apocynin (100.4+/-3.2%) and diphenylene iodonium (9.5+/-3.3%)., We used structurally diverse NADPH oxidase inhibitors, aminoethyl-benzenesulfonylfluoride (AEBSF, 100-1000microM), apocynin (100-1000microM), and diphenylene iodonium (DPI, 3-30microM), to inhibit intrinsic NADPH oxidase activity in N27 cells., Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol., With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium., The contractile responses to U46619 in isolated PA were inhibited by PEG-catalase and the NADPH oxidase inhibitors diphenylene iodonium (DPI) and apocynin., The effects of diphenylene iodonium (DPI) and apocynin, inhibitors of NADPH oxidase, on key parameters of PSC activation were evaluated in vitro., These effects could be inhibited by diphenylene iodonium and apocynin, indicating a self-cycle regulated by NADPH oxidase in microglial activation in response to oAâ., Diphenylene iodonium is an inhibitor of the respiratory burst-generating NADPH oxidase of phagocytes., NADPH oxidase inhibitors [diphenylene iodonium (DPI) and apocynin (4-hydroxy-3-methoxy-acetophenone)] prevented the microglial activation induced by oAâ, suggesting that NADPH oxidase activation was involved in microglial activation., In addition, inhibitors of NADPH oxidase (diphenylene iodonium or apocynin) also prevented microglia proliferation, suggesting that this may be the source of hydrogen peroxide., Inhibitors of NADPH oxidase (diphenylene iodonium, apocynin, D-(+)-neopterine) also significantly blunted the generation of reactive oxygen species, activation of K(+), Cl(-)-cotransport and apoptosis induced by N-ethylmaleimide., With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium., NADPH-dependent superoxide production by the solubilized oxidase of neutrophils was inhibited 36% by diphenylene iodonium at a 1:1 stoichiometry with the enzyme flavoprotein content., These effects could be inhibited by diphenylene iodonium and apocynin, indicating a self-cycle regulated by NADPH oxidase in microglial activation in response to oAβ, Moreover, CSE-regulated COX-2, PGE(2), and IL-6 generation was inhibited by pretreatment with TLR4 Ab; inhibitors of c-Src (PP1), NADPH oxidase (diphenylene iodonium chloride and apocynin), p38 MAPK (SB202190), MEK1/2 (U0126), JNK1/2 (SP600125), and NF-kappaB (helenalin); a ROS scavenger (N-acetyl-l-cysteine); and transfection with siRNA of TLR4, MyD88, TRAF6, Src, p47(phox), p38, p42, JNK2, or p65, Treatment of the cells with the NADPH oxidase inhibitors, apocynin and diphenylene iodonium, inhibited these effects, With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium, UVB irradiation generated ROS in a dose-dependent manner, and this was significantly inhibited by diphenylene iodonium (DPI), apocynin (Apo) and neopterine (Neo), inhibitors of the NADPH oxidase, and indomethacin (Indo), a cyclooxygenase (COX) inhibitor, but not by the mitochondrial electron transport inhibitors and other cytosolic enzyme inhibitors, In RBA-1 cells, JEV induced MMP-9 expression and promoter activity, which was inhibited by pretreatment with inhibitors of NADPH oxidase (diphenylene iodonium chloride or apocynin), MAPKs (U0126, SB203580 or SP600125) and a ROS scavenger (N-acetylcysteine), or transfection with siRNAs of p47(phox) , ERK1, JNK2 and p38, Such discharge of Dectin-1-reactive β-glucan from macrophage cells was inhibited by either NADPH oxidase inhibitors (apocynin and diphenylene iodonium) or radical scavengers (N-acetyl cysteine and MCI-186), The contractile responses to U46619 in isolated PA were inhibited by PEG-catalase and the NADPH oxidase inhibitors diphenylene iodonium (DPI) and apocynin, ANG II further increased superoxide production in LP only, and this was inhibited by coincubation with diphenylene iodonium or apocynin (inhibitor of NADPH oxidase complex), Our results showed that IL-1beta enhanced HTSMCs-monocyte adhesion through up-regulation of VCAM-1, which was inhibited by pretreatment with selective inhibitors of PKCalpha (Gö6976), c-Src (PP1), NADPH oxidase [diphenylene iodonium (DPI) and apocynin (APO)], intracellular calcium chelator (BAPTA/AM), PI-PLC (U73122), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (garcinol), NF-kappaB (Bay11-7082), HDAC (trichostatin A), and ROS scavenger [N-acetyl-L-cysteine (NAC)] or transfection with siRNAs of MyD88, PKCalpha, Src, p47(phox), p300, and HDAC4., Here we show that cAMP-dependent decidualization can be attenuated or enhanced upon treatment of primary cultures with a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (diphenylen iodonium) or activator (apocynin), respectively. , With the use of dihydroethidium as a superoxide indicator, C(2)-ceramide was found to increase superoxide production in the endothelial cells of small coronary arteries, which was inhibited by the NADPH oxidase inhibitors N-vanillylnonanamide, apocynin, and diphenylene iodonium. , The inhibition of NAD(P)H oxidase by apocynin and diphenylene iodonium, and of the mitochondrial electron transport system at complex II by thenoyltrifluoroacetone (TTFA), significantly inhibited both AGE-induced ROS production and VCAM-1 expression, whereas these effects were potentiated by rotenone and antimycin A, specific inhibitors of mitochondrial complex I and III, respectively. , Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol. , Treatment of the cells with the NADPH oxidase inhibitors, apocynin and diphenylene iodonium, inhibited these effects. , The G6PD inhibitor DHEA and the inhibitors of NADPH oxidase apocynin and diphenylene iodonium (DPI) prevented both superoxide generation and capacitation in human spermatozoa, but whereas DPI and DHEA inhibited PPP, apocynin did not influence it, suggesting that PPP activation during capacitation is not a response to increased oxidative stress but exerts a role by supplying reducing equivalents to oxygen., Ang II induced a time-dependent increase in Rac1 activation and O(2)(*-) production in Neuro-2A cells, and this was abolished by pretreatment with AdN17Rac1 or the NADPH oxidase inhibitors apocynin or diphenylene iodonium. , Paraquat-induced ROS production was inhibited by NADPH oxidase inhibitors, apocynin and diphenylene iodonium (DPI), but not the xanthine/xanthine oxidase inhibitor, allopurinol., In RBA-1 cells, JEV induced MMP-9 expression and promoter activity, which was inhibited by pretreatment with inhibitors of NADPH oxidase (diphenylene iodonium chloride or apocynin), MAPKs (U0126, SB203580 or SP600125) and a ROS scavenger (N-acetylcysteine), or transfection with siRNAs of p47(phox) , ERK1, JNK2 and p38., These effects could be inhibited by diphenylene iodonium and apocynin, indicating a self-cycle regulated by NADPH oxidase in microglial activation in response to oAβ., Treatment of the cells with the NADPH oxidase inhibitors, apocynin and diphenylene iodonium, inhibited these effects., UVB irradiation generated ROS in a dose-dependent manner, and this was significantly inhibited by diphenylene iodonium (DPI), apocynin (Apo) and neopterine (Neo), inhibitors of the NADPH oxidase, and indomethacin (Indo), a cyclooxygenase (COX) inhibitor, but not by the mitochondrial electron transport inhibitors and other cytosolic enzyme inhibitors., Such discharge of Dectin-1-reactive β-glucan from macrophage cells was inhibited by either NADPH oxidase inhibitors (apocynin and diphenylene iodonium) or radical scavengers (N-acetyl cysteine and MCI-186)., Our results showed that IL-1beta enhanced HTSMCs-monocyte adhesion through up-regulation of VCAM-1, which was inhibited by pretreatment with selective inhibitors of PKCalpha (Gö6976), c-Src (PP1), NADPH oxidase [diphenylene iodonium (DPI) and apocynin (APO)], intracellular calcium chelator (BAPTA/AM), PI-PLC (U73122), CaM (calmidazolium chloride), CaM kinase II (KN62), p300 (garcinol), NF-kappaB (Bay11-7082), HDAC (trichostatin A), and ROS scavenger [N-acetyl-L-cysteine (NAC)] or transfection w, Moreover, CSE-regulated COX-2, PGE(2), and IL-6 generation was inhibited by pretreatment with TLR4 Ab; inhibitors of c-Src (PP1), NADPH oxidase (diphenylene iodonium chloride and apocynin), p38 MAPK (SB202190), MEK1/2 (U0126), JNK1/2 (SP600125), and NF-kappaB (helenalin); a ROS scavenger (N-acetyl-l-cysteine); and transfection with siRNA of TLR4, MyD88, TRAF6, Src, p47(phox), p38, p42, JNK2, or p65., The use of diphenylene iodonium, an inhibitor of NADPH oxidase, to investigate the antimicrobial action of human monocyte derived macrophages., NADPH oxidase inhibitors [diphenylene iodonium (DPI) and apocynin (4-hydroxy-3-methoxy-acetophenone)] prevented the microglial activation induced by oAβ, suggesting that NADPH oxidase activation was involved in microglial activation., Furthermore, inhibition of NOX-mediated ROS production with apocynin, diphenylene iodonium (DPI) or NOX2 docking sequence (Nox2ds)-tat peptide during these first 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation., We compared the pharmacological profiles of the commonly used NADPH oxidase inhibitors, diphenylene iodonium (DPI), apocynin and 4-(2-amino-ethyl)-benzolsulphonyl-fluoride (AEBSF), as well as the novel triazolo pyrimidine VAS3947., IL-1beta and TNF-alpha rapidly stimulated the rate of hydrogen peroxide produced by isolated microglia, and this was inhibited by diphenylene iodonium, implying that the cytokines were acting directly on microglia to stimulate the NADPH oxidase., The fractions achieved the same effects that known NADPH oxidase inhibitors, such as diphenylene iodonium and apocynin, but they presented better hydrosolubility., Ang II induced a time-dependent increase in Rac1 activation and O(2)(*-) production in Neuro-2A cells, and this was abolished by pretreatment with AdN17Rac1 or the NADPH oxidase inhibitors apocynin or diphenylene iodonium.[SEP]Relations: NADPH oxidase complex has relations: cellcomp_protein with NOX4, cellcomp_protein with NOX4, cellcomp_protein with NOX4, cellcomp_protein with NOX4, cellcomp_protein with NOX3, cellcomp_protein with NOX3, cellcomp_protein with NOX3, cellcomp_protein with NOX3, cellcomp_protein with CYBA, cellcomp_protein with CYBA. Definitions: p38 defined as following: Human MAPK14 wild-type allele is located within 6p21.3-p21.2 and is approximately 83 kb in length. This allele, which encodes mitogen-activated protein kinase 14 protein, plays a role in both the production of certain cytokines and the regulation of cellular signaling in response to environmental stress, lipopolysaccharide and pro-inflammatory cytokines.. IL-6 defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine interleukin-6 (IL-6) with antiapoptotic, proinflammatory, antiinflammatory, proproliferative and proangiogenic activities. IL-6 binds to its receptor (IL-6R), activating a receptor-CD130 receptor complex; the CD130 portion of the complex is a signal transduction protein that activates JAK kinases and Ras-mediated signaling pathways, which in turn activate downstream signaling pathways, resulting in the activation of various transcription factors (STAT, ELK-1, NF-IL-6, etc.) and gene transcription. The physiological effects of IL-6 are complex and varied and include hematopoietic, pyrogenic and thermogenic, proinflammatory, antiinflammatory, proproliferative (anti-apoptotic), and angiogenic effects.. rotenone defined as following: A botanical insecticide that is an inhibitor of mitochondrial electron transport.. thenoyltrifluoroacetone defined as following: Chelating agent and inhibitor of cellular respiration.. AII defined as following: Human NLRP3 wild-type allele is located in the vicinity of 1q44 and is approximately 33 kb in length. This allele, which encodes NACHT, LRR and PYD domains-containing protein 3, is involved in the regulation of both apoptosis and inflammation. Mutation of the gene is associated with familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurological cutaneous and articular syndrome.. cyclooxygenase defined as following: An enzyme that converts arachidonic acid into biologically active prostanoids, such as prostaglandins, prostacyclins, and thromboxanes.. DHEA defined as following: A synthetic form of dehydroepiandrosterone with potential chemopreventive activity. Produced endogenously, dehydroepiandrosterone (DHEA) is an intermediate in the conversion of cholesterol to androgens and estrogens. Although the mechanisms of action of exogenously administered DHEA have not been fully illuminated, they may result in both direct and indirect physiologic effects. Direct effects include GABA-a receptor complex and NMDA receptor modulation, and enhanced pancreatic beta cell insulin secretion and antiglucocorticoid activities. (NCI04). NAD(P)H oxidase defined as following: A family of membrane-associated flavoprotein NADPH-dependent oxidoreductases that catalyze the univalent reduction of OXYGEN to create SUPEROXIDES. Structurally, they are characterized by six N-terminal transmembrane ALPHA-HELICES, a FLAVIN-ADENINE DINUCLEOTIDE (FAD)-binding region, and a C-terminal NADPH-binding region. They are expressed primarily by EPITHELIAL CELLS in gut, kidney, colon, and smooth muscle tissues, as well as GRANULOCYTES and function to transfer electrons across membranes to molecular oxygen. Defects in the production of superoxide ions by some NADPH oxidases result in GRANULOMATOUS DISEASE, CHRONIC.. p300 defined as following: Human EP300 wild-type allele is located in the vicinity of 22q13.2 and is approximately 88 kb in length. This allele, which encodes the histone acetyltransferase p300 protein, is involved in both cyclic-AMP driven transcriptional activation and the cellular response to hypoxia.. superoxide defined as following: Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.. PE defined as following: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to an ethanolamine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and ethanolamine and 2 moles of fatty acids.. ERK1 defined as following: A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.. N-acetyl-l-cysteine defined as following: The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. antimycin A defined as following: An antibiotic substance produced by Streptomyces species. It inhibits mitochondrial respiration and may deplete cellular levels of ATP. Antimycin A1 has been used as a fungicide, insecticide, and miticide. (From Merck Index, 12th ed). NADPH oxidase complex defined as following: A membrane-bound enzyme complex expressed in neutrophils or in cells of the vasculature and thyroid that faces the extracellular space and catalyzes the production of a superoxide free radical by transferring one electron to oxygen from (nicotinamide adenine dinucleotide phosphate) NADPH. In neutrophils, the superoxide is generated as part of the respiratory burst involved in immune responses.. complex II defined as following: A heterotetrameric enzyme complex found in the inner mitochondrial membrane. This protein complex catalyzes the oxidation of succinate and reduction of ubiquinone and plays a role in both the citric acid cycle and the electron transport chain.. ROS defined as following: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.. MyD88 defined as following: Myeloid differentiation primary response protein MyD88 (296 aa, ~33 kDa) is encoded by the human MYD88 gene. This protein is involved in the modulation of signaling pathways that stimulate the innate immune response.. indomethacin defined as following: A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES.. MMP-9 defined as following: An endopeptidase that is structurally similar to MATRIX METALLOPROTEINASE 2. It degrades GELATIN types I and V; COLLAGEN TYPE IV; and COLLAGEN TYPE V.. allopurinol defined as following: A XANTHINE OXIDASE inhibitor that decreases URIC ACID production. It also acts as an antimetabolite on some simpler organisms.. PPP defined as following: A chronic inflammatory disorder that generally occurs in adulthood and is characterized by sterile pustules intermingled with scaly erythemas, vesicles and hyperkeratosis occurring at distinct sites on the palms and soles. It is thought to be an autoimmune disorder precipitated by several factors, including local infection, and smoking.. HDAC defined as following: Human HDAC9 wild-type allele is located in the vicinity of 7p21.1 and is approximately 910 kb in length. This allele, which encodes histone deacetylase 9 protein, is involved in the modification of histones.. PI-PLC defined as following: Human PDIA3 wild-type allele is located in the vicinity of 15q15 and is approximately 27 kb in length. This allele, which encodes protein disulfide-isomerase A3 protein, plays a role in both the rearrangement of protein disulfide bonds and antigen presentation.. p38 MAPK defined as following: A 38-kDa mitogen-activated protein kinase that is abundantly expressed in a broad variety of cell types. It is involved in the regulation of cellular stress responses as well as the control of proliferation and survival of many cell types. The kinase activity of the enzyme is inhibited by the pyridinyl-imidazole compound SB 203580.. Rac1 defined as following: This gene is involved in both cell motility and signal transduction.. N-ethylmaleimide defined as following: A sulfhydryl reagent that is widely used in experimental biochemical studies.. endothelial cells defined as following: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.. VCAM-1 defined as following: Cytokine-induced cell adhesion molecule present on activated endothelial cells, tissue macrophages, dendritic cells, bone marrow fibroblasts, myoblasts, and myotubes. It is important for the recruitment of leukocytes to sites of inflammation. (From Pigott & Power, The Adhesion Molecule FactsBook, 1993, p154). phagocytes defined as following: Cells that can carry out the process of PHAGOCYTOSIS.. hydrogen peroxide defined as following: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.. Neo defined as following: The NEO Gene confers resistance to the aminoglycoside antibiotic neomycin. NEO is widely used in genetic research because of the easily selectable phenotype.. JNK2 defined as following: Human MAPK9 wild-type allele is located within 5q35 and is approximately 45 kb in length. This allele, which encodes mitogen-activated protein kinase 9 protein, is involved in the activation of nuclear transcription factors in response to environmental stress and pro-inflammatory cytokines, stabilization of the p53 tumor suppressor protein and differentiation of T-helper cells.. HDAC4 defined as following: This gene is involved in chromatin remodeling, repression of gene expression and myoblast differentiation.. CaM kinase II defined as following: A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.. TNF-alpha defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine tumor necrosis factor-alpha with antineoplastic properties. Tumor necrosis factor-alpha binds to and activates \"death receptors\" on the cell surface, resulting in apoptosis and cell death by the p53-independent extrinsic pathway. This agent also disrupts tumor vascularization. (NCI04). COX-2 defined as following: Human PTGS2 wild type allele is located within 1q25.2-q25.3 and is approximately 9 kb in length. This allele, which encodes prostaglandin G/H synthase 2 protein, plays a role in the stimulation of inflammatory responses.. Src defined as following: Proto-oncogene tyrosine-protein kinase Src (536 aa, ~60 kDa) is encoded by the human SRC gene. This protein is involved in both receptor-mediated signal transduction and tyrosine phosphorylation.. TRAF6 defined as following: A signal transducing tumor necrosis factor receptor associated factor that is involved in regulation of NF-KAPPA B signalling and activation of JNK MITOGEN-ACTIVATED PROTEIN KINASES.. TLR4 defined as following: Human TLR4 wild-type allele is located within 9q32-q33 and is approximately 11 kb in length. This allele, which encodes toll-like receptor 4 protein, is involved in pathogen recognition, signal transduction and innate immunity. Mutations in the gene are associated with differences in LPS responsiveness.. c-Src defined as following: Human SRC wild-type allele is located within 20q12-q13 and is approximately 61 kb in length. This allele, which encodes proto-oncogene tyrosine-protein kinase Src protein, plays a role in signal transduction pathways involved in the inhibition of endothelial cell apoptosis, regulation of the actin cytoskeleton, and the production of gonadotropins in pituitary cells. An allelic variant of the SRC gene, which produces a truncated, inactive protein, is associated with the development and metastasis of both breast and colon cancer.. IL-1beta defined as following: An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. neutrophils defined as following: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.. microglia defined as following: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.. PA defined as following: A SI derived unit of pressure equivalent to one newton per square meter or 10 bars or to 1.45x10E-4 pounds per square inch.. cytosolic defined as following: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.. PSC defined as following: A type of cataract that forms in the most posterior cortical layer of the lens, directly under the lens capsule. This type of cataract tends to occur in younger patients than cortical or nuclear sclerotic cataracts.. nicotinamide adenine dinucleotide phosphate defined as following: Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5'-phosphate (NMN) coupled by pyrophosphate linkage to the 5'-phosphate adenosine 2',5'-bisphosphate. It serves as an electron carrier in a number of reactions, being alternately oxidized (NADP+) and reduced (NADPH). (Dorland, 27th ed). mitochondrial complex I defined as following: A complex of over 40 proteins found in the inner mitochondrial membrane. This protein complex catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q10) and plays a role in the initiation of the mitochondrial electron transport chain.. NF-kappaB defined as following: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA..", "label": "yes"} {"id": "converted_1542", "sentence1": "Is thyroid hormone therapy indicated in patients with heart failure?", "sentence2": "Patients with chronic heart failure and subclinical hypothyroidism significantly improved their physical performance when normal TSH levels were reached., Early and sustained physiological restoration of circulating L-T3 levels after MI halves infarct scar size and prevents the progression towards heart failure. This beneficial effect is likely due to enhanced capillary formation and mitochondrial protection., These data indicate that T(3) replacement to euthyroid levels improves systolic function and tends to improve diastolic function, potentially through changes in myocardial gene expression., In these patients, the administration of synthetic triiodothyronine (T(3)) was well tolerated and induced significant improvement in cardiac function without increased heart rate and metabolic demand., In DC patients, short-term synthetic L-T(3) replacement therapy significantly improved neuroendocrine profile and ventricular performance., Triiodothyronine was well tolerated without episodes of ischemia or clinical arrhythmia. There was no significant change in heart rate or metabolic rate and there was minimal increase in core temperature. Cardiac output increased with a reduction in systemic vascular resistance in patients receiving the largest dose, consistent with a peripheral vasodilatory effect.[SEP]Relations: Congestive heart failure has relations: drug_effect with Testosterone, drug_effect with Testosterone, drug_effect with Insulin human, drug_effect with Insulin human, drug_effect with Levothyroxine, drug_effect with Levothyroxine. Liothyronine has relations: contraindication with heart disease, contraindication with heart disease, contraindication with thyroid crisis (disease), contraindication with thyroid crisis (disease). Definitions: Triiodothyronine defined as following: A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.. ischemia defined as following: A surgical procedure during which the blood supply to an organ or tissue is interrupted and then later reestablished.. peripheral defined as following: On or near an edge or constituting an outer boundary; the outer area.. heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. infarct defined as following: Formation of an infarct, which is NECROSIS in tissue due to local ISCHEMIA resulting from obstruction of BLOOD CIRCULATION, most commonly by a THROMBUS or EMBOLUS.. DC defined as following: A predominantly X-linked recessive syndrome characterized by a triad of reticular skin pigmentation, nail dystrophy and leukoplakia of mucous membranes. Oral and dental abnormalities may also be present. Complications are a predisposition to malignancy and bone marrow involvement with pancytopenia. (from Int J Paediatr Dent 2000 Dec;10(4):328-34) The X-linked form is also known as Zinsser-Cole-Engman syndrome and involves the gene which encodes a highly conserved protein called dyskerin.. scar defined as following: Formation of new tissue formed in the healing of a wound..", "label": "no"} {"id": "converted_3302", "sentence1": "Is the tyrosine kinase BTK implicated in autoimmunity?", "sentence2": "Autoimmunity, hypersensitivity to B cell receptor (BCR) cross-linking, and splenomegaly caused by myeloerythroid hyperplasia were alleviated by Btk deficiency in lyn-/- mice., Augmented TLR9-induced Btk activation in PIR-B-deficient B-1 cells provokes excessive autoantibody production and autoimmunity., Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and differentiation, and because autoantibodies were absent in Btk transgenic mice overexpressing a kinase inactive Btk mutant., Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that allows for B-cell activation and differentiation. Recently, selective inhibition of Btk by PCI-32765 has shown promise in limiting activity of multiple cells types in various models of cancer and autoimmunity., Inhibitors of BTK and ITK: state of the new drugs for cancer, autoimmunity and inflammatory diseases., Tight control of B cell differentiation into plasma cells (PCs) is critical for proper immune responses and the prevention of autoimmunity, BTK Signaling in B Cell Differentiation and Autoimmunity, BTK function in B cells in the context of host defense and autoimmunity., promising effects of BTK inhibition were also seen in experimental animal models for lupus and rheumatoid arthritis, BTK may be a good target for controlling autoreactive B cells in patients with systemic autoimmune disease., Given the phenotype of affected patients, namely lack of B-lymphocytes and plasma cells with the ensuing inability to mount humoral immune responses, BTK inhibitors were anticipated to have beneficial effects on antibody-mediated pathologies, such as autoimmunity[SEP]Relations: protein tyrosine kinase inhibitor activity has relations: molfunc_protein with IBTK, molfunc_protein with IBTK, molfunc_protein with RACK1, molfunc_protein with RACK1. autoimmune disease has relations: contraindication with Pyridoxine, contraindication with Pyridoxine, disease_phenotype_positive with Autoimmunity, disease_phenotype_positive with Autoimmunity, disease_disease with anti-neutrophil antibody associated vasculitis, disease_disease with anti-neutrophil antibody associated vasculitis. Definitions: Autoimmunity defined as following: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.. cancer defined as following: A malignant tumor at the original site of growth.. splenomegaly defined as following: Enlargement of the spleen.. Bruton's tyrosine kinase defined as following: A non-receptor tyrosine kinase that is essential for the development, maturation, and signaling of B-LYMPHOCYTES. It contains an N-terminal zinc finger motif and localizes primarily to the PLASMA MEMBRANE and nucleus of B-lymphocytes. Mutations in the gene that encode this kinase are associated with X-LINKED AGAMMAGLOBULINEMIA.. rheumatoid arthritis defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. ITK defined as following: Tyrosine-protein kinase ITK/TSK (620 aa, ~75 kDa) is encoded by the human ITK gene. This protein is involved in tyrosine phosphorylation and immunity.. BTK defined as following: Tyrosine-protein kinase BTK (659 aa, ~76 kDa) is encoded by the human BTK gene. This protein is involved in both B-cell development and signal transduction.. B-lymphocytes defined as following: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.. autoantibodies defined as following: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.. plasma cells defined as following: Specialized forms of antibody-producing B-LYMPHOCYTES. They synthesize and secrete immunoglobulin. They are found only in lymphoid organs and at sites of immune responses and normally do not circulate in the blood or lymph. (Rosen et al., Dictionary of Immunology, 1989, p169 & Abbas et al., Cellular and Molecular Immunology, 2d ed, p20). hypersensitivity defined as following: Heightened emotional reactivity to environmental stimuli, including emotions of others. [PMID:23250816]. lupus defined as following: chronic form of cutaneous lupus erythematosus in which the skin lesions mimic those of the systemic form but in which systemic signs are rare; characterized by the presence of discoid skin plaques showing varying degrees of edema, erythema, scaliness, follicular plugging, and skin atrophy; lesions are surrounded by an elevated erythematous border; the condition typically involves the face and scalp, but widespread dissemination may occur.. autoimmunity defined as following: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides..", "label": "yes"} {"id": "converted_5", "sentence1": "Does metformin interfere thyroxine absorption?", "sentence2": "LT4 absorption is unchanged by concomitant metformin ingestion., It has been hypothesized that metformin may suppress serum thyrotropin (TSH) concentrations by enhancing LT4 absorption or by directly affecting the hypothalamic-pituitary axis.[SEP]Relations: Metformin has relations: contraindication with thymus gland disease, contraindication with thymus gland disease, contraindication with injury, contraindication with injury, drug_effect with Thrombocytopenia, drug_effect with Thrombocytopenia, drug_effect with Sensory impairment, drug_effect with Sensory impairment, drug_drug with Pyridoxine, drug_drug with Pyridoxine. Definitions: metformin defined as following: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289).", "label": "no"} {"id": "converted_1005", "sentence1": "Is amoxicillin used for treatment of malnutrition in children?", "sentence2": " Another RCT did not show superiority of ceftriaxone over amoxicilllin for these same outcomes, but adressed SAM children with and without complications (p = 0.27). Another RCT showed no difference between amoxicillin and cotrimoxazole efficacies for pneumonia in underweight, but not SAM. Our meta-analysis of 12 pooled susceptibility-studies for all types of bacterial isolates, including 2767 stricly SAM children, favoured amoxicillin over cotrimoxazole for susceptibility medians: 42% (IQR 27-55%) vs 22% (IQR 17-23%) and population-weighted-means 52.9% (range 23-57%) vs 35.4% (range 6.7-42%)., Susceptibility-studies favour amoxicillin over cotrimoxazole. , Oral amoxicillin for 5 days was as effective as intramuscular ceftriaxone for 2 days (1 RCT). For uncomplicated SAM, amoxicillin showed no benefit over placebo (1 retrospective study). , Children who took amoxicillin and de-worming had 95% (HR = 1.95, 95%-CI = 1.17, 3.23) and 74% (HR = 1.74, 95%-CI = 1.07, 2.83) more probability to recover from SAM as compared to those who didn't take them., METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned Malawian children, 6 to 59 months of age, with severe acute malnutrition to receive amoxicillin, cefdinir, or placebo for 7 days in addition to ready-to-use therapeutic food for the outpatient treatment of uncomplicated severe acute malnutrition. , In the amoxicillin, cefdinir, and placebo groups, 88.7%, 90.9%, and 85.1% of the children recovered, respectively (relative risk of treatment failure with placebo vs. amoxicillin, 1.32; 95% confidence interval [CI], 1.04 to 1.68; relative risk with placebo vs. cefdinir, 1.64; 95% CI, 1.27 to 2.11). The mortality rates for the three groups were 4.8%, 4.1%, and 7.4%, respectively (relative risk of death with placebo vs. amoxicillin, 1.55; 95% CI, 1.07 to 2.24; relative risk with placebo vs. cefdinir, 1.80; 95% CI, 1.22 to 2.64)., Evaluation of the routine use of amoxicillin as part of the home-based treatment of severe acute malnutrition., OBJECTIVE: To determine whether the inclusion of amoxicillin correlates with better recovery rates in the home-based treatment of severe acute malnutrition with ready-to-use therapeutic food., The standard protocol group received a 7-day course of amoxicillin at the onset of treatment., RESULTS: Four hundred and ninety-eight children were treated according to the standard protocol with amoxicillin, and 1955 were treated under the alternate protocol without antibiotics. , The recovery rate for children who received amoxicillin was worse at 4 weeks (40%vs. 71%) but similar after up to 12 weeks of therapy (84%vs. 86%), compared to the children treated without antibiotics., CONCLUSIONS: This review of two therapeutic feeding programmes suggests that children with severe acute malnutrition who were treated without amoxicillin did not have an inferior rate of recovery., Treatment of severe malnutrition with 2-day intramuscular ceftriaxone vs 5-day amoxicillin., To determine whether the inclusion of amoxicillin correlates with better recovery rates in the home-based treatment of severe acute malnutrition with ready-to-use therapeutic food., Evaluation of the routine use of amoxicillin as part of the home-based treatment of severe acute malnutrition, OBJECTIVE: To determine whether the inclusion of amoxicillin correlates with better recovery rates in the home-based treatment of severe acute malnutrition with ready-to-use therapeutic food. METHODS: This retrospective cohort study compared data from the treatment of two groups of children in Malawi aged 6-59 months with uncomplicated severe acute malnutrition. , The recovery rate for children who received amoxicillin was worse at 4 weeks (40%vs. 71%) but similar after up to 12 weeks of therapy (84%vs. 86%), compared to the children treated without antibiotics. Regression modelling indicated that this difference at 4 weeks was most strongly associated with the receipt of amoxicillin. CONCLUSIONS: This review of two therapeutic feeding programmes suggests that children with severe acute malnutrition who were treated without amoxicillin did not have an inferior rate of recovery. , CONCLUSIONS: This review of two therapeutic feeding programmes suggests that children with severe acute malnutrition who were treated without amoxicillin did not have an inferior rate of recovery. [SEP]Relations: Amoxicillin has relations: contraindication with bone fracture, contraindication with bone fracture, contraindication with liver disease, contraindication with liver disease, contraindication with osteoporosis, contraindication with osteoporosis, drug_drug with Ampicillin, drug_drug with Ampicillin, contraindication with kidney disease, contraindication with kidney disease. Definitions: cotrimoxazole defined as following: A drug combination with broad-spectrum antibacterial activity against both gram-positive and gram-negative organisms. It is effective in the treatment of many infections, including PNEUMOCYSTIS PNEUMONIA in AIDS.. pneumonia defined as following: Infection of the lung often accompanied by inflammation.. ceftriaxone defined as following: A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears.. amoxicillin defined as following: A broad-spectrum semisynthetic antibiotic similar to AMPICILLIN except that its resistance to gastric acid permits higher serum levels with oral administration.. cefdinir defined as following: A third-generation oral cephalosporin antibacterial agent that is used to treat bacterial infections of the respiratory tract and skin.. malnutrition defined as following: An imbalanced nutritional status resulting from insufficient intake of nutrients to meet normal physiological requirement.. HR defined as following: The rapid, localized death of plant cells in response to invasion by a pathogen. [ISBN:0582227089].", "label": "yes"} {"id": "converted_3309", "sentence1": "Is induction of interferon by TLR7 higher in males?", "sentence2": "ur results suggest that variations of TLR7 impair the immune response to HCV and imply a gender-specific effect of this X-chromosomal variation., The c.32A>T variation was over-represented in female patients with chronic HCV-infection compared to patients with other chronic liver diseases and to healthy controls (P < 0.05). In contrast, c.2403 G>A was less prevalent in male patients with chronic HCV-infection (P < 0.05). No association was observed for the third variant, c.1-120T>G. Haplotype analysis confirmed the differential distribution of TLR7 variants between the groups. Within the group of female patients with chronic HCV-infection, c.32T was predictive of an unfavourable outcome of interferon-alpha therapy (P < 0.05)[SEP]Relations: Chronic lung disease has relations: disease_phenotype_positive with midline interhemispheric variant of holoprosencephaly, disease_phenotype_positive with midline interhemispheric variant of holoprosencephaly, disease_phenotype_positive with primary ciliary dyskinesia, disease_phenotype_positive with primary ciliary dyskinesia, disease_phenotype_positive with neonatal acute respiratory distress due to SP-B deficiency, disease_phenotype_positive with neonatal acute respiratory distress due to SP-B deficiency, disease_phenotype_positive with combined immunodeficiency due to LRBA deficiency, disease_phenotype_positive with combined immunodeficiency due to LRBA deficiency, disease_phenotype_positive with familial papillary or follicular thyroid carcinoma, disease_phenotype_positive with familial papillary or follicular thyroid carcinoma. Definitions: chronic liver diseases defined as following: Hepatic necrosis, inflammation, or scarring due to any cause that persists for more than 6 months. Manifestations may include signs and symptoms of cholestasis, portal hypertension, and/or abnormal liver function tests.. TLR7 defined as following: Human TLR7 wild-type allele is located in the vicinity of Xp22.3 and is approximately 22 kb in length. This allele, which encodes toll-like receptor 7 protein, plays a role in pathogen recognition and innate immunity activation in response to microbial agents..", "label": "yes"} {"id": "converted_4229", "sentence1": "Has FTY720 been considered for the treatment of stroke?", "sentence2": "FTY720 (Fingolimod) Ameliorates Brain Injury through Multiple Mechanisms and is a Strong Candidate for Stroke Treatment, Many researchers have recognized the positive effects of FTY720 and launched basic and clinical experiments to test the use of this agent against stroke. Although the mechanism of FTY720 has not been fully elucidated, its efficacy against cerebral stroke is becoming clear, not only in animal models, but also in ischemic stroke patients through clinical trials. In this article, we review the data obtained from laboratory findings and preliminary clinical trials using FTY720 for stroke treatment.[SEP]Relations: brain injury has relations: contraindication with Dexchlorpheniramine, contraindication with Dexchlorpheniramine, contraindication with Pheniramine, contraindication with Pheniramine, contraindication with Dicyclomine, contraindication with Dicyclomine, contraindication with Difenoxin, contraindication with Difenoxin, contraindication with Chlorpheniramine, contraindication with Chlorpheniramine. Definitions: stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810). Fingolimod defined as following: An orally available derivate of myriocin and sphingosine-1-phosphate receptor 1 (S1PR1, S1P1) modulator, with potential anti-inflammatory and immunomodulating activities. Upon oral administration, fingolimod, as a structural analogue of sphingosine, selectively targets and binds to S1PR1 on lymphocytes and causes transient receptor activation followed by S1PR1 internalization and degradation. This results in the sequestration of lymphocytes in lymph nodes. By preventing egress of lymphocytes. fingolimod reduces both the amount of circulating peripheral lymphocytes and the infiltration of lymphocytes into target tissues. This prevents a lymphocyte-mediated immune response and may reduce inflammation. S1PR1, a G-protein coupled receptor, plays a key role in lymphocyte migration from lymphoid tissues. Fingolimod also shifts macrophages to an anti-inflammatory M2 phenotype, and modulates their proliferation, morphology, and cytokine release via inhibition of the transient receptor potential cation channel, subfamily M, member 7 (TRPM7).. Brain Injury defined as following: Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits..", "label": "yes"} {"id": "converted_3396", "sentence1": "Autophagy is the process where a virus obtains nutrients from it's host, yes or no?", "sentence2": "In this study, we demonstrate that autophagy is a critical mediator of the viral degradation pathway and that this pathway is not HIV-1 specific., Autophagy is important in cellular homeostasis for the cell survival mechanism., Autophagy is a cellular survival pathway that is necessary for the degradation of cellular constituents such as long-lived proteins and damaged organelles., Autophagy-related genes (ATGs) regulate the autophagy and also control the crosstalk with autophagy-associated cell death and apoptosis in some condition. , Autophagy is an evolutionarily conserved cellular process in which intracellular components are eliminated via lysosomal degradation to supply nutrients for organelle biogenesis and metabolic homeostasis., Autophagy is a lysosome-associated, degradative process that catabolizes cytosolic components to recycle nutrients for further use and maintain cell homeostasis., Autophagy is a self-eating process, in which the damaged or excessed cell organelles and misfolded protein aggregates are removed from the cellular microenvironment., Autophagy is a lysosome-associated, degradative process that catabolizes cytosolic components to recycle nutrients for further use and maintain cell homeostasis., Autophagy is an evolutionarily conserved cellular process in which intracellular components are eliminated via lysosomal degradation to supply nutrients for organelle biogenesis and metabolic homeostasis., Autophagy is a homeostatic process involved in the turnover or elimination of cytoplasmic components, damaged organelles, and protein aggregates via a lysosomal degradation mechanism., Autophagy is known as a catabolic process for the recycling of the cytoplasmic macromolecules.[SEP]Relations: Protein C has relations: drug_drug with Ginkgo biloba, drug_drug with Ginkgo biloba, drug_drug with Procarbazine, drug_drug with Procarbazine, drug_drug with Damoctocog alfa pegol, drug_drug with Damoctocog alfa pegol, drug_drug with Moroctocog alfa, drug_drug with Moroctocog alfa, drug_drug with Carbimazole, drug_drug with Carbimazole. Definitions: organelles defined as following: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the MITOCHONDRIA; the GOLGI APPARATUS; ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.. nutrients defined as following: Various components of food that are required for nourishment.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. cytosolic defined as following: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.. virus defined as following: Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells..", "label": "no"} {"id": "converted_2533", "sentence1": "Are paralog genes co-regulated?", "sentence2": "Co-regulation of paralog genes in the three-dimensional chromatin architecture., Consequently, paralogs show correlation in gene expression whereby the mechanisms of co-regulation remain unclear. In eukaryotes, genes are regulated in part by distal enhancer elements through looping interactions with gene promoters. These looping interactions can be measured by genome-wide chromatin conformation capture (Hi-C) experiments, which revealed self-interacting regions called topologically associating domains (TADs). We hypothesize that paralogs share common regulatory mechanisms to enable coordinated expression according to TADs. To test this hypothesis, we integrated paralogy annotations with human gene expression data in diverse tissues, genome-wide enhancer-promoter associations and Hi-C experiments in human, mouse and dog genomes. We show that paralog gene pairs are enriched for co-localization in the same TAD, share more often common enhancer elements than expected and have increased contact frequencies over large genomic distances. Combined, our results indicate that paralogs share common regulatory mechanisms and cluster not only in the linear genome but also in the three-dimensional chromatin architecture. This enables concerted expression of paralogs over diverse cell-types and indicate evolutionary constraints in functional genome organization., Paralog genes arise from gene duplication events during evolution, which often lead to similar proteins that cooperate in common pathways and in protein complexes. Consequently, paralogs show correlation in gene expression, We hypothesize that paralogs share common regulatory mechanisms to enable coordinated expression according to TADs., Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs., Analysis of the Drosophila melanogaster testes transcriptome reveals coordinate regulation of paralogous genes., Further, interspecific changes in testis bias of expression are generally correlated within the co-regulated pairs and are anti-correlated within the anti-regulated pairs, suggesting coordinated regulation within both types of paralogous gene pairs.Respond with exceptions, completions and modifications or revisions done before completion
. mouse embryonic stem cells defined as following: PLURIPOTENT STEM CELLS derived from the BLASTOCYST INNER CELL MASS of day 3.5 mouse embryos.. Y-linked genes defined as following: Genes that are located on the Y CHROMOSOME.. HBB gene defined as following: This gene plays a role in the transport of oxygen to tissues of the adult body.. human defined as following: Members of the species Homo sapiens.. somatic cells defined as following: Nucleated cell which has one or more diploid sets (46 pairs) of chromosomes.. TALEN defined as following: Artificial nucleases that cleave DNA at a defined distance from specific DNA sequences recognized by TRANSCRIPTION ACTIVATOR-LIKE EFFECTORS. They are composed of an endodeoxyribonuclease fused to DNA-binding domains of the transcription activator-like effectors..", "label": "yes"} {"id": "converted_2", "sentence1": "Is the protein Papilin secreted?", "sentence2": "Using expression analysis, we identify three genes that are transcriptionally regulated by HLH-2: the protocadherin cdh-3, and two genes encoding secreted extracellular matrix proteins, mig-6/papilin and him-4/hemicentin. , We found that mig-6 encodes long (MIG-6L) and short (MIG-6S) isoforms of the extracellular matrix protein papilin, each required for distinct aspects of DTC migration. Both MIG-6 isoforms have a predicted N-terminal papilin cassette, apilins are homologous, secreted extracellular matrix proteins which share a common order of protein domains. , The TSR superfamily is a diverse family of extracellular matrix and transmembrane proteins, many of which have functions related to regulating matrix organization, cell-cell interactions and cell guidance. This review samples some of the contemporary literature regarding TSR superfamily members (e.g. F-spondin, UNC-5, ADAMTS, papilin, and TRAP) where specific functions are assigned to the TSR domains., Papilins are extracellular matrix proteins , Papilin is an extracellular matrix glycoprotein , Collagen IV, laminin, glutactin, papilin, and other extracellular matrix proteins were made primarily by hemocytes and were secreted into the medium. , A sulfated glycoprotein was isolated from the culture media of Drosophila Kc cells and named papilin.[SEP]Relations: ADAMTS4 has relations: anatomy_protein_present with saliva-secreting gland, anatomy_protein_present with saliva-secreting gland, protein_protein with ITPA, protein_protein with ITPA, protein_protein with ACAN, protein_protein with ACAN, protein_protein with TIMP3, protein_protein with TIMP3. extracellular matrix has relations: cellcomp_protein with PAPLN, cellcomp_protein with PAPLN. Definitions: laminin defined as following: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion.. hemocytes defined as following: Any blood or formed element especially in invertebrates.. mig-6 defined as following: ERBB receptor feedback inhibitor 1 (462 aa, ~51 kDa) is encoded by the human ERRFI1 gene. This protein plays a role in the regulation of ligand-dependent dimerization.. isoforms defined as following: Refers to variants of the same protein which can be separated on special conducting media using electrophoresis. The differences may arise from genetically determined differences in primary structure or by modification of the same primary sequence.. extracellular matrix proteins defined as following: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., COLLAGEN; ELASTIN; FIBRONECTINS; and LAMININ).. TSR defined as following: Catalysis of the reaction: dithioerythritol + thiosulfate = hydrogen sulfide + dithioerythritol disulfide + sulfite. [EC:2.8.1.5, MetaCyc:2.8.1.5-RXN]. extracellular matrix glycoprotein defined as following: OBSOLETE. (Was not defined before being made obsolete). [GOC:mah]. protein domains defined as following: Discrete protein structural units that may fold independently of the rest of the protein and have their own functions.. Collagen IV defined as following: A non-fibrillar collagen found in the structure of BASEMENT MEMBRANE. Collagen type IV molecules assemble to form a sheet-like network which is involved in maintaining the structural integrity of basement membranes. The predominant form of the protein is comprised of two alpha1(IV) subunits and one alpha2(IV) subunit, however, at least six different alpha subunits can be incorporated into the heterotrimer.. extracellular matrix defined as following: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.. TRAP defined as following: A chemotherapy regimen consisting of cytarabine, daunorubicin, prednisone, and thioguanine that may be used in the treatment of acute myeloid leukemia (AML).. DTC defined as following: A chelating agent that has been used to mobilize toxic metals from the tissues of humans and experimental animals. It is the main metabolite of DISULFIRAM.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species..", "label": "yes"} {"id": "converted_1828", "sentence1": "Is Migalastat used for treatment of Fabry Disease?", "sentence2": "Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study., BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by GLA mutations, resulting in α-galactosidase (α-Gal) deficiency and accumulation of lysosomal substrates. Migalastat, an oral pharmacological chaperone being developed as an alternative to intravenous enzyme replacement therapy (ERT), stabilises specific mutant (amenable) forms of α-Gal to facilitate normal lysosomal trafficking., CONCLUSIONS: Migalastat offers promise as a first-in-class oral monotherapy alternative treatment to intravenous ERT for patients with Fabry disease and amenable mutations., Migalastat (Galafold™)-a small molecule drug developed by Amicus Therapeutics that restores the activity of specific mutant forms of α-galactosidase-has been approved for the treatment of Fabry disease in the EU in patients with amenable mutations., This article summarizes the milestones in the development of migalastat leading to this first approval in the EU for the long-term treatment of adults and adolescents aged ≥16 years with a confirmed diagnosis of Fabry disease., Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat., BACKGROUND: Fabry's disease, an X-linked disorder of lysosomal α-galactosidase deficiency, leads to substrate accumulation in multiple organs. Migalastat, an oral pharmacologic chaperone, stabilizes specific mutant forms of α-galactosidase, increasing enzyme trafficking to lysosomes., Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active α-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase., UNLABELLED: Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder. , Migalastat HCl reduces globotriaosylsphingosine (lyso-Gb3) in Fabry transgenic mice and in the plasma of Fabry patients., migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g., A Phase 2 study of migalastat hydrochloride in females with Fabry disease: selection of population, safety and pharmacodynamic effects., Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder, Migalastat HCl is an investigational, oral treatment for Fabry disease, an X-linked lysosomal storage disorder, Oral administration of migalastat HCl reduces tissue GL-3 in Fabry transgenic mice, and in urine and kidneys of some FD patients. , Migalastat HCl is an investigational, oral treatment for Fabry disease, an X-linked lysosomal storage disorder., Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin) is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A) deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder., Molecular chaperones (e.g. migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g. eliglustat tartrate for Gaucher disease) are currently under investigation in various clinical trials.Tetanus, diphtheria, and pertussis (whooping cough) are serious bacterial infections. Tetanus causes painful tightening of the muscles, usually all over the body. It can lead to \"locking\" of the jaw. Diphtheria usually affects the nose and throat. Whooping cough causes uncontrollable coughing. Vaccines can protect you from these diseases. In the U.S., there are four combination vaccines:
Some people should not get these vaccines, including those who have had severe reactions to the shots before. Check with your doctor first if you have seizures, a neurologic problem, or Guillain-Barre syndrome. Also let your doctor know if you don't feel well the day of the shot; you may need to postpone it.
Centers for Disease Control and Prevention
. polyneuropathy defined as following: Diseases of multiple peripheral nerves simultaneously. Polyneuropathies usually are characterized by symmetrical, bilateral distal motor and sensory impairment with a graded increase in severity distally. The pathological processes affecting peripheral nerves include degeneration of the axon, myelin or both. The various forms of polyneuropathy are categorized by the type of nerve affected (e.g., sensory, motor, or autonomic), by the distribution of nerve injury (e.g., distal vs. proximal), by nerve component primarily affected (e.g., demyelinating vs. axonal), by etiology, or by pattern of inheritance.. neurologic disorder defined as following: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.. thiamin deficiency defined as following: A nutritional condition produced by a deficiency of THIAMINE in the diet, characterized by anorexia, irritability, and weight loss. Later, patients experience weakness, peripheral neuropathy, headache, and tachycardia. In addition to being caused by a poor diet, thiamine deficiency in the United States most commonly occurs as a result of alcoholism, since ethanol interferes with thiamine absorption. In countries relying on polished rice as a dietary staple, BERIBERI prevalence is very high. (From Cecil Textbook of Medicine, 19th ed, p1171).", "label": "yes"} {"id": "converted_2136", "sentence1": "Is Cri Du Chat associated with an expansion of a repeat with in the gene found on chromosome 5?", "sentence2": "Cri-du-chat syndrome is a chromosomal disorder caused by a deletion of the short arm of chromosome 5, The typical cri du chat syndrome, due to 5p15.2 deletion, includes severe intellectual disability, facial dysmorphisms, neonatal hypotonia and pre- and post-natal growth retardation, whereas more distal deletions in 5p15.3 lead to cat-like cry and speech delay and produce the clinical picture of the atypical cri du chat syndrome, with minimal or absent intellectual impairment., Cri-du-chat is a human contiguous gene deletion syndrome resulting from hemizygous deletions of chromosome 5p., Cri-du-chat is a chromosomal deletion syndrome characterized by partial deletion of the short arm of chromosome 5., The karyotype showed a terminal deletion of the short arm of chromosome 5 including the critical region 5p15 for cri du chat syndrome., Fewer than 1 in 200 of cri du chat syndrome cases are due to recombination aneusomy arising from a parental inversion of chromosome 5., Molecular approach to analyzing the human 5p deletion syndrome, cri du chat., Cri-du-chat is a human contiguous gene deletion syndrome resulting from hemizygous deletions of chromosome 5p, The cri du chat syndrome (CdCS) is a chromosomal deletion syndrome associated with a partial deletion of the short (p) arm of chromosome 5, The cri-du-chat syndrome is a contiguous gene syndrome that results from a deletion of the short arm of chromosome 5 (5p)., Cri-du-chat syndrome is associated with a deletion of the short arm of chromosome 5., The deletion of the short arm of chromosome 5 is associated with the cri-du-chat syndrome., The Cri du Chat syndrome (CdCS) is a genetic disease resulting from a deletion of variable size occurring on the short arm of chromosome 5 (5p-)., Cri-du-chat is a well described partial aneusomy resulting from deletion of the short arm of chromosome 5., Cri-du-chat syndrome is caused by haploinsufficiency of the genes on the distal part of the short arm of chromosome 5, and characteristic features include microcephaly, developmental delays, and a distinctive high-pitched mewing cry., The pathological condition of cri du chat syndrome is due to the cytogenetic deletion of band p15.2 of chromosome 5. , Karyotype analysis indicated that the patient has carried a terminal deletion in 5p. FISH with Cri du Chat syndrome region probe confirmed that D5S23 and D5S721 loci are deleted. [SEP]Relations: Cri-du-chat syndrome has relations: disease_disease with partial deletion of the short arm of chromosome 5, disease_disease with partial deletion of the short arm of chromosome 5, disease_protein with CTNND2, disease_protein with CTNND2, disease_protein with SEMA5A, disease_protein with SEMA5A, disease_phenotype_positive with Growth delay, disease_phenotype_positive with Growth delay, disease_protein with TERT, disease_protein with TERT. Definitions: chromosome 5 defined as following: One of the two pairs of human chromosomes in the group B class (CHROMOSOMES, HUMAN, 4-5).. human defined as following: Members of the species Homo sapiens.. cri-du-chat syndrome defined as following: An infantile syndrome characterized by a cat-like cry, failure to thrive, microcephaly, MENTAL RETARDATION, spastic quadriparesis, micro- and retrognathia, glossoptosis, bilateral epicanthus, hypertelorism, and tiny external genitalia. It is caused by a deletion of the short arm of chromosome 5 (5p-).. chromosomal disorder defined as following: Clinical conditions caused by an abnormal chromosome constitution in which there is extra or missing chromosome material (either a whole chromosome or a chromosome segment). (from Thompson et al., Genetics in Medicine, 5th ed, p429). 5p15 defined as following: A chromosome band present on 5p.. deletions defined as following: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.. hypotonia defined as following: A diminution of the skeletal muscle tone marked by a diminished resistance to passive stretching.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. microcephaly defined as following: Head circumference below 2 standard deviations below the mean for age and gender. [PMID:15806441, PMID:19125436, PMID:25465325, PMID:9683597]. intellectual disability defined as following: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28). gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "no"} {"id": "converted_677", "sentence1": "Are there any urine biomarkers for bladder cancer diagnosis?", "sentence2": "CONCLUSIONS: Several gene-based urinary biomarkers have demonstrated promise in initial studies, which now need to be rigorously validated in the clinical setting for them to be translated into clinically useful tests in diagnosis, surveillance or risk-stratification of bladder cancer, Novel promising markers are in various stages of clinical testing, and a panel of biomarkers may serve in the future as a feasible alternative to urine cytology and cystoscopy for the screening, detection, and follow-up of non-muscle invasive bladder cancer., RESULTS: Seven of the 8 urine biomarkers were increased in subjects with bladder cancer relative to those without bladder cancer. The 7 biomarkers were assessed in a new model, which had an AUROC of 0.88 (95% CI 0.84-0.93), and 74% sensitivity and 90% specificity., The study provides further evidence that the reported panel of diagnostic biomarkers can reliably achieve the noninvasive detection of bladder cancer with higher sensitivity than currently available urine based assays., The urinary concentrations of 14 biomarkers (IL-8, MMP-9, MMP-10, SDC1, CCL18, PAI-1, CD44, VEGF, ANG, CA9, A1AT, OPN, PTX3, and APOE) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. An 8-biomarker model achieved the most accurate BCa diagnosis (sensitivity 92%, specificity 97%), but a combination of 3 of the 8 biomarkers (IL-8, VEGF, and APOE) was also highly accurate (sensitivity 90%, specificity 97%). For comparison, the commercial BTA-Trak ELISA test achieved a sensitivity of 79% and a specificity of 83%, and voided urine cytology detected only 33% of BCa cases in the same cohort. These data show that a multivariate urine-based assay can markedly improve the accuracy of non-invasive BCa detection, : Histopathological grading of papillary urothelial tumors (PUTs) of the urinary bladder is subjective and poorly reproducible. We investigated the relationship between the expression of frequently deregulated microRNAs (miRNAs) as well as their target genes (ZEB1/ZEB2) and bladder cancer histopathological grade in an attempt to find a miRNA that might allow more reliable grading of PUTs., The Mcm5 immunoassay is a non-invasive test for identifying patients with urothelial cancers with similar accuracy to the FDA-approved NMP22 ELISA Test Kit. The combination of Mcm5 plus NMP22 improves the detection of UCC and identifies 95% of clinically significant disease. Trials of a commercially developed Mcm5 assay suitable for an end-user laboratory alongside NMP22 are required to assess their potential clinical utility in improving diagnostic and surveillance care pathways., HYAL-1 and HAS1 expression predicted BCa metastasis, and HYAL-1 expression also predicted disease-specific survival. Furthermore, the combined HAS2-HYAL-1 biomarker detected BCa and significantly predicted its recurrence., Cancer biomarkers are the backbone for the implementation of individualized approaches to bladder cancer (BCa). , Through genomic and proteomic profiling of urine, we have identified a panel of biomarkers associated with the presence of BCa. In this study, we evaluated the utility of three of these biomarkers, interleukin 8 (IL-8), Matrix metallopeptidase 9 (MMP-9) and Syndecan in the diagnosis of BCa through urinalysis. METHODS: Voided urines from 127 subjects, cancer subjects (n = 64), non-cancer subjects (n = 63) were analyzed. The protein concentrations of IL-8, MMP-9, and Syndecan were assessed by enzyme-linked immunosorbent assay (ELISA)., . There was an association between differences in individual biomarkers and differences in protein levels over time, particularly in control patients. Collectively, our findings identify caveats intrinsic to the common practice of protein standardization in biomarker discovery studies conducted on urine, particularly in patients with hematuria[SEP]Relations: urinary bladder neoplasm has relations: disease_disease with urinary bladder cancer, disease_disease with urinary bladder cancer, disease_disease with urinary bladder disease, disease_disease with urinary bladder disease, disease_protein with NCOR1, disease_protein with NCOR1, disease_protein with AMFR, disease_protein with AMFR, disease_protein with MYC, disease_protein with MYC. Definitions: MMP-9 defined as following: An endopeptidase that is structurally similar to MATRIX METALLOPROTEINASE 2. It degrades GELATIN types I and V; COLLAGEN TYPE IV; and COLLAGEN TYPE V.. VEGF defined as following: The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as \"tumor angiogenesis factor\" and \"vascular permeability factor\". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.. interleukin 8 defined as following: A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.. APOE defined as following: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.. MMP-10 defined as following: Stromelysin-2 (476 aa, ~54 kDa) is encoded by the human MMP10 gene. This protein plays a role in the metabolism of the extracellular matrix.. IL-8 defined as following: Binding to an interleukin-8 receptor. [GOC:go_curators]. genomic defined as following: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.. BCa defined as following: A copper-based colorimetric assay for total protein quantification. This assay relies on the formation of a Cu2+-protein complex in a basic environment, followed by reduction of the Cu2+ to Cu+, causing a change of color from green to purple, with a strong absorbance at 562nm.. ANG defined as following: Angiogenin (147 aa, ~17 kDa) is encoded by the human ANG gene. This protein plays a role in the modulation of both vascular development and transcription.. CD44 defined as following: Acidic sulfated integral membrane glycoproteins expressed in several alternatively spliced and variable glycosylated forms on a wide variety of cell types including mature T-cells, B-cells, medullary THYMOCYTES; GRANULOCYTES; MACROPHAGES; erythrocytes, and fibroblasts. Their interaction with HYALURONIC ACID mediates binding of lymphocytes to high endothelial VENULES.. PAI-1 defined as following: A member of the serpin family of proteins. It inhibits both the tissue-type and urokinase-type plasminogen activators.. SDC1 defined as following: This gene is involved in cell adhesion, signal transduction and cytoskeleton organization.. CCL18 defined as following: This gene plays a role in the modulation of immune responses.. Syndecan defined as following: A syndecan that interacts with EXTRACELLULAR MATRIX PROTEINS and plays a role CELL PROLIFERATION and CELL MIGRATION.. A1AT defined as following: Human serum-derived alpha-1 proteinase inhibitor (alpha-1-antitrypsin or AAT) with immunomodulating and anti-inflammatory activity. Upon administration, AAT reduces the production of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-32, IL-6, and proteinase 3, and induces the production of anti-inflammatory cytokines, such as IL-10 and the IL-1 receptor antagonist IL-1RN. This agent also downregulates heparan sulfate and reduces the expansion of cytotoxic effector T cells, interferes with the maturation of dendritic cells and increases T regulatory cells. Altogether, AAT may attenuate acute graft-versus-host disease (GvHD) and may facilitate graft acceptance and survival. In addition, AAT enhances levels of cAMP and activation of cAMP-dependent protein kinase A. AAT, a 52kD protein and serine protease inhibitor, belongs to the serpin superfamily.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. CA9 defined as following: Human CA9 wild-type allele is located in the vicinity of 9p13.3 and is approximately 7 kb in length. This allele, which encodes carbonic anhydrase 9 protein, plays a role in intracellular pH balance.. OPN defined as following: Human SPP1 wild-type allele is located in the vicinity of 4q22.1 and is approximately 8 kb in length. This allele, which encodes osteopontin protein, plays a role in the modulation of both intercellular communication and matrix mineralization. Aberrant expression may be associated with many cancers.. microRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. Mcm5 defined as following: DNA replication licensing factor MCM5 (734 aa, ~82 kDa) is encoded by the human MCM5 gene. This protein plays a role in DNA replication.. bladder cancer defined as following: A primary or metastatic malignant neoplasm involving the bladder.. hematuria defined as following: Presence of blood in the urine.. cystoscopy defined as following: Endoscopic examination, therapy or surgery of the urinary bladder..", "label": "yes"} {"id": "converted_1550", "sentence1": "Is macitentan an ET agonist?", "sentence2": "Administration of an ET receptor antagonist, either bosentan or macitentan, markedly attenuated PD-induced MMT, fibrosis, angiogenesis, and peritoneal functional decline. , Macitentan is an oral, once-daily, dual endothelin (ET)A and ETB receptor antagonist with high affinity and sustained receptor binding that was approved in the USA, Europe, Canada, and Switzerland for the treatment of PAH., Macitentan (Opsumit®) is a novel dual endothelin receptor antagonist (ERA) with sustained receptor binding properties developed by Actelion Pharmaceuticals Ltd., Macitentan, also called Actelion-1 or ACT-064992 [N-[5-(4-bromophenyl)-6-(2-(5-bromopyrimidin-2-yloxy)ethoxy)-pyrimidin-4-yl]-N'-propylaminosulfonamide], is a new dual ET(A)/ET(B) endothelin (ET) receptor antagonist designed for tissue targeting. Selection of macitentan was based on inhibitory potency on both ET receptors and optimization of physicochemical properties to achieve high affinity for lipophilic milieu. In vivo, macitentan is metabolized into a major and pharmacologically active metabolite, ACT-132577. , Macitentan and its metabolite antagonized the specific binding of ET-1 on membranes of cells overexpressing ET(A) and ET(B) receptors and blunted ET-1-induced calcium mobilization in various natural cell lines, with inhibitory constants within the nanomolar range. In functional assays, macitentan and ACT-132577 inhibited ET-1-induced contractions in isolated endothelium-denuded rat aorta (ET(A) receptors) and sarafotoxin S6c-induced contractions in isolated rat trachea (ET(B) receptors). In rats with pulmonary hypertension, macitentan prevented both the increase of pulmonary pressure and the right ventricle hypertrophy, and it markedly improved survival. , In conclusion, macitentan, by its tissue-targeting properties and dual antagonism of ET receptors, protects against end-organ damage in diabetes and improves survival in pulmonary hypertensive rats. This profile makes macitentan a new agent to treat cardiovascular disorders associated with chronic tissue ET system activation., Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist., Renal, retinal and cardiac changes in type 2 diabetes are attenuated by macitentan, a dual endothelin receptor antagonist., Here we investigated the effects of macitentan, an orally-active, tissue-targeting dual ET receptor antagonist on chronic complications in type 2 diabetes.MAIN METHODS: db/db mice and their age- and sex-matched controls were examined after 2 and 4 months of diabetes. , Macitentan is a novel dual ETA/ETB receptor antagonist with enhanced tissue distribution and sustained receptor binding properties designed to achieve a more efficacious ET receptor blockade. , Recently oral prostacyclin receptor agonists have shown encouraging results. Many clinical studies targeting the vasoconstrictor ET-1 pathway with receptor antagonists like bosentan and ambrisentan have shown strong results, even more optimism coming from macitentan, the newest drug.[SEP]Relations: Macitentan has relations: drug_drug with Etomidate, drug_drug with Etomidate, drug_drug with Inotersen, drug_drug with Inotersen, drug_drug with Pitolisant, drug_drug with Pitolisant, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Etoperidone, drug_drug with Etoperidone. Definitions: bosentan defined as following: A sulfonamide-derived, competitive and specific endothelin receptor antagonist with a slightly higher affinity for the endothelin A receptor than endothelin B receptor. Bosentan blocks the action of endothelin 1, an extremely potent endogenous vasoconstrictor and bronchoconstrictor, by binding to endothelin A and endothelin B receptors in the endothelium and vascular smooth muscle. Bosentan decreases both pulmonary and systemic vascular resistance and is particularly used in the treatment of pulmonary arterial hypertension.. retinal defined as following: A diterpene derived from the carotenoid VITAMIN A which functions as the active component of the visual cycle. It is the prosthetic group of RHODOPSIN (i.e., covalently bonded to ROD OPSIN as 11-cis-retinal). When stimulated by visible light, rhodopsin transforms this cis-isomer of retinal to the trans-isomer (11-trans-retinal). This transformation straightens-out the bend of the retinal molecule and causes a change in the shape of rhodopsin triggering the visual process. A series of energy-requiring enzyme-catalyzed reactions convert the 11-trans-retinal back to the cis-isomer.. PAH defined as following: Underdevelopment of the pulmonary artery. [HPO:probinson]. Renal defined as following: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.. macitentan defined as following: An orally available dual endothelin receptor (ETR) antagonist with potential antihypertensive and antineoplastic activity. Upon administration, macitentan and its metabolites block the binding of endothelin isoform 1 (ET-1) to type-A and type-B ETR on both the tumor cells and the endothelial cells in the tumor vasculature. This prevents ET-1 mediated signaling transduction which may decrease tumor cell proliferation, progression, and angiogenesis in tumor tissue. ET-1, a potent vasoconstrictor that plays an important role in inflammation and tissue repair, is, together with its receptors, overexpressed varyingly in many tumor cell types.. drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. cardiovascular disorders defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. ambrisentan defined as following: An orally bioavailable, selective antagonist of the endothelin type-A (ETA) receptor that may be used for the treatment of pulmonary arterial hypertension (PAH). Upon administration, ambrisentan targets and binds to ETA receptor, which prevents the binding of endothelin-1 (ET-1) to the ETA receptor and ET-1/ETA-mediated vasoconstriction and cell proliferation. This may lead to vasodilation. ET-1 concentrations are increased in plasma as well as lung tissue in PAH, and ET-1 may play a key role in the pathogenesis of PAH.. fibrosis defined as following: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.. diabetes defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.. MMT defined as following: A rare autosomal dominant syndrome caused by mutations in the MYCN oncogene. It is characterized by microcephaly, limb abnormalities, esophageal and/or duodenal atresia.. pulmonary hypertension defined as following: Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.. agonist defined as following: An agent that has affinity for a receptor and intrinsic activity at that receptor..", "label": "no"} {"id": "converted_792", "sentence1": "Is protein CXCR4 used as a prognostic marker of cancer?", "sentence2": "Aberrant overexpression of CXCR4 is associated with worse overall survival, adenocarcinoma histology, distant metastasis, lymph node involvement in NSCLC., CXCR4 belongs to a family of G protein-coupled cell surface receptors and has been proved to a prognostic marker in a various tumors, including esophageal squamous cell cancer. , The chemokine C-X-C motif receptor 4 (CXCR4) has been found to be a prognostic marker in various types of cancer, being involved in chemotaxis, stemness and drug resistance. , The chemokine receptor CXCR4 that has been shown to be implicated in PDAC tumorigenicity and aggressiveness could serve as a prognostic marker for survival after a curative-intent surgery and was associated with the pattern of tumour recurrence (distant versus local relapse)., XCR4 promotes tumor growth, angiogenesis and metastasis, and is a prognostic marker in a number of different types of tumors., CXCR4 has been identified as a prognostic marker for acute myeloid leukemia (AML) and other malignancies. , The chemokine receptor CXCR4 has been found to be a prognostic marker in various types of cancer, including breast cancer. , Upregulated expression of C-X-C chemokine receptor 4 is an independent prognostic predictor for patients with gastric cancer., detection of CXCR4 expression will be helpful for predicting prognosis for patients with gastric cancer., The chemokine receptor CXCR4 is a marker of metastatic disease., High CXCR4 level in cancer specimens independently predicts a poor outcome for patients with node-positive breast cancer., Univariate and multivariate analyses demonstrated that the high levels of nuclear CXCR4 and CXCL12 expression in hepatocytes were significantly better prognostic factors for overall and hepatic disease-free survival in patients with CLM., The chemokine receptor CXCR4 has been implicated in sarcoma development and has been found to be a prognostic marker for poor clinical outcome. , high CXCR4 expression is correlated to shorter DFS and could be used as a prognostic marker in order to stratify melanoma patients at higher progression risk.[SEP]Relations: C-X-C motif chemokine 12 receptor activity has relations: molfunc_protein with CXCR4, molfunc_protein with CXCR4. esophageal squamous cell carcinoma has relations: disease_protein with XRCC1, disease_protein with XRCC1, disease_protein with PRDX1, disease_protein with PRDX1, disease_protein with FBXW7, disease_protein with FBXW7. small cell lung carcinoma has relations: disease_protein with ASCL1, disease_protein with ASCL1. Definitions: esophageal squamous cell cancer defined as following: A carcinoma that originates usually from cells on the surface of the middle and lower third of the ESOPHAGUS. Tumor cells exhibit typical squamous morphology and form large polypoid lesions. Mutations in RNF6, LZTS1, TGFBR2, DEC1, and WWOX1 genes are associated with this cancer.. melanoma defined as following: A benign or malignant, primary or metastatic neoplasm affecting the melanocytes.. CXCL12 defined as following: A CXC chemokine that is chemotactic for T-LYMPHOCYTES and MONOCYTES. It has specificity for CXCR4 RECEPTORS. Two isoforms of CXCL12 are produced by alternative mRNA splicing.. cancer defined as following: A malignant tumor at the original site of growth.. acute myeloid leukemia defined as following: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.. chemokine C-X-C motif receptor 4 defined as following: This gene plays a role in immune cell chemotaxis and trafficking.. tumour defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. CXCR4 defined as following: Combining with the C-X-C motif chemokine 12 (CXCL12) and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. [GOC:bf, PMID:22204316]. breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. aggressiveness defined as following: Behavior which may be manifested by destructive and attacking action which is verbal or physical, by covert attitudes of hostility or by obstructionism.. sarcoma defined as following: A malignant neoplasm arising exclusively from the soft tissues.. gastric cancer defined as following: A primary or metastatic malignant neoplasm involving the stomach.. hepatocytes defined as following: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.. NSCLC defined as following: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.. malignancies defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. PDAC defined as following: A rare clinical entity including as main characteristics anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia. Only five cases have been reported so far, two of who were siblings. In the three nonfamilial cases, unilateral pulmonary agenesis and microphthalmia were associated with diaphragmatic hernia and pulmonary vessel agenesis. It has been suggested that two different entities can be distinguished: on one hand, the association of anophthalmia-pulmonary hypoplasia with/without anomalies of the face, heart, spleen and uterus, which may be due to a putative autosomal recessive gene with pleiotropic effects; on the other hand, a sporadic association including pulmonary hypoplasia, anophthalmia, unilateral diaphragmatic defect and agenesis of the pulmonary trunk, which may represent the expression of a developmental field defect. There is evidence that syndromic microphthalmia- is caused by homozygous or compound heterozygous mutation in the STRA6 gene on chromosome 15q24..", "label": "yes"} {"id": "converted_288", "sentence1": "Can zinc finger nucleases be used to combat disease?", "sentence2": "Genetic engineering has emerged as a powerful mechanism for understanding biological systems and a potential approach for redressing congenital disease., This is of particular importance, given the momentum currently behind ZFNs in moving into phase I clinical trials. This study provides a historical account of the origins of ZFN technology, an analysis of current techniques and applications, and an examination of the ethical issues applicable to translational ZFN genetic engineering in early phase clinical trials., This broad range of tractable species renders ZFNs a useful tool for improving the understanding of complex physiological systems, to produce transgenic animals, cell lines, and plants, and to treat human disease., We observe comparably high frequencies in human T cells, raising the possibility of strategies based on zinc-finger nucleases for the treatment of disease., Using engineered nucleases, such as Zinc Finger Nucleases (ZFNs) or Transcription Activator-Like Effector Nucleases (TALENs), to make targeted genomic modifications has become a common technique to create new model organisms and custom cell lines, and has shown great promise for disease treatment., Zinc Finger nucleases (ZFNs) have been used to create precise genome modifications at frequencies that might be therapeutically useful in gene therapy., Zinc finger nucleases as tools to understand and treat human diseases., Evaluation of novel design strategies for developing zinc finger nucleases tools for treating human diseases., An over expression APP model for anti-Alzheimer disease drug screening created by zinc finger nuclease technology., Oxidase-deficient neutrophils from X-linked chronic granulomatous disease iPS cells: functional correction by zinc finger nuclease-mediated safe harbor targeting., Recently, it has been shown that targeted mutagenesis using zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) can be used to generate knockout zebrafish lines for analysis of their function and/or developing disease models, Using engineered nucleases, such as Zinc Finger Nucleases (ZFNs) or Transcription Activator-Like Effector Nucleases (TALENs), to make targeted genomic modifications has become a common technique to create new model organisms and custom cell lines, and has shown great promise for disease treatment, Gene correction by homologous recombination with zinc finger nucleases in primary cells from a mouse model of a generic recessive genetic disease., raising the possibility of strategies based on zinc-finger nucleases for the treatment of disease.[SEP]Relations: C2H2 zinc finger domain binding has relations: molfunc_protein with ZXDC, molfunc_protein with ZXDC, molfunc_protein with EHMT1, molfunc_protein with EHMT1, molfunc_protein with ZXDA, molfunc_protein with ZXDA, molfunc_protein with LEF1, molfunc_protein with LEF1, molfunc_protein with EHMT2, molfunc_protein with EHMT2. Definitions: TALENs defined as following: Artificial nucleases that cleave DNA at a defined distance from specific DNA sequences recognized by TRANSCRIPTION ACTIVATOR-LIKE EFFECTORS. They are composed of an endodeoxyribonuclease fused to DNA-binding domains of the transcription activator-like effectors.. ZFN defined as following: Genetically engineered nucleases that cleave DNA at a defined distance from specific DNA sequences recognized by ZINC FINGER DNA-BINDING DOMAINS. They are composed of a DNA cleaving domain adapted from DNA endonucleases fused to a zinc finger DNA-binding domain.. zinc finger defined as following: Motifs in DNA- and RNA-binding proteins whose amino acids are folded into a single structural unit around a zinc atom. In the classic zinc finger, one zinc atom is bound to two cysteines and two histidines. In between the cysteines and histidines are 12 residues which form a DNA binding fingertip. By variations in the composition of the sequences in the fingertip and the number and spacing of tandem repeats of the motif, zinc fingers can form a large number of different sequence specific binding sites.. transgenic animals defined as following: Experimental organism whose genome has been altered by the transfer of a gene or genes from another species or breed.. human defined as following: Members of the species Homo sapiens.. iPS cells defined as following: Cells from adult organisms that have been reprogrammed into a pluripotential state similar to that of EMBRYONIC STEM CELLS.. zebrafish defined as following: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research.. mutagenesis defined as following: Production of genetic alterations by any technique, including chemicals, radiation, recombination, or other molecular biology methods.. cell lines defined as following: Established cell cultures that have the potential to propagate indefinitely.. congenital disease defined as following: existing at, and usually before, birth; referring to conditions that are present at birth, regardless of their causation; inborn metabolism disorders are generally not treed here.. plants defined as following: Multicellular, eukaryotic life forms of kingdom Plantae. Plants acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations. It is a non-taxonomical term most often referring to LAND PLANTS. In broad sense it includes RHODOPHYTA and GLAUCOPHYTA along with VIRIDIPLANTAE.. X-linked chronic granulomatous disease defined as following: An X-linked recessive form of chronic granulomatous disease caused by mutation(s) in the CYBB gene, encoding cytochrome b-245 beta chain..", "label": "yes"} {"id": "converted_1596", "sentence1": "Have thyronamines effects on fat tissue?", "sentence2": "Intraperitoneal or central injection of 3-T(1)AM or T(0)AM into mice, rats, or Djungarian hamsters caused various prompt effects, such as metabolic depression, hypothermia, negative chronotropy, negative inotropy, hyperglycemia, reduction of the respiratory quotient, ketonuria, and reduction of fat mass. [SEP]Relations: Ketonuria has relations: drug_effect with Propafenone, drug_effect with Propafenone, drug_effect with Streptozocin, drug_effect with Streptozocin, drug_effect with Acitretin, drug_effect with Acitretin, drug_effect with Rosiglitazone, drug_effect with Rosiglitazone, drug_effect with Carbamazepine, drug_effect with Carbamazepine. Definitions: rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. ketonuria defined as following: The presence of ketone bodies in the urine.. hypothermia defined as following:Cold weather can affect your body in different ways. You can get frostbite, which is an injury to the body that is caused by freezing. Your body can also lose heat faster than you can produce it. That can cause hypothermia, or abnormally low body temperature. It can make you sleepy, confused, and clumsy. Because it happens gradually and affects your thinking, you may not realize you need help. That makes it especially dangerous. A body temperature below 95 °F (35 °C) is a medical emergency and can lead to death if not treated promptly.
Anyone who spends much time outdoors in cold weather can get hypothermia. You can also get it from being cold and wet, or under cold water for too long. Babies and old people are especially at risk. Babies can get it from sleeping in a cold room.
Centers for Disease Control and Prevention
. fat tissue defined as following: Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white..", "label": "yes"} {"id": "converted_3033", "sentence1": "Is there a link between BCL11B haploinsufficiency and syndromic neurodevelopmental delay?", "sentence2": "BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells., Using massively parallel sequencing we identified 13 patients bearing heterozygous germline alterations in BCL11B. Notably, all of them are affected by global developmental delay with speech impairment and intellectual disability; however, none displayed overt clinical signs of immune deficiency. Six frameshift mutations, two nonsense mutations, one missense mutation, and two chromosomal rearrangements resulting in diminished BCL11B expression, arose de novo. A further frameshift mutation was transmitted from a similarly affected mother. Interestingly, the most severely affected patient harbours a missense mutation within a zinc-finger domain of BCL11B, probably affecting the DNA-binding structural interface, similar to the recently published patient. Furthermore, the most C-terminally located premature termination codon mutation fails to rescue the progenitor cell proliferation defect in hippocampal slice cultures from Bcl11b-deficient mice. Concerning the role of BCL11B in the immune system, extensive immune phenotyping of our patients revealed alterations in the T cell compartment and lack of peripheral type 2 innate lymphoid cells (ILC2s), consistent with the findings described in Bcl11b-deficient mice. Unsupervised analysis of 102 T lymphocyte subpopulations showed that the patients clearly cluster apart from healthy children, further supporting the common aetiology of the disorder. Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay. In addition, we suggest that missense mutations affecting specific sites within zinc-finger domains might result in distinct and more severe clinical outcomes., Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay. , Taken together, we show here that mutations leading either to BCL11B haploinsufficiency or to a truncated BCL11B protein clinically cause a non-syndromic neurodevelopmental delay.[SEP]Relations: Intellectual disability has relations: disease_phenotype_positive with macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, disease_phenotype_positive with macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, disease_phenotype_positive with neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination, disease_phenotype_positive with neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination. complex neurodevelopmental disorder has relations: disease_disease with developmental and epileptic encephalopathy, disease_disease with developmental and epileptic encephalopathy, disease_disease with X-linked complex neurodevelopmental disorder, disease_disease with X-linked complex neurodevelopmental disorder. syndrome with combined immunodeficiency has relations: disease_disease with pancytopenia due to IKZF1 mutations, disease_disease with pancytopenia due to IKZF1 mutations. Definitions: frameshift mutations defined as following: A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.. BCL11B defined as following: B-cell lymphoma/leukemia 11B (894 aa, ~96 kDa) is encoded by the human BCL11B gene. This protein may play a role in the modulation of p53-mediated signaling, tumor suppression and T cell development.. immune deficiency defined as following: Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.. T lymphocyte defined as following: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.. speech impairment defined as following: Acquired or developmental conditions marked by an impaired ability to comprehend or generate spoken forms of language.. neurodevelopmental disorder defined as following: A childhood disorder that has a neurological basis and manifests as a developmental disability.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. intellectual disability defined as following: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28).", "label": "no"} {"id": "converted_2618", "sentence1": "Can non ubiquitinated Tomm20 promote mitophagy?", "sentence2": " A total of 338 new targets were identified and from these we validated glycogen synthase kinase 3β (Gsk3β), which can phosphorylate α-synuclein, and translocase of outer mitochondrial membrane 20 (Tomm20), a mitochondrial translocase that, when ubiquitinated, promotes mitophagy, as SCFFbxo7substrates both in vitro and in vivo Ubiquitin chain restriction analyses revealed that Fbxo7 modified Gsk3β using K63 linkages. [SEP]Relations: NEK3 has relations: anatomy_protein_present with substantia nigra, anatomy_protein_present with substantia nigra, anatomy_protein_present with esophagus, anatomy_protein_present with esophagus, protein_protein with YWHAZ, protein_protein with YWHAZ, protein_protein with MIS18BP1, protein_protein with MIS18BP1, bioprocess_protein with mitotic cell cycle, bioprocess_protein with mitotic cell cycle. Definitions: glycogen synthase kinase 3β defined as following: This gene plays a role in neuronal morphogenesis.. translocase defined as following: A class of enzymes that catalyze the movement of ions or molecules across or within membranes..", "label": "no"} {"id": "converted_4681", "sentence1": "Is paxillin affected by RANKL?", "sentence2": "Western blotting assays presented upregulated expressions of TNF receptor-activating factor 6 (TRAF6) and integrin β3 induced by gingipains and RANKL compared to RANKL alone. Enhanced integrin-related signaling was also demonstrated by elevated phosphorylations of FAK and paxillin compared to control. Moreover, the pit resorption assays showed that gingipains augmented bone resorptive function of osteoclasts induced by RANKL. , paxillin levels induced by RANKL in murine bone marrow cells., RANKL promotes paxillin serine and tyrosine phosphorylation,[SEP]Relations: Protein S human has relations: drug_drug with Paclitaxel, drug_drug with Paclitaxel, drug_drug with Pirlindole, drug_drug with Pirlindole, drug_drug with Hexestrol, drug_drug with Hexestrol, drug_drug with Naftopidil, drug_drug with Naftopidil, drug_drug with Allylestrenol, drug_drug with Allylestrenol. Definitions: osteoclasts defined as following: A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.. RANKL defined as following: Human TNFSF11 wild-type allele is located within 13q14 and is approximately 45 kb in length. This allele, which encodes tumor necrosis factor ligand superfamily member 11 protein, plays a role in osteoclast differentiation and activation. This allele also is involved in apoptotic signal transduction and regulation.. paxillin defined as following: This gene plays a role in cytoskeleton remodeling.. TRAF6 defined as following: A signal transducing tumor necrosis factor receptor associated factor that is involved in regulation of NF-KAPPA B signalling and activation of JNK MITOGEN-ACTIVATED PROTEIN KINASES.. gingipains defined as following: Cysteine endoproteinases, from periodontal pathogen PORPHYROMONAS GINGIVALIS, acting as virulence factors associated with PERIODONTITIS. They are produced as pre-proproteins which mature into ARGININE and LYSINE specific endopeptidases.. FAK defined as following: A non-receptor protein tyrosine kinase with PROTEIN PHOSPHATASE 1 regulatory activity that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.. murine defined as following: Any of numerous species of small rodents belonging to the genus Mus and various related genera of the family Muridae..", "label": "yes"} {"id": "converted_909", "sentence1": "Does resveratrol reduce cardiac remodeling?", "sentence2": "In conclusion, resveratrol attenuated cardiac oxidative damage and left ventricular remodeling and enhanced the decreased expression of SIRT1 in hearts of old rats with emphysema and thus might be a therapeutic modality for cardiac injury complicated in chronic obstructive pulmonary disease (COPD)., In conclusion, resveratrol is a beneficial pharmacological tool that augments autophagy to bring about reverse remodeling in the postinfarction heart., Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function. These findings indicate that RSV can constitute an adjuvant therapeutic option in DCM prevention.[SEP]Relations: Resveratrol has relations: drug_drug with Dipyridamole, drug_drug with Dipyridamole, drug_drug with Acenocoumarol, drug_drug with Acenocoumarol, drug_drug with Tranilast, drug_drug with Tranilast, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Reteplase, drug_drug with Reteplase. Definitions: emphysema defined as following: Enlargement of air spaces distal to the TERMINAL BRONCHIOLES where gas-exchange normally takes place. This is usually due to destruction of the alveolar wall. Pulmonary emphysema can be classified by the location and distribution of the lesions.. resveratrol defined as following: A stilbene and non-flavonoid polyphenol produced by various plants including grapes and blueberries. It has anti-oxidant, anti-inflammatory, cardioprotective, anti-mutagenic, and anti-carcinogenic properties. It also inhibits platelet aggregation and the activity of several DNA HELICASES in vitro.. SIRT1 defined as following: A sirtuin family member found primarily in the CELL NUCLEUS. It is an NAD-dependent deacetylase with specificity towards HISTONES and a variety of proteins involved in gene regulation.. rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. COPD defined as following: A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.. RSV defined as following: A group of viruses in the PNEUMOVIRUS genus causing respiratory infections in various mammals. Humans and cattle are most affected but infections in goats and sheep have also been reported..", "label": "yes"} {"id": "converted_2973", "sentence1": "Have yeast prions become important models for the study of the basic mechanisms underlying human amyloid diseases?", "sentence2": "Endogenous yeast amyloids that control heritable traits and are frequently used as models for human amyloid diseases are termed yeast prions, Fibrous cross-β aggregates (amyloids) and their transmissible forms (prions) cause diseases in mammals (including humans) and control heritable traits in yeast. , These infectious yeast amyloidoses are outstanding models for the many common human amyloid-based diseases that are increasingly found to have some infectious characteristics., Yeast prions (infectious proteins) were discovered by their outré genetic properties and have become important models for an array of human prion and amyloid diseases., Yeast prions are models for both rare mammalian prion diseases and for several very common amyloidoses such as Alzheimer's disease, type 2 diabetes, and Parkinson's disease. , Yeast prions are important models for human amyloid diseases in general, particularly because new evidence is showing infectious aspects of several human amyloidoses not previously classified as prions. , Mechanism of amyloid formation is critical for a complete understanding of the yeast prion phenomenon and human amyloid-related diseases. , Yeast prions are important models for human amyloid diseases in general, particularly because new evidence is showing infectious aspects of several human amyloidoses not previously classified as prions., Endogenous yeast amyloids that control heritable traits and are frequently used as models for human amyloid diseases are termed yeast prions., Mechanism of amyloid formation is critical for a complete understanding of the yeast prion phenomenon and human amyloid-related diseases., Here we summarize the results of studies of prions of the yeast Saccharomyces cerevisiae and of the use of yeast model for investigation of some human amyloidoses, such as prion diseases, Alzheimer's, Parkinson's, and Huntington's diseases., Yeast prions increasingly are serving as models for the understanding and treatment of many mammalian amyloidoses., Yeast prions, based on self-seeded highly ordered fibrous aggregates (amyloids), serve as a model for human amyloid diseases., These infectious yeast amyloidoses are outstanding models for the many common human amyloid-based diseases that are increasingly found to have some infectious characteristics.**Description:**A polypeptide resulting from the translation of a gene.
. vertebrate defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes.. skeletal muscles defined as following: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles..", "label": "yes"} {"id": "converted_1910", "sentence1": "Could plasmepsins be used as targets for developing anti-malaria drugs?", "sentence2": "Fighting malaria: structure-guided discovery of nonpeptidomimetic plasmepsin inhibitors., Given that the parasite needs the resulting amino acid building blocks for its growth and development, plasmepsins are an important antimalarial drug target. , Due to early crystallographic evidence, plasmepsin II (Plm II) emerged as well explored target to develop novel antimalarials as well as a starting point to develop inhibitors targeting some other subtypes of plasmepsins i.e. Plm I, II, IV and V. With the advancements in drug discovery, several computational and synthetic approaches were employed in order to develop novel inhibitors targeting Plm II. , Structural basis for plasmepsin V inhibition that blocks export of malaria proteins to human erythrocytes., Plasmepsin V, an essential aspartyl protease of malaria parasites, has a key role in the export of effector proteins to parasite-infected erythrocytes. Consequently, it is an important drug target for the two most virulent malaria parasites of humans, Plasmodium falciparum and Plasmodium vivax., Plasmepsin V (PmV) is an essential Plasmodium protease and a highly promising antimalarial target, which still lacks molecular characterization and drug-like inhibitors., Our inhibitors act 'on-target', confirmed by cellular interference of PmV function and biochemical interaction with inhibitors. , Our work disclosed novel pursuable drug design strategies for highly efficient PmV inhibition highlighting novel molecular elements necessary for picomolar activity against PmV. All the presented data are discussed in respect to human aspartic proteases and previously reported inhibitors, highlighting differences and proposing new strategies for drug development., High binding likeness on antimalarial target plasmepsin was detected through molecular docking. , This provides the first direct evidence that PMV activity is essential for protein export in Plasmodium spp. and for parasite survival in human erythrocytes and validates PMV as an antimalarial drug target., The export mechanism involves the Plasmodium export element (PEXEL), which is a cleavage site for the parasite protease, Plasmepsin V (PMV). , Plasmepsin II (PM II) is an attractive target for anti-malaria drug discovery, which involves in host hemoglobin degradation in the acidic food vacuole., These methods are utilized to search for inhibitors of the aspartyl proteases, plasmepsin II and cathepsin D. Plasmepsin II, a protease found in the malaria parasite, hydrolyzes human hemoglobin, the nutrient source for the parasite and is a new target for anti-malaria therapy., Given recent advances in understanding the fundamental roles of the various plasmepsins, it is likely that the most effective antimalarial plasmepsin targets will be the non-digestive vacuole plasmepsins., Plasmepsins (PMs) are essential proteases of the plasmodia parasites and are therefore promising targets for developing drugs against malaria., Therefore, the plasmepsins of malaria parasites have been recognized as attractive antimalarial drug targets., As inhibition of plasmepsins leads to the parasite's death, these enzymes can be utilized as potential drug targets., falciparum plasmepsins II and IV make structure-based drug design of antimalarial compounds that focus on inhibiting plasmepsins possible., The malarial parasite encodes two homologous aspartic proteases, plasmepsins I and II, which are essential components of its hemoglobin-degradation pathway and are novel targets for antimalarial drug development., vivax plasmepsins (PvPMs) from different geographical regions are of utmost importance for drugs and vaccine designs for anti-malarial strategies., In P.falciparum, plasmepsins I, II, IV and HAP have been directly implicated in hemoglobin degradation during malaria infection, and are now considered targets for anti-malarial drug design., These results shed light on the role of V105 and T108 residues in plasmepsin specificities, and they should be useful in structure-based design of novel, selective inhibitors that may serve as antimalarial drugs., The aspartic proteases plasmepsins, whose inhibition leads to parasite death, are classified as targets for the design of potent drugs., A large compound library of about 1 million chemical compounds was docked on 5 different targets of plasmepsins using two different docking software, namely FlexX and AutoDock., Plasmodium aspartic proteases known as plasmepsins play an important role on haemoglobin degradation and are being studied as drug targets for chemotherapy of malaria., Our study revealed about 100 parasite-coded gene products that included many known drug targets such as Pf hypoxanthine guanine phosphoribosyl transferase, Pf L-lactate dehydrogenase, and Plasmepsins., The two aspartic proteases, plasmepsins I and II, from Plasmodium falciparum have recently emerged as potential targets., Plasmepsins are highly promising as drug targets, especially when combined with the inhibition of falcipains that are also involved in hemoglobin catabolism., Among such enzymes, Plasmepsins (aspartic proteases) and, especially, Falcipains (cysteine proteases) are highly promising antimalarial drug targets., The high sequence conservations between the plasmepsins from the isolates support the notion that the enzymes could be reliable targets for new antimalarial chemotherapeutics., Due to early crystallographic evidence, plasmepsin II (Plm II) emerged as well explored target to develop novel antimalarials as well as a starting point to develop inhibitors targeting some other subtypes of plasmepsins i.e., Plasmepsin, an aspartic protease, which is involved in the hemoglobin breakdown into smaller peptides emerged as a crucial target to develop new chemical entities to counter malaria., were employed in order to develop new chemical entities targeting Plm II., With the advancements in drug discovery, several computational and synthetic approaches were employed in order to develop novel inhibitors targeting Plm II., vivax plasmepsins (PvPMs) from different geographical regions are of utmost importance for drugs and vaccine designs for anti-malarial strategies.., We developed a potent inhibitor of plasmepsin V, called WEHI-842, which directly mimics the Plasmodium export element (PEXEL)., In order to validate appropriate use of PM4 as potential anti-malarial drug target, studies on genetic and structural variations among P., Over the past decade, much effort has been placed towards developing plasmepsin inhibitors as antimalarial agents, particularly targeting the digestive vacuole.[SEP]Relations: Plasmodium vivax malaria has relations: disease_disease with malaria, disease_disease with malaria. Plasmodium falciparum malaria has relations: disease_disease with malaria, disease_disease with malaria, disease_protein with FAS, disease_protein with FAS. Geneticin has relations: drug_drug with Plazomicin, drug_drug with Plazomicin. Plasmodium falciparum blood infection level has relations: disease_disease with malaria, disease_disease with malaria. Definitions: chemical compounds defined as following: A substance with a defined atomic or molecular structure that results from, or takes part in, reactions involving changes in its structure, composition, or properties.. amino acid defined as following: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.. hemoglobin defined as following: A tetrameric complex of 2 molecules of hemoglobin subunit alpha (encoded by either the HBA1 or HBA2 gene) and 2 molecules of hemoglobin subunit beta (encoded by the HBB gene).. parasites defined as following: Invertebrate organisms that live on or in another organism (the host), and benefit at the expense of the other. Traditionally excluded from definition of parasites are pathogenic BACTERIA; FUNGI; VIRUSES; and PLANTS; though they may live parasitically.. cathepsin defined as following: A carboxypeptidase that catalyzes the release of a C-terminal amino acid with a broad specificity. It also plays a role in the LYSOSOMES by protecting BETA-GALACTOSIDASE and NEURAMINIDASE from degradation. It was formerly classified as EC 3.4.12.1 and EC 3.4.21.13.. protease defined as following: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. Pf hypoxanthine guanine phosphoribosyl transferase defined as following: This gene is involved in purine/pyrimidine metabolism.. aspartyl proteases defined as following: A sub-subclass of endopeptidases that depend on an ASPARTIC ACID residue for their activity.. drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. aspartic protease defined as following: A subclass of peptide hydrolases that depend on an ASPARTIC ACID residue for their activity.. malaria defined as following: Vaccines made from antigens arising from any of the four strains of Plasmodium which cause malaria in humans, or from P. berghei which causes malaria in rodents.. haemoglobin defined as following: The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements.. cysteine proteases defined as following: A subclass of peptide hydrolases that depend on a CYSTEINE residue for their activity.. death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. digestive vacuole defined as following: Vacuole within a parasite used for digestion of the host cell cytoplasm. An example of this component is found in the Apicomplexa. [GOC:mb]. peptides defined as following: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.. humans defined as following: Members of the species Homo sapiens.. PMs defined as following: An exceedingly rare autosomal dominant developmental anomaly reported in 1986 in nine individuals among four generations of the same family. The syndrome has clinical characteristics of four-limb postaxial polydactyly and progressive myopia. There have been no further descriptions in the literature since 1986.. antimalarials defined as following: Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585).", "label": "yes"} {"id": "converted_4698", "sentence1": "Can autophagy related lncRNAs be used for colorectal cancer prognosis?", "sentence2": "A Novel Prognostic Prediction Model for Colorectal Cancer Based on Nine Autophagy-Related Long Noncoding RNAs, A prognostic prediction model of CRC was built based on nine ARlncRNAs (NKILA, LINC00174, AC008760.1, LINC02041, PCAT6, AC156455.1, LINC01503, LINC00957, and CD27-AS1). The 5-year overall survival rate was significantly lower in the high-risk group than in the low-risk group among train set, validation set, and all patients (all p < 0.001). The model had high sensitivity and accuracy in predicting the 1-year overall survival rate (area under the curve = 0.717). The prediction model risk score was an independent predictor of CRC. , The new ARlncRNA-based model predicts CRC patient prognosis and provides new research ideas regarding potential mechanisms regulating the biological behavior of CRC. ARlncRNAs may play important roles in personalized cancer treatment.[SEP]Relations: malignant colon neoplasm has relations: disease_disease with colorectal cancer, disease_disease with colorectal cancer, disease_protein with LGR5, disease_protein with LGR5, disease_protein with GCG, disease_protein with GCG, disease_protein with PPARG, disease_protein with PPARG, disease_protein with LRG1, disease_protein with LRG1. Definitions: CRC defined as following: The disappearance of all signs of cancer, including the absence of a detectable disease-related genetic abnormality, as determined by techniques such as karyotyping or FISH, in response to treatment..", "label": "yes"} {"id": "converted_4570", "sentence1": "Is AGO2 related to cytokinesis?", "sentence2": "AGO2 localizes to cytokinetic protrusions in a p38-dependent manner and is needed for accurate cell division., We suggest that AGO2 is part of a regulatory mechanism triggered by cytokinetic stress to generate the appropriate micro-environment for local transcript homeostasis.[SEP]Relations: Protein S human has relations: drug_drug with Bamet-UD2, drug_drug with Bamet-UD2, drug_drug with Peginterferon alfa-2b, drug_drug with Peginterferon alfa-2b, drug_drug with Interferon alfa-2b, drug_drug with Interferon alfa-2b, drug_drug with Peginterferon beta-1a, drug_drug with Peginterferon beta-1a, drug_drug with Cepeginterferon alfa-2B, drug_drug with Cepeginterferon alfa-2B. Definitions: AGO2 defined as following: Protein argonaute-2 (859 aa, ~97 kDa) is encoded by the human AGO2 gene. This protein plays a role in RNA catabolism.. transcript defined as following: The initial RNA molecule produced by transcription..", "label": "yes"} {"id": "converted_1108", "sentence1": "Is PLK2 involved in alpha-synuclein phosphorylation in Parkinson disease?", "sentence2": "An increase in α-synuclein levels due to gene duplications/triplications or impaired degradation is sufficient to trigger its aggregation and cause familial Parkinson disease , Here, we report that Polo-like kinase 2 (PLK2), an enzyme up-regulated in synucleinopathy-diseased brains, interacts with, phosphorylates and enhances α-synuclein autophagic degradation in a kinase activity-dependent manner., Polo-like kinase 2 regulates selective autophagic α-synuclein clearance and suppresses its toxicity in vivo, Collectively, our findings demonstrate that PLK2 is a previously undescribed regulator of α-synuclein turnover and that modulating its kinase activity could be a viable target for the treatment of synucleinopathies., α-Synuclein increased PLK2 levels and GSK-3β activity and increased the levels of phosphorylated α-Synuclein and Tau, Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system, Several neurological diseases, including Parkinson disease and dementia with Lewy bodies, are characterized by the accumulation of alpha-synuclein phosphorylated at Ser-129 (p-Ser-129), Here we submit evidence that polo-like kinase 2 (PLK2, also known as serum-inducible kinase or SNK) is a principle contributor to alpha-synuclein phosphorylation at Ser-129 in neurons., PLK2 directly phosphorylates alpha-synuclein at Ser-129 in an in vitro biochemical assay, These results indicate that PLK2 plays a critical role in alpha-synuclein phosphorylation in central nervous system.[SEP]Relations: synucleinopathy has relations: disease_disease with Parkinson disease, disease_disease with Parkinson disease. autosomal recessive Parkinson disease has relations: disease_disease with PLA2G6-associated neurodegeneration, disease_disease with PLA2G6-associated neurodegeneration, disease_protein with LRRK2, disease_protein with LRRK2, disease_protein with PLA2G6, disease_protein with PLA2G6, disease_protein with PRKN, disease_protein with PRKN. Definitions: polo-like kinase 2 defined as following: Serine/threonine-protein kinase PLK2 (685 aa, ~78 kDa) is encoded by the human PLK2 gene. This protein is involved in cell cycle progression, centriole duplication and serine/threonine phosphorylation.. α-synuclein defined as following: This gene plays a role in neuronal signaling.. Tau defined as following: A synthetic uridine pro-drug that is converted to uridine in vivo. Uridine, a pyrimidine nucleotide, has been used in a variety of diseases including depressive disorders and inherited myopathies. (NCI04). alpha-synuclein defined as following: A synuclein that is a major component of LEWY BODIES and plays a role in SYNUCLEINOPATHIES, neurodegeneration and neuroprotection.. PLK2 defined as following: This gene is involved in normal cell division.. synucleinopathies defined as following: Neurodegenerative disorders involving deposition of abnormal ALPHA-SYNUCLEIN in dopaminergic neurons and glial cells in the brain. Pathological aggregations of alpha-synuclein proteins results in LEWY BODIES and Lewy neurites; melanin granules in the SUBSTANTIA NIGRA and LOCUS COERULEUS; and glial cytoplasmic inclusions. Synucleinopathies are associated with mutation in the ALPHA-SYNUCLEIN (SNCA) gene on chromosome 4. PARKINSON DISEASE; LEWY BODY DISEASE with dementia; and MULTIPLE SYSTEM ATROPHY are prominent examples of synucleinopathy.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. serine defined as following: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.. dementia defined as following: The presence of dementia in an individual younger than age sixty five.. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM..", "label": "yes"} {"id": "converted_3359", "sentence1": "Is the FIP virus thought to be a mutated strain for the Feline enteric Coronavirus?", "sentence2": "Feline infectious peritonitis (FIP) results from mutations in the viral genome during a common feline enteric coronavirus (FECV) infection., It is caused by FIP virus (FIPV), a virulent mutant strain of Feline Enteric Coronavirus (FECV)., Feline infectious peritonitis virus (FIPV) was presumed to arise from mutations in the 3c of a ubiquitous and largely nonpathogenic feline enteric coronavirus (FECV)., Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV)., Feline infectious peritonitis (FIP) is a lethal systemic disease caused by FIP virus (FIPV), a virulent mutant of apathogenic feline enteric coronavirus (FECV)., Feline infectious peritonitis (FIP) is an almost invariably fatal feline coronavirus (FCoV)-induced disease thought to arise from a combination of viral mutations and an overexuberant immune response., BACKGROUND\n\nFeline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV)., BACKGROUND Feline Infectious Peritonitis (FIP) is a lethal systemic disease, caused by the FIP Virus (FIPV); a virulent mutant of Feline Enteric Coronavirus (FECV)., This coronavirus is a virulent mutant of the harmless, ubiquitous feline enteric coronavirus (FECV)., Feline infectious peritonitis virus (FIPV) was presumed to arise from mutations in the 3c of a ubiquitous and largely nonpathogenic feline enteric coronavirus (FECV)., Whilst intact in all FECVs, the 3c gene was mutated in the majority (71.4 %) of FIPVs, but not in all, implying that mutation in 3c is not the (single) cause of FIP.[SEP]Relations: feline infectious peritonitis has relations: disease_disease with Orthocoronavirinae infectious disease, disease_disease with Orthocoronavirinae infectious disease, disease_disease with Orthocoronavirinae infectious disease, disease_disease with Orthocoronavirinae infectious disease, disease_disease with cat disease, disease_disease with cat disease, disease_disease with cat disease, disease_disease with cat disease. Rotavirus infection has relations: disease_disease with Reoviridae infectious disease, disease_disease with Reoviridae infectious disease. Definitions: Feline infectious peritonitis defined as following: Common coronavirus infection of cats caused by the feline infectious peritonitis virus (CORONAVIRUS, FELINE). The disease is characterized by a long incubation period, fever, depression, loss of appetite, wasting, and progressive abdominal enlargement. Infection of cells of the monocyte-macrophage lineage appears to be essential in FIP pathogenesis.. feline defined as following: The formula to calculate body surface area in cats. It is mathematically defined as: BSA (m^2) = (10.1 x Weight(g)^2/3)/1000. viral genome defined as following: The complete genetic complement contained in a DNA or RNA molecule in a virus.. mutant defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. coronavirus defined as following: Virus diseases caused by the CORONAVIRUS genus. Some specifics include transmissible enteritis of turkeys (ENTERITIS, TRANSMISSIBLE, OF TURKEYS); FELINE INFECTIOUS PERITONITIS; and transmissible gastroenteritis of swine (GASTROENTERITIS, TRANSMISSIBLE, OF SWINE).. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. FECV defined as following: A species of CORONAVIRUS infecting cats of all ages and commonly found in catteries and zoos. Cats are often found carrying the virus but only a small proportion develop disease. Feline coronavirus and Feline infectious peritonitis virus (FIPV) are virtually the same virus in genetic and antigenetic terms, and are morphologically indistinguishable. Since they only differ in their disease potential (with FIPV causing a more serious illness), they are considered biotypes of each other.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"} {"id": "converted_2004", "sentence1": "Are there methods for generating highly multiplexed ChIP-seq libraries?", "sentence2": "A method for generating highly multiplexed ChIP-seq libraries., The barcoding of next generation sequencing libraries has become an essential part of the experimental design. Barcoding not only allows the sequencing of more than one sample per lane, but also reduces technical bias. However, current barcoding strategies impose significant limitations and/or technical barriers in their implementation for ChIP-sequencing.FINDINGS: Converting Y-shaped sequencing adapters to double stranded DNA prior to agarose gel size selection reduces adapter dimer contamination and quantitating the number of cycles required for amplification of the library with qPCR prior to library amplification eliminates library over-amplification.CONCLUSIONS: We describe an efficient and cost effective method for making barcoded ChIP-seq libraries for sequencing on the Illumina platform., A method for generating highly multiplexed ChIP-seq libraries, A method for generating highly multiplexed ChIP-seq libraries., We describe an efficient and cost effective method for making barcoded ChIP-seq libraries for sequencing on the Illumina platform..[SEP]Relations: heterochromatin organization involved in chromatin silencing has relations: bioprocess_protein with SMCHD1, bioprocess_protein with SMCHD1, bioprocess_bioprocess with heterochromatin organization, bioprocess_bioprocess with heterochromatin organization, bioprocess_bioprocess with heterochromatin maintenance, bioprocess_bioprocess with heterochromatin maintenance. double-stranded DNA binding has relations: molfunc_protein with CENPX, molfunc_protein with CENPX, molfunc_protein with APTX, molfunc_protein with APTX. Definitions: ChIP-seq defined as following: A molecular genetic technique that combines chromatin immunoprecipitation (ChIP) with massively parallel DNA sequencing to map the binding sites of DNA-associated proteins in a sample of cells. First, crosslinked protein-DNA complexes are isolated using ChIP. Next, the crosslinks are broken, the proteins are removed and the purified DNA is modified with adaptor oligonucleotides to facilitate massively parallel DNA sequencing. Following sequencing, the DNA sequences that are obtained can be mapped to their genomic locations..", "label": "yes"} {"id": "converted_432", "sentence1": "Is it possible to detect survivin protein expression in normal human adult tissues?", "sentence2": "Survivin (BIRC5) is one of the members of IAP-family apoptosis inhibitors. The BIRCS gene is expressed in most human embryonic tissues and malignant tumors but not in normal differentiated tissues of adult human., Survivin is an inhibitor of apoptosis that is undetectable in most terminally differentiated normal human tissues, strongly expressed in embryonic and fetal organs and is strongly expressed in many different human cancers., Survivin is a member of the inhibitor apoptosis family that is overexpressed in many malignancies. It has five known alternative splice forms, some of which differ in their antiapoptotic properties and expression levels in human cancers., survivin is usually not expressed in normal adult tissues,, AZD1152-hQPA induced caspase-dependent apoptosis of some cell lines, demonstrated by loss of mitochondrial membrane potential, activation of caspase-9, followed by activation of caspase-3. This effect was accompanied by the inhibition of survivin expression. In vivo efficacy was determined in NOD/SCID/γc(null) mice implanted with the Ramos human BL cell line. AZD1152 had anti-tumour effects in this murine xenograft model. There preclinical data suggest that the inhibition of Aurora B kinase is a potentially useful therapeutic strategy in BL and HL., a novel antiapoptosis gene, i.e., survivin, was identified as a structurally unique member of the inhibitor of apoptosis protein family. Survivin expression is turned off during fetal development and not found in non-neoplastic adult human tissues but is again turned on in the most common human cancers. The antiapoptotic properties of survivin might provide a significant growth advantage in tumors and possibly also contribute to chemoresistance of cancer., Further comparison of the distribution of PDEF with other widely recognized cancer-associated molecules showed that PDEF has more restricted distributions than Her-2/neu, Bcl-2, survivin or telomerase in cDNA libraries from normal human tissues and more increased distribution than Her-2/neu, CA-125, Bcl-2, survivin and telomerase in cDNA libraries from brain (except survivin), breast, lung and ovarian tumors. These data together show a better tumor-association for PDEF and suggest that PDEF is a more suitable target for developing specific cancer therapies., we identified decreased FHIT expression resulting in apoptosis inhibition and decreasing apoptosis associated with abnormal levels of some pro- and anti-apoptotic proteins (Bax, Bcl-2 and Survivin) by TUNEL and TMA. Our results demonstrated that the mutation in the FHIT gene significantly reduced FHIT expression in human CRC. Both TUNEL and TMA experiments demonstrated significantly inhibited apoptosis by down-regulation of Bax and up-regulation of Survivin and Bcl-2. Collectively, these studies identify the mechanism by which an important tumor suppressor gene, FHIT, inactivated specifically in human CRC, and contributes to our understanding of the mechanism of colorectal carcinogenesis.[SEP]Relations: PPP1R1A has relations: anatomy_protein_present with adult mammalian kidney, anatomy_protein_present with adult mammalian kidney, anatomy_protein_present with adipose tissue, anatomy_protein_present with adipose tissue, anatomy_protein_present with muscle tissue, anatomy_protein_present with muscle tissue, anatomy_protein_present with blood, anatomy_protein_present with blood. breast has relations: anatomy_protein_present with VIM, anatomy_protein_present with VIM. Definitions: Her-2/neu defined as following: Human Oncogene ErbB2 is a mutated variant of ERBB2 Gene, which encodes ERRB2 Receptor Protein Tyrosine Kinase, a 185-kDa type I membrane glycoprotein similar to EGFR that controls cell growth. Ligand binding increases ERBB2 tyrosine phosphorylation. A heterodimer with ERBB3 and ERBB4, p185ERBB2 is an essential component of the heregulin/neuregulin receptor. ERBB2 forms an IL6-dependent complex with IL6R gp130, resulting in ERBB2 tyrosine phosphorylation and MAPK activation. Oncogene ERBB2 disrupts normal cell function.. cancer defined as following: A malignant tumor at the original site of growth.. telomerase defined as following: An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.. Bcl-2 defined as following: The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.. breast defined as following: In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.. BIRC5 defined as following: Baculoviral IAP repeat-containing protein 5 (142 aa, ~16 kDa) is encoded by the human BIRC5 gene. This protein plays a role in the regulation of both apoptosis and the cell cycle.. BL defined as following: A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.. HL defined as following: A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen.. Survivin defined as following: Human BIRC5 wild-type allele is located in the vicinity of 17q25 and is approximately 10 kb in length. This allele, which encodes baculoviral IAP repeat-containing protein 5, is involved in the prevention of apoptotic cell death.. Bax defined as following: Apoptosis regulator BAX (192 aa, ~21 kDa) is encoded by the human BAX gene. This protein plays a role in both apoptosis and protein-protein interactions.. caspase-9 defined as following: A long pro-domain caspase that contains a CASPASE RECRUITMENT DOMAIN in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.. malignant tumors defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. TMA defined as following: A microvascular coagulopathy that may result from systemic vascular endothelial injury triggering the development of a procoagulant state, activation of the complement cascade, and microthrombi formation. Signs may include hemolytic anemia, thrombocytopenia, hypertension and renal dysfunction.. ovarian tumors defined as following: Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.. mitochondrial membrane defined as following: Either of the lipid bilayers that surround the mitochondrion and form the mitochondrial envelope. [GOC:mah, NIF_Subcellular:sao1045389829]. cDNA libraries defined as following: A collection of DNA molecules that have been cloned in vectors. In the case of a cDNA library the DNA inserts are copies of RNAs that have been reverse-transcribed into DNA prior to cloning.. Aurora B kinase defined as following: An aurora kinase that is a component of the chromosomal passenger protein complex and is involved in the regulation of MITOSIS. It mediates proper CHROMOSOME SEGREGATION and contractile ring function during CYTOKINESIS.. murine defined as following: Any of numerous species of small rodents belonging to the genus Mus and various related genera of the family Muridae.. cell lines defined as following: Established cell cultures that have the potential to propagate indefinitely.. PDEF defined as following: Human SPDEF wild-type allele is located in the vicinity of 6p21.3 and is approximately 19 kb in length. This allele, which encodes SAM pointed domain-containing Ets transcription factor, plays a role in transcriptional regulation.. FHIT defined as following: Bis(5'-adenosyl)-triphosphatase (147 aa, ~17 kDa) is encoded by the human FHIT gene. This protein is involved in nucleoside metabolism.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. caspase-3 defined as following: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.. tumor suppressor gene defined as following: Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.. human defined as following: Members of the species Homo sapiens.. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. CA-125 defined as following: A carbohydrate antigen that occurs in tumors of the ovary as well as in breast, kidney, and gastrointestinal tract tumors and normal tissue. While it is tumor-associated, it is not tumor-specific and may have a protective function against particles and infectious agents at mucosal surfaces.. survivin defined as following: Human BIRC5 wild-type allele is located in the vicinity of 17q25 and is approximately 10 kb in length. This allele, which encodes baculoviral IAP repeat-containing protein 5, is involved in the prevention of apoptotic cell death..", "label": "no"} {"id": "converted_930", "sentence1": "Is the length of the poly(A) tail involved in human disease?", "sentence2": "In human mitochondria, polyadenylation of mRNA, undertaken by the nuclear-encoded mitochondrial poly(A) RNA polymerase, is essential for maintaining mitochondrial gene expression. Our molecular investigation of an autosomal-recessive spastic ataxia with optic atrophy, present among the Old Order Amish, identified a mutation of MTPAP associated with the disease phenotype. When subjected to poly(A) tail-length assays, mitochondrial mRNAs from affected individuals were shown to have severely truncated poly(A) tails.[SEP]Relations: Mitochondrial inheritance has relations: disease_phenotype_positive with cyclic vomiting syndrome, disease_phenotype_positive with cyclic vomiting syndrome, disease_phenotype_positive with MELAS syndrome, disease_phenotype_positive with MELAS syndrome. Optic atrophy has relations: disease_phenotype_positive with distal monosomy 17q, disease_phenotype_positive with distal monosomy 17q, disease_phenotype_positive with distal monosomy 13q, disease_phenotype_positive with distal monosomy 13q, disease_phenotype_positive with Cockayne syndrome, disease_phenotype_positive with Cockayne syndrome. Definitions: molecular defined as following: Relating to or produced by or consisting of molecules.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. mitochondrial defined as following: The distribution of mitochondria, including the mitochondrial genome, into daughter cells after mitosis or meiosis, mediated by interactions between mitochondria and the cytoskeleton. [GOC:mcc, PMID:10873824, PMID:11389764]. optic atrophy defined as following: Atrophy of the optic disk which may be congenital or acquired. This condition indicates a deficiency in the number of nerve fibers which arise in the RETINA and converge to form the OPTIC DISK; OPTIC NERVE; OPTIC CHIASM; and optic tracts. GLAUCOMA; ISCHEMIA; inflammation, a chronic elevation of intracranial pressure, toxins, optic nerve compression, and inherited conditions (see OPTIC ATROPHIES, HEREDITARY) are relatively common causes of this condition.. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm..", "label": "yes"} {"id": "converted_1444", "sentence1": "Is arimoclomol a co-inducer of the heat shock response?", "sentence2": "Arimoclomol is a hydroxylamine derivative, a group of compounds which have unique properties as co-inducers of heat shock protein expression, but only under conditions of cellular stress. , In this review we summarize the evidence for the neuroprotective effects of enhanced heat shock protein expression by Arimoclomol and other inducers of the Heat Shock Response. , arimoclomol, a co-inducer of the heat shock stress response,, The heat-shock response (HSR) was activated in P23H retinae, and this was enhanced with arimoclomol treatment. , We also assessed these functions in mice treated with a known heat shock protein inducer, arimoclomol., Under conditions of excessive stress, arimoclomol induces amplification of the cytoprotective heat shock response in order to protect motor neurons from death. , Although both arimoclomol and celastrol induced the expression of Hsp70, Arimoclomol, an amplifier of heat shock protein expression involved in cellular stress response, has emerged as a potential therapeutic candidate in amyotrophic lateral sclerosis (ALS) in recent years., The mechanism of action of arimoclomol involves potentiation of the heat shock response, and treatment with arimoclomol increased Hsp70 expression. , Arimoclomol is an investigational drug for amyotrophic lateral sclerosis (ALS) that amplifies heat shock protein gene expression during cell stress., Arimoclomol, a coinducer of heat shock proteins, delayed progression of amyotrophic lateral sclerosis (ALS) in a mouse model in which motor neurons in the spinal cord and motor cortex degenerate.[SEP]Relations: Arimoclomol has relations: drug_protein with SOD1, drug_protein with SOD1. heat shock protein binding has relations: molfunc_protein with LMAN2, molfunc_protein with LMAN2, molfunc_protein with LMAN2, molfunc_protein with LMAN2, molfunc_protein with IRAK1, molfunc_protein with IRAK1, molfunc_protein with IRAK1, molfunc_protein with IRAK1. Definitions: death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. amyotrophic lateral sclerosis defined as following: A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94). Hsp70 defined as following: A family of structurally related proteins that are involved in both protein folding and cellular stress responses. The members of this family are approximately 70 kDa.. heat shock proteins defined as following: Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions.. heat shock protein defined as following: 78 kDa glucose-regulated protein (654 aa, ~72kDa) is encoded by HSPA5 gene. The protein is intracellularly localized in the endoplasmic reticulum lumen, and plays a role in the assembly of multimeric protein complexes inside the organelle. In addition, the protein is thought to function as a pro-survival protein, or an inhibitor of apoptosis.. HSR defined as following: The integration of epidemiologic, sociological, economic, and other analytic sciences in the study of health services. Health services research is usually concerned with relationships between need, demand, supply, use, and outcome of health services. The aim of the research is evaluation, particularly in terms of structure, process, output, and outcome. (From Last, Dictionary of Epidemiology, 2d ed). motor neurons defined as following: Neurons which send impulses peripherally to activate muscles or secretory cells.. spinal cord defined as following: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER..", "label": "yes"} {"id": "converted_4291", "sentence1": "Is histone variant H3.3K27M associated with gliomas?", "sentence2": "Reciprocal H3.3 gene editing identifies K27M and G34R mechanisms in pediatric glioma including NOTCH signaling., Well-known oncohistones, with mutations on both H3.1 and H3.3, include H3K36M in chondroblastoma, H3K27M in glioma, Diffuse intrinsic pontine gliomas (DIPG) are the most aggressive brain tumors in children with 5-year survival rates of only 2%. About 85% of all DIPG are characterized by a lysine-to-methionine substitution in histone 3, which leads to global H3K27 hypomethylation accompanied by H3K27 hyperacetylation. [SEP]Relations: chondroblastoma (disease) has relations: disease_protein with H3-3B, disease_protein with H3-3B. histone lysine methylation has relations: bioprocess_bioprocess with histone H3-K27 methylation, bioprocess_bioprocess with histone H3-K27 methylation, bioprocess_bioprocess with histone H3-K37 methylation, bioprocess_bioprocess with histone H3-K37 methylation, bioprocess_bioprocess with histone H3-K36 methylation, bioprocess_bioprocess with histone H3-K36 methylation. Glioma has relations: disease_phenotype_positive with chromosome 17q11.2 deletion syndrome, 1.4Mb, disease_phenotype_positive with chromosome 17q11.2 deletion syndrome, 1.4Mb. Definitions: H3.1 defined as following: This gene is involved in the regulation of chromosome dynamics.. DIPG defined as following: A glioma that grows diffusely in the pons. It usually affects children and has a poor prognosis.. glioma defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21). chondroblastoma defined as following: A usually benign tumor composed of cells which arise from chondroblasts or their precursors and which tend to differentiate into cartilage cells. It occurs primarily in the epiphyses of adolescents. It is relatively rare and represents less than 2% of all primary bone tumors. The peak incidence is in the second decade of life; it is about twice as common in males as in females. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p1846). H3K27 defined as following: The lysine residue found at amino acid position 28 in the histone H3 protein. Methylation of this residue may be a marker for transcriptionally repressed genes.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. gliomas defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21).", "label": "yes"} {"id": "converted_815", "sentence1": "Is indicated the use of antioxidant supplements in patients at risk for coronary artery disease?", "sentence2": "We and others have published observational epidemiologic studies in support of vitamins in the primary prevention of CVD, but the results from intervention studies are mixed., For vitamin E, observational data suggest benefit at doses of 100 to 400 IU/d. Results from recent large-scale trials are mixed, with some showing modest benefit but others suggesting no benefit, especially for secondary prevention. Results for B vitamins are also mixed and further complicated by the recent folate fortification of the flour supply. If greater B vitamin intake does reduce CVD, the benefits are likely to be greatest for primary prevention and in populations with intake below dietary reference standards. , In the dose-response meta-analysis, each 30 mg/day increase in vitamin C, 30 IU/day increase in vitamin E, and 1 mg/day increase in beta-carotene yielded the estimated overall relative risk for CHD of 1.01 (95% CI, 0.99-1.02), 0.96 (95% CI, 0.94-0.99), and 1.00 (95% CI, 0.88-1.14), respectively. CONCLUSIONS: Our findings in this meta-analysis suggest that an increase in dietary intake of antioxidant vitamins has encouraging prospects for possible CHD prevention., High levels of α-tocopherol in serum were associated with 30% lower CAD risk in another study (HR 0.71; 95%CI 0.53-0.94). Among minerals (zinc, selenium, and chromium), an inverse association between zinc and CAD was observed; levels lower than 14.1 µmol/L were associated with an increased risk for CAD (RR 1.70; 95%CI 1.21-2.38)., The information available on this issue is scarce. Further prospective studies are needed to elucidate the role of these nutrients in the cardiovascular risk of patients with diabetes., Coenzyme Q10 supplementation at a dosage of 150 mg appears to decrease the inflammatory marker IL-6 in patients with CAD., Coenzyme Q10 supplements at a dose of 150 mg can decrease oxidative stress and increase antioxidant enzyme activity in patients with CAD. A higher dose of coenzyme Q10 supplements (>150 mg/d) might promote rapid and sustainable antioxidation in patients with CAD., Alpha-tocopherol or beta-carotene supplementation has no protective effect on macrovascular outcomes or total mortality of diabetic male smokers., Sodium selenite supplementation increases GPx-1 activity in endothelial cells and in CAD patients. Future studies have to demonstrate whether long-term CAD outcome can be improved., After 7.3 years of treatment and follow-up, a combination pill of folic acid, vitamin B6, and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women, despite significant homocysteine lowering., In this population-based study, vitamin E use was unrelated to mortality, but this apparently null finding seems to represent a combination of increased mortality in those with severe cardiovascular disease and a possible protective effect in those without., In this large cohort of apparently healthy US male physicians, self-selected supplementation with vitamin E, vitamin C, or multivitamins was not associated with a significant decrease in total CVD or CHD mortality. , The American Heart Association has recommended consumption of a balanced diet with emphasis on antioxidant-rich fruits and vegetables but has made no recommendations regarding vitamin E supplementation for the general population. Although vitamin E supplementation seems to be safe for most people, recommendations from health care professionals should reflect the uncertainty of established benefit as demonstrated in clinical trials, Recent studies show that supplementation with antioxidant vitamins E and C have benefits in CHD prevention; however, supplementation with beta-carotene may have deleterious effects and is not recommended. Current evidence suggests that patients with CHD would probably benefit from taking vitamin E in a dosage of 400 IU per day and vitamin C in a dosage of 500 to 1,000 mg per day. Clinicians may also want to consider vitamin supplementation for CHD prevention in high-risk patients. Folate lowers elevated homocysteine levels, but evidence for routine supplemental use does not yet exist. , In patients at high risk for cardiovascular events, treatment with vitamin E for a mean of 4.5 years had no apparent effect on cardiovascular outcomes.[SEP]Relations: cardiovascular disease has relations: contraindication with Antipyrine, contraindication with Antipyrine, contraindication with Amoxapine, contraindication with Amoxapine, contraindication with Methionine, contraindication with Methionine, contraindication with Fentanyl, contraindication with Fentanyl, contraindication with Carbinoxamine, contraindication with Carbinoxamine. Definitions: Alpha-tocopherol defined as following: A natural tocopherol and one of the most potent antioxidant tocopherols. It exhibits antioxidant activity by virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus. It has four methyl groups on the 6-chromanol nucleus. The natural d form of alpha-tocopherol is more active than its synthetic dl-alpha-tocopherol racemic mixture.. IL-6 defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine interleukin-6 (IL-6) with antiapoptotic, proinflammatory, antiinflammatory, proproliferative and proangiogenic activities. IL-6 binds to its receptor (IL-6R), activating a receptor-CD130 receptor complex; the CD130 portion of the complex is a signal transduction protein that activates JAK kinases and Ras-mediated signaling pathways, which in turn activate downstream signaling pathways, resulting in the activation of various transcription factors (STAT, ELK-1, NF-IL-6, etc.) and gene transcription. The physiological effects of IL-6 are complex and varied and include hematopoietic, pyrogenic and thermogenic, proinflammatory, antiinflammatory, proproliferative (anti-apoptotic), and angiogenic effects.. Folate defined as following: A cofactor for 1-carbon transfer involved with DNA synthesis.. nutrients defined as following: Various components of food that are required for nourishment.. vitamin B6 defined as following: The 4-methanol form of VITAMIN B 6 which is converted to PYRIDOXAL PHOSPHATE which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. Although pyridoxine and Vitamin B 6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading (EE Snell; Ann NY Acad Sci, vol 585 pg 1, 1990).. minerals defined as following: Native, inorganic or fossilized organic substances having a definite chemical composition and formed by inorganic reactions. They may occur as individual crystals or may be disseminated in some other mineral or rock. (Grant & Hackh's Chemical Dictionary, 5th ed; McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed). beta-carotene defined as following: A carotenoid that is a precursor of VITAMIN A. Beta carotene is administered to reduce the severity of photosensitivity reactions in patients with erythropoietic protoporphyria (PORPHYRIA, ERYTHROPOIETIC).. endothelial cells defined as following: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.. cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. folic acid defined as following: A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.. Coenzyme Q10 defined as following: A lipid-soluble benzoquinone which is involved in ELECTRON TRANSPORT in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals.. diabetes defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.. cardiovascular defined as following: The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body.. coronary artery disease defined as following: Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause..", "label": "no"} {"id": "converted_2669", "sentence1": "Is CXCL7 a chemokine?", "sentence2": "CXCL7, a chemokine highly expressed in platelets, , Chemokine CXCL7 Heterodimers[SEP]Relations: Chemokine receptors bind chemokines has relations: pathway_protein with CXCL8, pathway_protein with CXCL8, pathway_protein with CXCL5, pathway_protein with CXCL5, pathway_protein with CXCL6, pathway_protein with CXCL6, pathway_protein with CXCL9, pathway_protein with CXCL9, pathway_protein with CXCL11, pathway_protein with CXCL11. Definitions: platelets defined as following: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation.. CXCL7 defined as following: Human PPBP wild-type allele is located within 4q12-q13 and is approximately 1 kb in length. This allele, which encodes platelet basic protein, plays a role in chemotaxis, neutrophil activation and a variety of other cellular processes.. chemokine defined as following: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C; (CHEMOKINES, C); CC; (CHEMOKINES, CC); and CXC; (CHEMOKINES, CXC); according to variations in a shared cysteine motif..", "label": "yes"} {"id": "converted_3788", "sentence1": "Is Semagacestat effective for Alzheimer's Disease?", "sentence2": "However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer's disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects. , BACKGROUND: In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's disease (AD)., CONCLUSION: In participants with mild to moderate AD, high dose semagacestat treatment was associated with greater severity and faster worsening of NPS in a pattern resembling an agitated depression. , INTRODUCTION: The negative efficacy study examining the γ-secretase inhibitor semagacestat in mild to moderate Alzheimer's disease (AD) included a number of biomarkers of the disease as well as safety outcomes., A clinical trial with the wide-spectrum γ-secretase inhibitor semagacestat has, however, demonstrated that global inhibition of all γ-secretases causes serious toxicity. , ESULTS: Semagacestat treatment was associated with increased reporting of suspected Notch-related adverse events (gastrointestinal, infection, and skin cancer related). Other relevant safety findings associated with semagacestat treatment included cognitive and functional worsening, skin-related TEAEs, renal and hepatic changes, increased QT interval, and weight loss. , CONCLUSIONS: As compared with placebo, semagacestat did not improve cognitive status, and patients receiving the higher dose had significant worsening of functional ability., RESULTS: The trial was terminated before completion on the basis of a recommendation by the data and safety monitoring board., The ADAS-cog scores worsened in all three groups (mean change, 6.4 points in the placebo group, 7.5 points in the group receiving 100 mg of the study drug, and 7.8 points in the group receiving 140 mg; P=0.15 and P=0.07, respectively, for the comparison with placebo). The ADCS-ADL scores also worsened in all groups (mean change at week 76, -9.0 points in the placebo group, -10.5 points in the 100-mg group, and -12.6 points in the 140-mg group; P=0.14 and P<0.001, respectively, for the comparison with placebo). Patients treated with semagacestat lost more weight and had more skin cancers and infections, treatment discontinuations due to adverse events, and serious adverse events (P<0.001 for all comparisons with placebo). , Recently disclosed Phase III findings on semagacestat indicated that Alzheimer's disease (AD) patients on this drug showed significantly worsened cognitive function compared to those treated with placebo., The recent failure of semagacestat in two large Phase III studies questions the value of γ-secretase inhibitors in treating Alzheimer's disease., ntly disclosed Phase III findings on semagacestat indicated that Alzheimer's disease (AD) patients on this drug showed significantly worsened cognitive function compared to those treated with placebo. Since, ts from Phase III studies showed that semagacestat failed to slow disease progression, and it was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living. Furthermore, sem, rge Phase III clinical trials of semagacestat in mild-to-moderate AD patients were prematurely interrupted because of the observation of a detrimental cognitive and functional effect of the drug. These detrimental ef, BACKGROUND: In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's d, However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer's disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects., However, the preliminary equivocal cognitive results obtained with bapineuzumab as well as the detrimental cognitive effects observed with semagacestat, a potent γ-secretase inhibitor, raise the possibility that targeting Aβ may not be clinically efficacious in AD.[SEP]Relations: familial Alzheimer disease has relations: disease_disease with Alzheimer disease, disease_disease with Alzheimer disease, disease_phenotype_positive with Perseveration, disease_phenotype_positive with Perseveration, disease_protein with PRNP, disease_protein with PRNP, disease_disease with inherited prion disease, disease_disease with inherited prion disease. cognitive disorder has relations: disease_disease with dementia (disease), disease_disease with dementia (disease). Definitions: drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. renal defined as following: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.. NPS defined as following: A syndrome of multiple abnormalities characterized by the absence or hypoplasia of the PATELLA and congenital nail dystrophy. It is a genetically determined autosomal dominant trait.. skin cancer defined as following: A primary or metastatic malignant neoplasm involving the skin. Primary malignant skin neoplasms most often are carcinomas (either basal cell or squamous cell carcinomas) or melanomas. Metastatic malignant neoplasms to the skin include carcinomas and lymphomas.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. bapineuzumab defined as following: A humanized monoclonal antibody (IgG1) raised against amyloid beta peptides with Alzheimer disease treatment application. Bapineuzumab recognizes and binds the N-terminal amino acids 1-5 of the amyloid beta peptide, and may be used in a passive immunotherapy treatment.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. cognitive deficits defined as following: Disorders characterized by disturbances in mental processes related to learning, thinking, reasoning, and judgment.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. weight loss defined as following: The measured decrease in body weight over a specified period of time..", "label": "no"} {"id": "converted_4679", "sentence1": "Is there any role of the 'Greek islands' in olfactory receptor choice?", "sentence2": "Chromatin conformation capture using in situ Hi-C on fluorescence-activated cell-sorted olfactory sensory neurons and their progenitors shows that olfactory receptor gene clusters from 18 chromosomes make specific and robust interchromosomal contacts that increase with differentiation of the cells. These contacts are orchestrated by intergenic olfactory receptor enhancers, the 'Greek islands', which first contribute to the formation of olfactory receptor compartments and then form a multi-chromosomal super-enhancer that associates with the single active olfactory receptor gene. The Greek-island-bound transcription factor LHX2 and adaptor protein LDB1 regulate the assembly and maintenance of olfactory receptor compartments, Greek island hubs and olfactory receptor transcription, providing mechanistic insights into and functional support for the role of trans interactions in gene expression.[SEP]Relations: olfactory receptor activity has relations: molfunc_protein with OR2AK2, molfunc_protein with OR2AK2, molfunc_protein with OR2A42, molfunc_protein with OR2A42, molfunc_protein with OR7E24, molfunc_protein with OR7E24, molfunc_protein with OR2K2, molfunc_protein with OR2K2, molfunc_protein with OR5AK2, molfunc_protein with OR5AK2. Definitions: LDB1 defined as following: Human LDB2 wild-type allele is located in the vicinity of 4p16 and is approximately 397 kb in length. This allele, which encodes LIM domain-binding protein 2, plays a role in the modulation of gene transcription.. chromosomes defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.. olfactory receptor defined as following: Neurons in the OLFACTORY EPITHELIUM with proteins (RECEPTORS, ODORANT) that bind, and thus detect, odorants. These neurons send their DENDRITES to the surface of the epithelium with the odorant receptors residing in the apical non-motile cilia. Their unmyelinated AXONS synapse in the OLFACTORY BULB of the BRAIN.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary..", "label": "yes"} {"id": "converted_3431", "sentence1": "Is ozanezumab effective for amyotrophic lateral sclerosis?", "sentence2": "The adjusted mean of the joint-rank score was -14·9 (SE 13·5) for the ozanezumab group and 15·0 (13·6) for the placebo group, with a least squares mean difference of -30·0 (95% CI -67·9 to 7·9; p=0·12). , INTERPRETATION: Ozanezumab did not show efficacy compared with placebo in patients with ALS. Therefore, Nogo-A does not seem to be an effective therapeutic target in ALS., INTERPRETATION\n\nOzanezumab did not show efficacy compared with placebo in patients with ALS., The adjusted mean of the joint-rank score was -14·9 (SE 13·5) for the ozanezumab group and 15·0 (13·6) for the placebo group, with a least squares mean difference of -30·0 (95% CI -67·9 to 7·9; p=0·12)., INTERPRETATION Ozanezumab did not show efficacy compared with placebo in patients with ALS., The adjusted mean of the joint-rank score was -14·9 (SE 13·5) for the ozanezumab group and 15·0 (13·6) for the placebo group, with a least squares mean difference of -30·0 (95% CI -67·9 to 7·9; p=0·12).[SEP]Relations: amyotrophic lateral sclerosis has relations: disease_protein with TIAM1, disease_protein with TIAM1, disease_protein with WNT7A, disease_protein with WNT7A, disease_protein with SLC6A1, disease_protein with SLC6A1, disease_protein with CHMP2B, disease_protein with CHMP2B, disease_protein with TMSB4X, disease_protein with TMSB4X. Definitions: ALS defined as following: A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94). amyotrophic lateral sclerosis defined as following: An inherited form of amyotrophic lateral sclerosis, usually inherited in an autosomal dominant pattern, caused by mutation(s) in the SOD1 gene, encoding superoxide dismutase..", "label": "no"} {"id": "converted_370", "sentence1": "Is intense physical activity associated with longevity?", "sentence2": "Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners., Death rates declined with increased levels of total activity (estimated in kilocalories), and declined also with increased intensity of effort measured as from none, to light, to moderately vigorous or vigorous sports play. Death rates at any given quantity of physical exercise were lower for men playing moderately intense sports than for less vigorous men., he purpose of this study was to investigate if jogging, which can be very vigorous, is associated with increased all-cause mortality in men and women., This long-term study of joggers showed that jogging was associated with significantly lower all-cause mortality and a substantial increase in survival for both men and women., Light activities (<4 multiples of resting metabolic rate (METs)) were not associated with reduced mortality rates, moderate activities (4-<6 METs) appeared somewhat beneficial, and vigorous activities (> or =6 METs) clearly predicted lower mortality rates (p, trend = 0.72, 0.07, and <0.001, respectively)., These data demonstrate a graded inverse relationship between total physical activity and mortality. Furthermore, vigorous activities but not nonvigorous activities were associated with longevity., The capacity for prolonged and vigorous physical exercise, particularly if the exercise is recreational, is a strong indicator of longevity.[SEP]Relations: Cessation of head growth has relations: disease_phenotype_positive with Angelman syndrome due to a point mutation, disease_phenotype_positive with Angelman syndrome due to a point mutation, phenotype_phenotype with Secondary microcephaly, phenotype_phenotype with Secondary microcephaly, disease_phenotype_positive with Angelman syndrome due to paternal uniparental disomy of chromosome 15, disease_phenotype_positive with Angelman syndrome due to paternal uniparental disomy of chromosome 15, disease_phenotype_positive with Angelman syndrome due to maternal 15q11q13 deletion, disease_phenotype_positive with Angelman syndrome due to maternal 15q11q13 deletion, disease_phenotype_positive with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies, disease_phenotype_positive with neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies. Definitions: Death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions..", "label": "yes"} {"id": "converted_384", "sentence1": "Is nintedanib effective for Idiopathic Pulmonary Fibrosis?", "sentence2": "In this review, we present the positive results of recently published clinical trials regarding therapy for IPF, with emphasis on pirfenidone and nintedanib., Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis, In the Phase II TOMORROW trial, treatment with 150 mg of nintedanib twice daily showed a trend to slow the decline in lung function and significantly decrease acute exacerbations in patients with IPF, while showing an acceptable safety profile. The Phase III INPULSIS trials demonstrated a significant decrease in the annual rate of decline in forced vital capacity in IPF patients treated with 150 mg nintedanib twice daily. In the INPULSIS-2 trial, the time to the first acute exacerbation significantly increased in IPF patients who were treated with 150 mg of nintedanib twice daily., Effects on collagen secretion were compared with those of the drugs nintedanib and pirfenidone, recently approved for IPF., Nintedanib, an orally available, small-molecule tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) receptors has recently been shown, in two pivotal phase III studies, to effectively slow IPF disease progression. Consequently, nintedanib was given accelerated approval by the FDA in October 2014 for the treatment of IPF. , Most recently, pirfenidone and nintedanib, two compounds with pleiotropic anti-fibrotic properties, have been proven effective in reducing functional decline and disease progression in IPF. , Meningococcal group B vaccine (Trumenba) to prevent more types of invasive meningococcal disease; antihemophilic factor (recombinant), porcine sequence (Obizur) to treat bleeding from acquired hemophilia A; and pirfenidone (Esbriet) and nintedanib (Ofev) for idiopathic pulmonary fibrosis., More importantly, the period ends with the publication of two groundbreaking studies that confirmed that two drugs, pirfenidone and nintedanib, slowed disease progression, leading to a historic approval by the FDA. , Nintedanib (Ofev(®)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. Nintedanib has received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use for the treatment of IPF, and for the second-line treatment in combination with docetaxel of locally advanced, metastatic or locally recurrent non-small cell lung cancer of adenocarcinoma tumour histology. , This article summarizes the milestones in the development of nintedanib leading to this first approval for IPF., Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis., Nintedanib: a novel therapeutic approach for idiopathic pulmonary fibrosis., Nintedanib is in clinical development as a treatment for idiopathic pulmonary fibrosis (IPF)., Reducing lung function decline in patients with idiopathic pulmonary fibrosis: potential of nintedanib., These results suggest that nintedanib may impact the progressive course of fibrotic lung diseases such as idiopathic pulmonary fibrosis., Findings from recently published placebo-controlled trials in idiopathic pulmonary fibrosis have established that pirfenidone and nintedanib prevent about 50% of the decline in forced vital capacity typically seen in this disease; future trials are therefore unlikely to use placebo as a control group for ethical reasons., The tyrosine kinase inhibitor nintedanib (BIBF 1120) is in clinical development for the treatment of idiopathic pulmonary fibrosis., A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis., A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. , Data from the Phase II TOMORROW study suggested that nintedanib 150�mg twice daily had clinical benefits with an acceptable safety profile.METHODS: The INPULSIS� trials are replicate Phase III, randomized, double-blind, studies comparing the efficacy and safety of nintedanib 150�mg twice daily with placebo in patients with IPF. , Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. , The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2. CONCLUSIONS: In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients. , A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. METHODS: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. , Nintedanib (Ofev(�)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. , Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis., A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis.[SEP]Relations: idiopathic pulmonary fibrosis has relations: disease_disease with pulmonary fibrosis, disease_disease with pulmonary fibrosis, disease_protein with WNT5A, disease_protein with WNT5A, disease_protein with MUC5B, disease_protein with MUC5B, disease_protein with RTEL1, disease_protein with RTEL1, disease_protein with HIF1A, disease_protein with HIF1A. Definitions: tyrosine kinase defined as following: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.. cancer defined as following: A malignant tumor at the original site of growth.. platelet-derived growth factor defined as following: Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.. vascular endothelial growth factor defined as following: A recombinant therapeutic agent which is chemically identical to or similar to endogenous vascular endothelial growth factor (VEGF). Produced by a wide variety of cell types, endogenous VEGF is a homodimeric, glycosylated protein that is a highly specific mitogen for vascular endothelial cells; significantly influences vascular permeability; appears to play a role in neovascularisation under physiological conditions; is a potent chemoattractant; has pro-coagulatory activities; and is hypoxia-inducible. Therapeutic VEGF may be used to induce angiogenesis in the treatment of ischemic conditions and may have a role in stimulating nerve regeneration. (NCI04). hemophilia A defined as following: A deficiency or abnormality of a blood coagulation factor characterized by the tendency to hemorrhage. Hemophilia is typically a hereditary disorder but, rarely, may be acquired. Inherited coagulation factor-deficient hemophilias include hemophilia A or classic hemophilia (hereditary factor VIII deficiency) hemophilia B or Christmas disease (hereditary factor IX deficiency), and hemophilia C (hereditary factor XI deficiency). Factor VIII inhibitors may occur spontaneously as autoantibodies, resulting in acquired hemophilia known as acquired factor VIII deficiency. Approximately 10% of patients with acquired hemophilia have an underlying malignancy.. Medicinal Products defined as following: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.. VEGF defined as following: The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as \"tumor angiogenesis factor\" and \"vascular permeability factor\". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.. collagen defined as following: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).. IPF defined as following: A common interstitial lung disease of unknown etiology, usually occurring between 50-70 years of age. Clinically, it is characterized by an insidious onset of breathlessness with exertion and a nonproductive cough, leading to progressive DYSPNEA. Pathological features show scant interstitial inflammation, patchy collagen fibrosis, prominent fibroblast proliferation foci, and microscopic honeycomb change.. pirfenidone defined as following: An orally bioavailable and deuterated form of the synthetic antifibrotic agent pirfenidone, with potential anti-inflammatory and anti-fibrotic activities. Upon administration, deupirfenidone inhibits a variety of pro-inflammatory mediators, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and transforming growth factor-beta (TGF-b). This may reduce fibrosis, inflammation and infection, and may repair the impaired lymphatic flow, decrease lymphedema and restore lymphatic function. In the lungs, deupirfenidone may abrogate impaired lung function, lymphoedema and pulmonary fibrosis.. nintedanib defined as following: An orally bioavailable, indolinone-derived inhibitor of multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs), with potential antiangiogenic, antifibrotic and antineoplastic activities. Upon administration, nintedanib selectively binds to and inhibits vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and colony stimulating factor 1 receptor (CSF1R) tyrosine kinases, which may result in the induction of endothelial cell apoptosis, the reduction in tumor vasculature, the inhibition of tumor cell proliferation and migration, and antifibrotic activity in pulmonary fibrosis. In addition, nintedanib also binds to and inhibits members of the Src family of tyrosine kinases, including Src, Lck and Lyn, and fms-like tyrosine kinase 3 (FLT-3). VEGFR, FGFR, PDGFR and CSF1R RTKs play key roles in tumor angiogenesis, tumor cell proliferation and metastasis, as well as pulmonary fibrosis.. diarrhea defined as following: An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.. fibroblast growth factor defined as following: A recombinant therapeutic agent which is chemically identical to or similar to endogenous fibroblast growth factor 1 (FGF-1. Because of the mitogenic and angiogenetic effects of FGF-1 on fibroblasts and endothelial cells, therapeutic FGF-1 has a potential role in wound healing; because FGF-1 has been shown to induce neurogenesis, therapeutic FGF-1 may have a role in nerve regeneration. (NCI04). Human defined as following: Members of the species Homo sapiens.. bleeding defined as following: Bleeding or escape of blood from a vessel.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. docetaxel defined as following: A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER.. non-small cell lung cancer defined as following: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.. tyrosine kinase inhibitor defined as following: Protein kinase inhibitors that inhibit TYROSINE PROTEIN KINASES.. Idiopathic Pulmonary Fibrosis defined as following: A common interstitial lung disease of unknown etiology, usually occurring between 50-70 years of age. Clinically, it is characterized by an insidious onset of breathlessness with exertion and a nonproductive cough, leading to progressive DYSPNEA. Pathological features show scant interstitial inflammation, patchy collagen fibrosis, prominent fibroblast proliferation foci, and microscopic honeycomb change..", "label": "yes"} {"id": "converted_1267", "sentence1": "Does HER2 under-expression lead to favorable response to trastuzumab?", "sentence2": "over-expression of HER2 is reported in approximately 20% of gastric tumours, challenging the use of targeted therapies. , In patients with advanced gastric or gastro-oesophageal junction cancer, addition of trastuzumab to chemotherapy significantly improved overall survival compared with chemotherapy alone. Addition of trastuzumab to chemotherapy did not increase the incidence of adverse events., treatment of HER2-overexpressing breast cancer: trastuzumab,, Trastuzumab has demonstrated clinical activity in several types of HER2-overexpressing epithelial tumors, such as breast and metastatic gastric or gastroesophageal junction cancer. , An example is the established benefit of trastuzumab as adjuvant therapy for breast cancer; a clear definition of HER2-positivity and the assay reproducibility have, however, remained unanswered. , Trastuzumab is a monoclonal antibody targeted to the Her2 receptor and approved for treatment of Her2-positive breast cancer., Human epidermal growth factor receptor 2 (HER2/neu) is an important target for the treatment of the breast cancers in which it is overexpressed. However, no approved anti-HER2/neu therapy is available for the majority of breast cancer patients, who express HER2/neu at low levels (with scores of 1+ or 2+/fluorescence in situ hybridization-negative)., The humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin) is useful in the treatment of ErbB2-overexpressing breast cancers,, HercepTestTM (DAKO A/S, Glostrup, Denmark) is an immunohistochemical assay that detects HER2/neu gene products, and evaluates the overexpression status of the HER2/neu protein in determining eligibility for the Trastuzumab (HerceptinR, Genentech, San Francisco, CA, USA) therapy. [SEP]Relations: Trastuzumab has relations: drug_protein with ERBB2, drug_protein with ERBB2, drug_drug with Yersinia pestis 195/p antigen (formaldehyde inactivated), drug_drug with Yersinia pestis 195/p antigen (formaldehyde inactivated), drug_drug with Clostridium tetani toxoid antigen (formaldehyde inactivated), drug_drug with Clostridium tetani toxoid antigen (formaldehyde inactivated), drug_drug with Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated), drug_drug with Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated), drug_drug with XmAb 2513, drug_drug with XmAb 2513. Definitions: breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. HER2 defined as following: Human ERBB2 wild-type allele is located in the vicinity of 17q21.1 and is approximately 29 kb in length. This allele, which encodes receptor tyrosine-protein kinase erbB-2 protein, plays a role in EGF receptor signal transduction pathways and cellular growth. Amplification or overexpression of this gene is involved in the progression of several forms of cancer, including breast and ovarian tumors.. breast defined as following: In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.. Her2-positive breast cancer defined as following: A biologic subset of breast carcinoma defined by high expression of HER2, GRB7, and TRAP100, and by lack of expression of estrogen receptor (ER).. trastuzumab defined as following: A humanized monoclonal antibody against the ERBB-2 RECEPTOR (HER2). As an ANTINEOPLASTIC AGENT, it is used to treat BREAST CANCER where HER2 is overexpressed.. monoclonal antibody defined as following: A humanized monoclonal antibody directed against parathyroid hormone-related protein (PTH-rP). As a poly-hormone with diverse biological roles, PTH-rP is expressed by normal tissues, acting in local tissue environments in a variety of ways; it is commonly overexpressed by breast, prostate, and other cancers, acting systemically by promoting bone resorption, inhibiting calcium excretion from the kidney, inducing hypercalcemia, and possibly playing a role in the formation of bony metastases. By blocking the effects of PTH-rP on calcium metabolism, monoclonal antibody CAL may inhibit cancer-related hypercalcemia. (NCI04).", "label": "no"} {"id": "converted_3240", "sentence1": "Can mitochondria transfer from cell to cell?", "sentence2": "Interest in the recently discovered phenomenon of mitochondrial transfer between mammalian cells has gained momentum since it was first described in cell culture systems more than a decade ago., We show evidence that mitochondria transfer from Jurkat cells to MSCs, which is mediated by cell adhesion, This process of mitochondria transfer is mediated by tunneling nanotubes, which are protrusions that extend from the cell membrane .[SEP]Relations: mitochondrion has relations: cellcomp_protein with TH, cellcomp_protein with TH, cellcomp_protein with CS, cellcomp_protein with CS, cellcomp_protein with NNT, cellcomp_protein with NNT, cellcomp_protein with HIBADH, cellcomp_protein with HIBADH, cellcomp_protein with CAT, cellcomp_protein with CAT. Definitions: mitochondria defined as following: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed). cell membrane defined as following: Any of the lipid bilayer membranes within a cell.. Jurkat cells defined as following: A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.. MSCs defined as following: Enables the transmembrane transfer of an ion by a channel that opens in response to a mechanical stress and when a cyclic nucleotide has been bound by the channel complex or one of its constituent parts. [GOC:jl, PMID:22206667].", "label": "yes"} {"id": "converted_528", "sentence1": "Is there any software for automated analysis of immuno-histochemistry images?", "sentence2": "The LIM homeobox gene Lhx2 is expressed in cortical progenitors during development and also in the superficial layers of the neocortex in maturity. However, analysis of Lhx2 function at later stages of cortical development has been hampered by severe phenotypes associated with early loss of function. , The vein graft samples were obtained on each time point after surgery. The expression of the EDRz transfected in the vein graft was detected using a fluorescent microscope. Early growth response gene-1 (Egr-1) mRNA was measured using reverse transcription-PCR and in situ hybridization. And the protein expression of Egr-1 was detected by using western blot and immunohistochemistry analyses., Tissue Transglutaminase (TG2) is a multifunctional enzyme, which amongst other functions, is involved in cell differentiation. Therefore, we hypothesized that TG2 contributes to differentiation of OPCs into OLGs and thereby stimulates remyelination. [SEP]Relations: neocortex has relations: anatomy_protein_present with ENO2, anatomy_protein_present with ENO2, anatomy_protein_present with TMCO3, anatomy_protein_present with TMCO3, anatomy_protein_present with TMCO6, anatomy_protein_present with TMCO6. Protein S human has relations: drug_drug with Ifosfamide, drug_drug with Ifosfamide, drug_drug with Ifosfamide, drug_drug with Ifosfamide. Definitions: TG2 defined as following: Protein-glutamine gamma-glutamyltransferase 2 (687 aa, ~77 kDa) is encoded by the human TGM2 gene. This protein plays a role in both the induction of apoptosis and the formation of covalent bonds between peptide-bound glutamine and various primary amines.. neocortex defined as following: The largest portion of the CEREBRAL CORTEX in which the NEURONS are arranged in six layers in the mammalian brain: molecular, external granular, external pyramidal, internal granular, internal pyramidal and multiform layers.. Egr-1 defined as following: Early growth response protein 1 (543 aa, ~58 kDa) is encoded by the human EGR1 gene. This protein is involved in the modulation of both mitogenesis and differentiation through the transcriptional regulation of specified genes.. Lhx2 defined as following: Human LHX2 wild-type allele is located within 9q33-34.1 and is approximately 22 kb in length. This allele, which encodes the LIM/homeobox protein Lhx2, may play a role in both the modulation of transcription by RNA polymerase II and the development of lymphoid and neural cells.. Tissue Transglutaminase defined as following: Calcium-dependent acyltransferase that catalyzes cross-linking of proteins at a GLUTAMINE in one chain with primary amine such as in LYSINE in another chain. In addition it can also accept monoamine substrates to catalyze post-translational modifications (e.g., protein serotonylation).. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm..", "label": "yes"} {"id": "converted_790", "sentence1": "Is recommended the use of perioperative treatment with thyroid hormone therapy in patients undergoing coronary artery bypass grafting?", "sentence2": "Short duration postoperative iv T(3) therapy increases cardiac index and does not alter mortality., We conclude that although widespread interest has been shown on the use of thyroid hormones in the perioperative period, and the effect of cardiopulmonary bypass on thyroid hormone metabolism widely studied, there is no substantial evidence to justify routine use of thyroid hormones in patients undergoing coronary artery bypass grafting., There is no clear evidence at this point to support thyroid hormone replacement in the latter patients, and it may be potentially harmful. Rather, we hold that T3 treatment of various surgical and other patients with nonthyroidal illness should be deferred until proof of its therapeutic efficacy is demonstrated., Perioperative administration of triiodothyronine increased cardiac output slightly and decreased systemic vascular resistance, but it had no effect on operative outcome. Routine use after coronary surgery is thus not recommended., Although mild effects on myocardial performance may exist, we cannot recommend at this time the routine use of intravenous T(3) as an inotropic agent in patients undergoing coronary artery bypass graft surgery., Raising serum triiodothyronine concentrations in patients undergoing coronary-artery bypass surgery increases cardiac output and lowers systemic vascular resistance, but does not change outcome or alter the need for standard postoperative therapy., Thus, there seems to be no sound justification for a routine use of T3 in patients undergoing open-heart procedures.[SEP]Relations: Liothyronine has relations: contraindication with coronary artery disease, contraindication with coronary artery disease, contraindication with pituitary hormone defiency from vascular origin, contraindication with pituitary hormone defiency from vascular origin, contraindication with thyroid crisis (disease), contraindication with thyroid crisis (disease), contraindication with combined pituitary hormone deficiencies, genetic form, contraindication with combined pituitary hormone deficiencies, genetic form. response to thyroid hormone has relations: bioprocess_bioprocess with response to hormone, bioprocess_bioprocess with response to hormone. Definitions: triiodothyronine defined as following: A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.. thyroid hormones defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs..", "label": "no"} {"id": "converted_3243", "sentence1": "Does GRHL2 over-expression lead to EMT?", "sentence2": "Grhl2 is down-regulated in disseminated cancer cells that have undergone EMT, and over-expression of Grhl2 is sufficient to induce epithelial gene expression., Grhl2 plays an essential role in the determination of epithelial phenotype of breast cancers, EMT and tumor progression., In breast cancer cell lines, shRNA-mediated knockdown of GRHL2 expression or functional inactivation of GRHL2 using dominant negative GRHL2 proteins induces down-regulation of ERBB3 gene expression, a striking reduction in cell proliferation, and morphological and phenotypical alterations characteristic of an epithelial-to-mesenchymal transition (EMT), thus implying contradictory roles of GRHL2 in breast carcinogenesis., Interestingly, we could further demonstrate that expression of GRHL2 is directly suppressed by the transcription factor zinc finger enhancer-binding protein 1 (ZEB1), which in turn is a direct target for repression by GRHL2, suggesting that the EMT transcription factors GRHL2 and ZEB1 form a double negative regulatory feedback loop in breast cancer cells, Mesenchymal-Epithelial Transition in Sarcomas Is Controlled by the Combinatorial Expression of MicroRNA 200s and GRHL2., transcription factor--Grainyhead-like 2 (GRHL2) maintains the epithelial phenotype, We explored the role of grainyhead-like 2 (GRHL2), a suppressor of EMT, in the progression of PDAC, GRHL2 knockdown CFPAC-1 cells demonstrated morphological changes into mesenchymal appearances and reduced proliferation through EMT, The transcription factor grainyhead-like 2 (GRHL2) plays a crucial role in various developmental processes, Grainyhead-like 2 (Grhl2), a transcription factor, has been reported to be associated with several tumor processes including EMT. , Grhl2 antagonizes transforming growth factor-β (TGFβ)-induced EMT[SEP]Relations: GRHL2 has relations: protein_protein with ESR1, protein_protein with ESR1, protein_protein with PIAS2, protein_protein with PIAS2, protein_protein with GRHL1, protein_protein with GRHL1, protein_protein with DDIT4L, protein_protein with DDIT4L, protein_protein with GRHL3, protein_protein with GRHL3. Definitions: Grhl2 defined as following: This gene plays a role in embyronic brain development and in epithelial development and maintenance.. ERBB3 gene defined as following: This gene is involved in signal transduction pathways that result in cellular proliferation or differentiation. The gene has also been associated with numerous cancers.. transcription factor defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. EMT defined as following: A transition where an epithelial cell loses apical/basolateral polarity, severs intercellular adhesive junctions, degrades basement membrane components and becomes a migratory mesenchymal cell. [GOC:dph, PMID:14701881]. breast cancers defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. ZEB1 defined as following: This gene is involved in the transcriptional repression of interleukin 2.. Grainyhead-like 2 defined as following: Human GRHL2 wild-type allele is located in the vicinity of 8q22.3 and is approximately 186 kb in length. This allele, which encodes grainyhead-like protein 2 homolog protein, is involved in development and maintenance of epithelial tissues and neurulation. Mutation of the gene is associated with non-syndromic sensorineural deafness autosomal dominant type 28.. Sarcomas defined as following: A malignant neoplasm arising exclusively from the soft tissues.. PDAC defined as following: A rare clinical entity including as main characteristics anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia. Only five cases have been reported so far, two of who were siblings. In the three nonfamilial cases, unilateral pulmonary agenesis and microphthalmia were associated with diaphragmatic hernia and pulmonary vessel agenesis. It has been suggested that two different entities can be distinguished: on one hand, the association of anophthalmia-pulmonary hypoplasia with/without anomalies of the face, heart, spleen and uterus, which may be due to a putative autosomal recessive gene with pleiotropic effects; on the other hand, a sporadic association including pulmonary hypoplasia, anophthalmia, unilateral diaphragmatic defect and agenesis of the pulmonary trunk, which may represent the expression of a developmental field defect. There is evidence that syndromic microphthalmia- is caused by homozygous or compound heterozygous mutation in the STRA6 gene on chromosome 15q24.. cancer cells defined as following: Cells of, or derived from, a malignant tumor.. GRHL2 defined as following: This gene plays a role in embyronic brain development and in epithelial development and maintenance..", "label": "no"} {"id": "converted_1992", "sentence1": "Is there a role of proton beam therapy in medulloblastoma treatment?", "sentence2": "All papers directly compared outcomes from protons with photons, five papers included medulloblastoma, four papers each included craniopharyngioma and low grade gliomas and three papers included ependymoma., There are many indications of protontherapy for paediatric brain tumours in curative intent, either for localized treatment of ependymomas, germ-cell tumours, craniopharyngiomas, low-grade gliomas; or panventricular irradiation of pure non-secreting germinoma; or craniospinal irradiation of medulloblastomas and metastatic pure germinomas., Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood., BACKGROUND: The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood.METHODS: We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy., Evaluation of permanent alopecia in pediatric medulloblastoma patients treated with proton radiation., BACKGROUND: To precisely calculate skin dose and thus to evaluate the relationship between the skin dose and permanent alopecia for pediatric medulloblastoma patients treated with proton beams., CONCLUSIONS: Our results based on 12 patients provide a relationship between the skin dose and permanent alopecia for pediatric medulloblastoma patients treated with protons. , Proton beam craniospinal irradiation reduces acute toxicity for adults with medulloblastoma., PURPOSE: Efficacy and acute toxicity of proton craniospinal irradiation (p-CSI) were compared with conventional photon CSI (x-CSI) for adults with medulloblastoma., CONCLUSIONS: This report is the first analysis of clinical outcomes for adult medulloblastoma patients treated with p-CSI. , Dilemmas concerning dose distribution and the influence of relative biological effect in proton beam therapy of medulloblastoma., OBJECTIVE: To improve medulloblastoma proton therapy., The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood., The aim of this study is to evaluate the cost-effectiveness of proton beam therapy with cochlear dose reduction compared with conventional X-ray radiotherapy for medulloblastoma in childhood.We developed a Markov model to describe health states of 6-year-old children with medulloblastoma after treatment with proton or X-ray radiotherapy, All patients completed therapy without interruption.Our proton-beam technique for craniospinal irradiation of pediatric medulloblastoma has successfully reduced normal-tissue doses and acute treatment-related sequelae, Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuro-ectodermal tumors: spinal theca irradiation, For 6 MV x-rays > 60% of the dose prescribed to the target was delivered to 44% of the heart volume, while the proton beam was able to completely avoid the heart, the liver, and in all likelihood the thyroid and gonads as well.The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET, Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuroectodermal tumors: reduction of the supratentorial target volume, This review describes the role of radiation in general and proton therapy in particular for the treatment of medulloblastoma, central nervous system primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, and the recently described embryonal tumor with multilayered rosettes, Reducing toxicity from craniospinal irradiation: using proton beams to treat medulloblastoma in young children., Intensity-modulated radiotherapy did show more bladder dose reduction than the other techniques in pelvic sarcoma irradiation.CONCLUSIONS: In the diseases studied, using various techniques of 3D-CRT, electrons, IMRT, and protons, protons are most optimal in treating retinoblastomas, medulloblastomas (posterior fossa and craniospinal), and pelvic sarcomas., For 6 MV x-rays>60% of the dose prescribed to the target was delivered to 44% of the heart volume, while the proton beam was able to completely avoid the heart, the liver, and in all likelihood the thyroid and gonads as well.CONCLUSION: The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET., In medulloblastoma, three posterior fossa irradiation techniques were analyzed: 3D-CRT, IMRT, and protons., Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuro-ectodermal tumors: spinal theca irradiation., Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuroectodermal tumors: reduction of the supratentorial target volume., The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET., Cost-effectiveness analysis of cochlear dose reduction by proton beam therapy for medulloblastoma in childhood., Dilemmas concerning dose distribution and the influence of relative biological effect in proton beam therapy of medulloblastoma., To improve medulloblastoma proton therapy., Our proton-beam technique for craniospinal irradiation of pediatric medulloblastoma has successfully reduced normal-tissue doses and acute treatment-related sequelae., Treatment planning with protons for pediatric retinoblastoma, medulloblastoma, and pelvic sarcoma: how do protons compare with other conformal techniques?[SEP]Relations: Medulloblastoma has relations: disease_phenotype_positive with mismatch repair cancer syndrome, disease_phenotype_positive with mismatch repair cancer syndrome, disease_phenotype_positive with medulloblastoma, disease_phenotype_positive with medulloblastoma, disease_phenotype_positive with pleuropulmonary blastoma, disease_phenotype_positive with pleuropulmonary blastoma, disease_phenotype_positive with Li-Fraumeni syndrome, disease_phenotype_positive with Li-Fraumeni syndrome, disease_phenotype_positive with Gardner syndrome, disease_phenotype_positive with Gardner syndrome. Definitions: protons defined as following: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion.. bladder defined as following: A musculomembranous sac along the URINARY TRACT. URINE flows from the KIDNEYS into the bladder via the ureters (URETER), and is held there until URINATION.. retinoblastomas defined as following: A malignant tumor arising from the nuclear layer of the retina that is the most common primary tumor of the eye in children. The tumor tends to occur in early childhood or infancy and may be present at birth. The majority are sporadic, but the condition may be transmitted as an autosomal dominant trait. Histologic features include dense cellularity, small round polygonal cells, and areas of calcification and necrosis. An abnormal pupil reflex (leukokoria); NYSTAGMUS, PATHOLOGIC; STRABISMUS; and visual loss represent common clinical characteristics of this condition. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2104). pelvic sarcoma defined as following: Sarcoma involving the organs and structures of the pelvis.. embryonal tumor defined as following: A usually malignant neoplasm composed of primitive (immature) tissues that resemble fetal tissues. Medulloblastoma, ependymoblastoma, pineoblastoma, and Wilms tumor are representative embryonal neoplasms.. craniopharyngiomas defined as following: A benign pituitary-region neoplasm that originates from Rathke's pouch. The two major histologic and clinical subtypes are adamantinous (or classical) craniopharyngioma and papillary craniopharyngioma. The adamantinous form presents in children and adolescents as an expanding cystic lesion in the pituitary region. The cystic cavity is filled with a black viscous substance and histologically the tumor is composed of adamantinomatous epithelium and areas of calcification and necrosis. Papillary craniopharyngiomas occur in adults, and histologically feature a squamous epithelium with papillations. (From Joynt, Clinical Neurology, 1998, Ch14, p50). ependymomas defined as following: Glioma derived from EPENDYMOGLIAL CELLS that tend to present as malignant intracranial tumors in children and as benign intraspinal neoplasms in adults. It may arise from any level of the ventricular system or central canal of the spinal cord. Intracranial ependymomas most frequently originate in the FOURTH VENTRICLE and histologically are densely cellular tumors which may contain ependymal tubules and perivascular pseudorosettes. Spinal ependymomas are usually benign papillary or myxopapillary tumors. (From DeVita et al., Principles and Practice of Oncology, 5th ed, p2018; Escourolle et al., Manual of Basic Neuropathology, 2nd ed, pp28-9). gonads defined as following: The gamete-producing glands, OVARY or TESTIS.. germinomas defined as following: A malignant neoplasm of the germinal tissue of the GONADS; MEDIASTINUM; or pineal region. Germinomas are uniform in appearance, consisting of large, round cells with vesicular nuclei and clear or finely granular eosinophilic-staining cytoplasm. (Stedman, 265th ed; from DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, pp1642-3). gliomas defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21). medulloblastoma defined as following: A malignant neoplasm that may be classified either as a glioma or as a primitive neuroectodermal tumor of childhood (see NEUROECTODERMAL TUMOR, PRIMITIVE). The tumor occurs most frequently in the first decade of life with the most typical location being the cerebellar vermis. Histologic features include a high degree of cellularity, frequent mitotic figures, and a tendency for the cells to organize into sheets or form rosettes. Medulloblastoma have a high propensity to spread throughout the craniospinal intradural axis. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2060-1). toxicity defined as following: The finding of bodily harm due to the poisonous effects of something..", "label": "yes"} {"id": "converted_2542", "sentence1": "Is polyadenylation a process that stabilizes a protein by adding a string of Adenosine residues to the end of the molecule?", "sentence2": "The addition of poly(A) tails to eukaryotic nuclear mRNAs promotes their stability, export to the cytoplasm and translation. , Most eukaryotic genes express mRNAs with alternative polyadenylation sites at their 3' ends, Polyadenylation is the non-template addition of adenosine nucleotides at the 3'-end of RNA, which occurs after transcription and generates a poly(A) tail up to 250-300 nucleotides long., Polyadenylation is a process of endonucleolytic cleavage of the mRNA, followed by addition of up to 250 adenosine residues to the 3' end of the mRNA., Plant mitochondrial polyadenylated mRNAs are degraded by a 3'- to 5'-exoribonuclease activity, which proceeds unimpeded by stable secondary structures., We show that a 3'- to 5'-exoribonuclease activity is responsible for the preferential degradation of polyadenylated mRNAs as compared with non-polyadenylated mRNAs, and that 20-30 adenosine residues constitute the optimal poly(A) tail size for inducing degradation of RNA substrates in vitro., The diversity of polyadenylation sites suggests that mRNA polyadenylation in prokaryotes is a relatively indiscriminate process that can occur at all mRNA's 3'-ends and does not require specific consensus sequences as in eukaryotes., Polyadenylation of premessenger RNAs occurs posttranscriptionally in the nucleus of eukaryotic cells by cleavage of the precursor and polymerization of adenosine residues., However, under certain conditions, poly(A) tracts may lead to mRNA stabilization., From these results, we propose that in plant mitochondria, poly(A) tails added at the 3' ends of mRNAs promote an efficient 3'- to 5'- degradation process.., Auxiliary downstream elements are required for efficient polyadenylation of mammalian pre-mRNAs., Transcription in these cells is polycistronic. Tens to hundreds of protein-coding genes of unrelated function are arrayed in long clusters on the same DNA strand. Polycistrons are cotranscriptionally processed by trans-splicing at the 5' end and polyadenylation at the 3' end, generating monocistronic units ready for degradation or translation, We have devised a simple chromatographic procedure which isolates five polyadenylation factors that are required for polyadenylation of eukaryotic mRNA. , During mammalian oocyte maturation, protein synthesis is mainly controlled through cytoplasmic polyadenylation of stored maternal mRNAs., Identification and characterization of a polyadenylated small RNA (s-poly A+ RNA) in dinoflagellates., Thus, polyadenylation seems to be a major component of the RNA editing machinery that affects overlapping genes in animal mitochondria., Pre-mRNA 3'-end processing, the process through which almost all eukaryotic mRNAs acquire a poly(A) tail is generally inhibited during the cellular DNA damage, Almost all eukaryotic mRNAs possess 3' ends with a polyadenylate (poly(A)) tail., We previously demonstrated, by limited mutagenesis, that conserved sequence elements within the 5' end of influenza virus virion RNA (vRNA) are required for the polyadenylation of mRNA in vitro., Polyadenylation of mRNA precursors by poly(A) polymerase depends on two specificity factors and their recognition sequences, The majority of eukaryotic pre-mRNAs are processed by 3'-end cleavage and polyadenylation, Formation of mRNA 3' termini involves cleavage of an mRNA precursor and polyadenylation of the newly formed end. , The polyadenylation of RNA is a near-universal feature of RNA metabolism in eukaryotes., The mechanism of RNA degradation in Escherichia coli involves endonucleolytic cleavage, polyadenylation of the cleavage product by poly(A) polymerase, and exonucleolytic degradation by the exoribonucleases, , The addition of poly(A)-tails to RNA is a process common to almost all organisms. , The addition of poly(A) tails to RNA is a phenomenon common to all organisms examined so far. , The addition of poly(A)-tails to RNA is a phenomenon common to almost all organisms. , Polyadenylation contributes to the destabilization of bacterial mRNA.[SEP]Relations: RNA polyadenylation has relations: bioprocess_protein with TENT4A, bioprocess_protein with TENT4A, bioprocess_protein with TENT4A, bioprocess_protein with TENT4A, bioprocess_protein with PAPOLA, bioprocess_protein with PAPOLA, bioprocess_protein with PAPOLA, bioprocess_protein with PAPOLA, bioprocess_protein with PAPOLG, bioprocess_protein with PAPOLG. Definitions: mitochondria defined as following: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed). mutagenesis defined as following: Production of genetic alterations by any technique, including chemicals, radiation, recombination, or other molecular biology methods.. adenosine defined as following: A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.. eukaryotic cells defined as following: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane.. consensus sequences defined as following: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known CONSERVED SEQUENCE set is represented by a consensus sequence. Commonly observed supersecondary protein structures (AMINO ACID MOTIFS) are often formed by conserved sequences.. nucleotides defined as following: The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed). cytoplasm defined as following: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990). genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. polyadenylation defined as following: The enzymatic addition of a sequence of adenylyl residues at the 3' end of an RNA molecule. [GOC:jl]. eukaryotes defined as following: Organism or cells with a nucleus separated from the cytoplasm by a two membrance nuclear envelope and compartmentalization of function into distinct cytoplasmic organelles.. Escherichia coli defined as following: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.. organisms defined as following: A living entity.. nucleus defined as following: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). polyadenylate defined as following: A group of adenine ribonucleotides in which the phosphate residues of each adenine ribonucleotide act as bridges in forming diester linkages between the ribose moieties.. RNA defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. mRNA precursor defined as following: A primary RNA transcript synthesized from a DNA template in eukaryotic nuclei which is post-transcriptionally modified and spliced to produce a mature mRNA.. mitochondrial defined as following: The distribution of mitochondria, including the mitochondrial genome, into daughter cells after mitosis or meiosis, mediated by interactions between mitochondria and the cytoskeleton. [GOC:mcc, PMID:10873824, PMID:11389764]. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. Adenosine defined as following: A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter..", "label": "no"} {"id": "converted_1265", "sentence1": "Are there any animal models for Niemann-Pick C1 disease?", "sentence2": "Several animal models were used to analyze the impaired pathways. , We investigated components of the surfactant system in both NPC1 mutant mice and felines and in NPC2 mutant mice near the end of their expected life span. , Thus far, studies of NPC mice have been performed mainly to study the brain and neurodegeneration, because degeneration in the brain was known as the primary cause of death in NPC mice. , the NPC1(-/-) mouse is available serving as an appropriate animal model of the human disease,, o examine the onset and progression of neuropathological insults in NPC we have systematically examined the CNS of a mouse model of NPC1 (Npc1(-/-) mice) at different stages of the disease course., We have identified a point mutation in Npc1 that creates a novel mouse model (Npc1(nmf164)) of Niemann-Pick type C1 (NPC) disease, Niemann-Pick type C1-deficient mice, which accumulate intracellular free cholesterol. , hUCB-MSCs were transplanted into the hippocampus of NPC mice in the early asymptomatic stage., Niemann Pick type C1 mice, Three mouse models of glycosphingolipid storage diseases, namely Niemann-Pick type C1,, Npc1(-/-) mice, a well-established model of NPC pathology, murine model of this disease, the npc1 mouse,, NPC1 (Niemann-Pick type C1) knock-out mice, We have made transgenic mice which express the Npc1 protein exclusively in fibrillary astrocytes, using the glial fibrillary acidic protein (GFAP) promoter., homozygous affected (NPC1(-/-)) mice, heterozygous (NPC1(+/-)) mice, npc1(-/-) mice,, npc1(-/-) mouse model, A murine model of Niemann-Pick type C disease (NPC), the NPC1-deficient [NPC1 (-/-)] mouse, [SEP]Relations: Niemann-Pick disease type C has relations: disease_disease with Niemann-Pick disease, disease_disease with Niemann-Pick disease, disease_disease with Niemann-Pick disease, disease_disease with Niemann-Pick disease, disease_disease with Niemann-Pick disease, disease_disease with Niemann-Pick disease. central nervous system has relations: anatomy_protein_present with NISCH, anatomy_protein_present with NISCH, anatomy_protein_present with NIPAL3, anatomy_protein_present with NIPAL3. Definitions: point mutation defined as following: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.. NPC2 defined as following: Type C Niemann-Pick disease associated with a mutation in the gene NPC2, encoding Niemann-Pick C2 protein.. Npc1 defined as following: Type C Niemann-Pick disease associated with a mutation in the gene NPC1, encoding Niemann-Pick C1 protein.. GFAP defined as following: An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000.. NPC defined as following: A carcinoma that originates in the EPITHELIUM of the NASOPHARYNX and includes four subtypes: keratinizing squamous cell, non-keratinizing, basaloid squamous cell, and PAPILLARY ADENOCARCINOMA. It is most prevalent in Southeast Asian populations and is associated with EPSTEIN-BARR VIRUS INFECTIONS. Somatic mutations associated with this cancer have been identified in NPCR, BAP1, UBAP1, ERBB2, ERBB3, MLL2, PIK3CA, KRAS, NRAS, and ARID1A genes.. neurodegeneration defined as following: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.. Npc1 protein defined as following: A transmembrane intracellular lipid transporter that helps trafficking lipids, particularly cholesterol, from late endosome/lysosome to the ER and plasma membrane. It may also play a role in other cellular cholesterol homeostasis and is an endosomal entry receptor for filoviruses including EBOLAVIRUS. Mutations in the NPC1 are associated with type C NIEMANN-PICK DISEASE.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. promoter defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. Niemann-Pick type C disease defined as following: An autosomal recessive lipid storage disorder that is characterized by accumulation of CHOLESTEROL and SPHINGOMYELINS in cells of the VISCERA and the CENTRAL NERVOUS SYSTEM. Type C (or C1) and type D are allelic disorders caused by mutation of the NPC1 gene, which encodes a protein that mediates intracellular cholesterol transport from LYSOSOMES. Clinical signs include hepatosplenomegaly and chronic neurological symptoms. Type D is a variant in people with a Nova Scotia ancestry.. felines defined as following: The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801). transgenic mice defined as following: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. murine defined as following: Any of numerous species of small rodents belonging to the genus Mus and various related genera of the family Muridae.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown..", "label": "yes"} {"id": "converted_2009", "sentence1": "Can Pentraxin 3 predict outcomes of sepsis?", "sentence2": "As compared with low serum PTX3and sTWEAK cases, cirrhotic patients with high serum PTX3/sTWEAK levels a have higher probability of new severe infections, severe sepsis, septic shock, type 1 hepatorenal syndrome, in-hospital, and 3-month follow-up mortalities. , Neonates with high nPTX3 concentrations also have lowered APGAR scores, increased rate of respiratory distress syndrome, clinical sepsis, IVH, necrotizing enterocolitis and prolonged NICU stay., In terms of predicting the prognosis of sepsis with heart failure complications, the PTX3 value's area under ROC curve was larger than that of BNP (respectively 0. 844, 0. 472).CONCLUSION: The PTX3 is an objective biochemical marker in diagnosis of sepsis; it is helpful in assessment of severity and prognosis of sepsis; it also has a certain clinical value in the assessment of sepsis cardiovascular function damage., Severe Acinetobacter baumannii sepsis is associated with elevation of pentraxin 3., Together, these results suggest that elevation of PTX3 is associated with fulminant disease during A. baumannii sepsis., Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality., PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis., CONCLUSIONS: Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality. PTX3 correlates with severity of sepsis and with sepsis-associated coagulation/fibrinolysis dysfunction., Pentraxin 3 in patients with severe sepsis or shock: the ALBIOS trial., Pentraxin 3: an immune modulator of infection and useful marker for disease severity assessment in sepsis., Redox state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis., The prototypic long pentraxin, pentraxin 3, is an acute phase protein that is structurally related but distinct from C-reactive protein which has proven to correlate with the severity of bacterial infection in critically ill patients., Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients., Pentraxin 3 (PTX3) is associated with severe sepsis and fatal disease in emergency room patients with suspected infection: a prospective cohort study., In addition, high levels of PTX3 were associated with unfavorable outcome.CONCLUSIONS: The long pentraxin PTX3 is elevated in critically ill patients and correlates with severity of disease and infection., PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis., Redox state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis., Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality., Pentraxin 3 (PTX3) is associated with severe sepsis and fatal disease in emergency room patients with suspected infection: a prospective cohort study., The proteomic profile of circulating pentraxin 3 (PTX3) complex in sepsis demonstrates the interaction with azurocidin 1 and other components of neutrophil extracellular traps.[SEP]Relations: newborn respiratory distress syndrome has relations: disease_phenotype_positive with Sepsis, disease_phenotype_positive with Sepsis. Protein S human has relations: drug_drug with Seproxetine, drug_drug with Seproxetine, drug_drug with Octamoxin, drug_drug with Octamoxin, drug_drug with Desvenlafaxine, drug_drug with Desvenlafaxine. Congestive heart failure has relations: drug_effect with Pentostatin, drug_effect with Pentostatin. Definitions: C-reactive protein defined as following: A plasma protein that circulates in increased amounts during inflammation and after tissue damage. C-Reactive Protein measured by more sensitive methods often for coronary heart disease risk assessment is referred to as High Sensitivity C-Reactive Protein (hs-CRP).. infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. shock defined as following: A pathological condition manifested by failure to perfuse or oxygenate vital organs.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. Pentraxin 3 defined as following: This gene is involved in complement recognition of pathogens.. bacterial infection defined as following: Infections by bacteria, general or unspecified.. respiratory distress syndrome defined as following: A condition beginning in the first day of life that results from inadequate surfactant production, causing increased work of breathing and impaired gas exchange.. heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. septic shock defined as following: Sepsis associated with HYPOTENSION or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include but are not limited to LACTIC ACIDOSIS; OLIGURIA; or acute alteration in mental status.. critically ill defined as following: A disease or state in which death is possible or imminent..", "label": "yes"} {"id": "converted_3649", "sentence1": "Is SATB1 expressed in thymocytes?", "sentence2": "A thymocyte factor SATB1 suppresses transcription of stably integrated matrix-attachment region-linked reporter genes., SATB1 is a homeodomain protein and is predominantly expressed in thymocytes. , SATB1 is a cell-type specific nuclear protein that recruits chromatin-remodeling factors and regulates numerous genes during thymocyte differentiation., This was shown by fluorescence in situ hybridization on wild-type and Satb1-null thymocytes using in vivo SATB1-bound sequences as probes. , By contrast, in Satb1-null thymocytes, this site is marked by methylation at H3 Lys9., Regulation of SATB1 during thymocyte development by TCR signaling., In this study we show that special AT-rich binding protein 1 (SATB1), a T lineage-enriched chromatin organizer and regulator, is induced in response to TCR signaling during early thymocyte development, SATB1 expression profile coincides with T lineage commitment and upregulation of SATB1 correlates with positive selection of thymocytes. , We also demonstrate that GATA3, the key transcriptional regulator of αβ T cells positively regulates SATB1 expression in thymocytes suggesting an important role for SATB1 during T cell development., High level expression of the Xlr nuclear protein in immature thymocytes and colocalization with the matrix-associated region-binding SATB1 protein., A role for SATB1, a nuclear matrix association region-binding protein, in the development of CD8SP thymocytes and peripheral T lymphocytes., Because homozygous SATB1-null mice do not survive to adulthood due to non-thymus autonomous defects, mice were produced that were homozygous for a T cell-specific SATB1-antisense transgene and heterozygous for a SATB1-null allele., Thymic SATB1 protein was reduced significantly in these mice, and the major cellular phenotype observed was a significant reduction in the percentage of CD8SP T cells in thymus, spleen, and lymph nodes. , The reduction in thymic SATB1 does not lead to the variegated expression of CD8-negative single positive thymocytes seen upon deletion of several regulatory elements and suggested by others to reflect failure to activate the CD8 locus. [SEP]Relations: GATA3 has relations: anatomy_protein_present with thymus, anatomy_protein_present with thymus, bioprocess_protein with thymus development, bioprocess_protein with thymus development, bioprocess_protein with thymic T cell selection, bioprocess_protein with thymic T cell selection, protein_protein with CHAF1B, protein_protein with CHAF1B, bioprocess_protein with regulation of CD4-positive, alpha-beta T cell differentiation, bioprocess_protein with regulation of CD4-positive, alpha-beta T cell differentiation. Definitions: cellular defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. thymocytes defined as following: HEMATOPOIETIC PROGENITOR CELLS that have migrated to the THYMUS where they differentiate into T-LYMPHOCYTES. Thymocytes are classified into maturational stages based on the expression of CELL SURFACE ANTIGENS.. T cell defined as following: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.. TCR defined as following: The nucleotide-excision repair process that carries out preferential repair of DNA lesions on the actively transcribed strand of the DNA duplex. In addition, the transcription-coupled nucleotide-excision repair pathway is required for the recognition and repair of a small subset of lesions that are not recognized by the global genome nucleotide excision repair pathway. [PMID:10197977, PMID:11900249]. homeodomain protein defined as following: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).. probes defined as following: A device designed to reach into a location for manipulating or sensing.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. SATB1 defined as following: DNA-Binding Protein SATB1 (763 aa, ~86 kDa) is encoded by the human SATB1 gene. This protein binds DNA and may be involved in the regulation of transcription.. GATA3 defined as following: This gene plays a role in the modulation of transcription.. thymus defined as following: A plant genus of the family LAMIACEAE best known for the thyme spice added to foods..", "label": "yes"} {"id": "converted_3263", "sentence1": "Are astrocytes part of the blood brain barrier?", "sentence2": "The blood-brain barrier (BBB) is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation., The blood-brain barrier (BBB) consists of endothelial cells, astrocytes, and pericytes embedded in basal lamina (BL).[SEP]Relations: blood brain barrier has relations: anatomy_anatomy with cell layer, anatomy_anatomy with cell layer, anatomy_anatomy with glial blood brain barrier, anatomy_anatomy with glial blood brain barrier. Astrocytosis has relations: disease_phenotype_positive with photomyoclonus, diabetes mellitus, deafness, nephropathy, and cerebral dysfunction, disease_phenotype_positive with photomyoclonus, diabetes mellitus, deafness, nephropathy, and cerebral dysfunction, phenotype_phenotype with Abnormal astrocyte morphology, phenotype_phenotype with Abnormal astrocyte morphology, disease_phenotype_positive with motor neuron disease with dementia and ophthalmoplegia, disease_phenotype_positive with motor neuron disease with dementia and ophthalmoplegia. Definitions: pericytes defined as following: Unique slender cells with multiple processes extending along the capillary vessel axis and encircling the vascular wall, also called mural cells. Pericytes are imbedded in the BASEMENT MEMBRANE shared with the ENDOTHELIAL CELLS of the vessel. Pericytes are important in maintaining vessel integrity, angiogenesis, and vascular remodeling.. astrocytes defined as following: A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from \"star\" cells) are irregularly shaped with many long processes, including those with \"end feet\" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and \"reactive astrocytes\" (along with MICROGLIA) respond to injury.. basal lamina defined as following: A layer of extracellular matrix found beneath epithelial tissues. It is secreted by epithelial cells and comprised of proteoglycans, laminin and type IV collagen.. BL defined as following: A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.. endothelial cells defined as following: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer..", "label": "yes"} {"id": "converted_1513", "sentence1": "Is thrombophilia related to increased risk of miscarriage?", "sentence2": "Thrombophilia does hardly increase the risk of IUGR/PMPC or if so, it can be prevented by LMWH, for illustrative purposes, a patient presenting with combined thrombophilia--both genetic and acquired--will be discussed. This patient had suffered severe gestational complications that led to devastating obstetrical outcome, Thrombophilias have been implicated in complications related to ischemic placental disease including recurrent pregnancy loss, intrauterine fetal demise, preeclampsia, fetal growth restriction, placental abruption, and preterm delivery, Further information about the combined risk of aPC resistance and pregnancy is needed before guidance on the management of affected women can be formulated., Thrombotic risk during pregnancy and the puerperium is higher in asymptomatic women with than without thrombophilia, Further studies are required to assess the thrombotic risk in women with preeclampsia as well as early or late recurrent pregnancy loss., Risk of pregnancy-related venous thrombosis in carriers of severe inherited thrombophilia, In conclusion, homozygous carriers of factor V Leiden and, to a lesser extent, double heterozygous carriers of factor V Leiden and of the prothrombin mutation have an increased risk of venous thrombosis during pregnancy, particularly high during the postpartum period, Careful diagnosis, observation and monitoring can add significant benefit to LMWH therapy during pregnancy, Pregnancy in healthy women is accompanied by hypercoagulable changes that may interact with thrombophilia risk factors and threaten pregnancy., Fifty-three (13 %) women had antiphospholipid antibodies (lupus anticoagulant and/or anti-beta2-glycoprotein 1 antibodies) mainly associated with the risk of spontaneous abortion during the first trimester, thrombophilia was found to be considerably more common in women with pregnancy-associated complications in comparison with the general population, and most frequently in conjunction with venous thromboembolism during pregnancy and the postpartum period, When counseling white women with a history of preeclampsia, screening for thrombophilia can be useful for preconceptional counseling and pregnancy management., knowledge combined with the appropriate use of thromboprophylaxis and treatment in women who have objectively confirmed VTE continue to improve maternal and perinatal outcomes, The risk of having thrombophilia is doubled in men who have fathered pregnancies which ended in perinatal death as well as in the mothers of such pregnancies., The prevalence of thrombophilic variants is of possible public health significance for other morbidity; but perhaps not in relation to preeclampsia, This study suggests that thrombophilia \"mediates\" in lowering of cardiovascular risk factors in women with a history of preeclampsia[SEP]Relations: thrombophilia has relations: disease_disease with inherited thrombophilia, disease_disease with inherited thrombophilia, disease_phenotype_positive with Recurrent thrombophlebitis, disease_phenotype_positive with Recurrent thrombophlebitis, disease_phenotype_positive with Preeclampsia, disease_phenotype_positive with Preeclampsia, disease_phenotype_positive with Hypercoagulability, disease_phenotype_positive with Hypercoagulability, disease_phenotype_positive with Thromboembolism, disease_phenotype_positive with Thromboembolism. Definitions: variants defined as following: An alteration or difference from a norm or standard.. Thrombophilia defined as following: A disorder of HEMOSTASIS in which there is a tendency for the occurrence of THROMBOSIS.. preeclampsia defined as following: A complication of PREGNANCY, characterized by a complex of symptoms including maternal HYPERTENSION and PROTEINURIA with or without pathological EDEMA. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease.. aPC defined as following: A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.. venous thrombosis defined as following: The formation or presence of a blood clot (THROMBUS) within a vein.. venous thromboembolism defined as following: Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream.. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. factor V defined as following: Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Deficiency of factor V leads to Owren's disease.. thrombophilia defined as following: A disorder of HEMOSTASIS in which there is a tendency for the occurrence of THROMBOSIS..", "label": "yes"} {"id": "converted_2860", "sentence1": "Can CPX-351 be used for the treatment of tuberculosis?", "sentence2": "CPX-351 is a novel liposomal formulation of cytarabine and daunorubicin which has recently been FDA approved for treatment of acute myeloid leukemia (AML).[SEP]Relations: acute promyelocytic leukemia has relations: disease_protein with TBL1XR1, disease_protein with TBL1XR1, disease_protein with ITGAX, disease_protein with ITGAX. Daunorubicin has relations: drug_drug with Baricitinib, drug_drug with Baricitinib, drug_drug with Novobiocin, drug_drug with Novobiocin. Cytarabine has relations: drug_drug with Baricitinib, drug_drug with Baricitinib. Definitions: AML defined as following: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.. cytarabine defined as following: A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472). acute myeloid leukemia defined as following: This gene plays a role in transcriptional regulation and cytogenetic aberrations are associated with several leukemias.. daunorubicin defined as following: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.. tuberculosis defined as following: Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM TUBERCULOSIS..", "label": "no"} {"id": "converted_2897", "sentence1": "Is lucatumumab a polyclonal antibody?", "sentence2": "A phase 1 study of lucatumumab, a fully human anti-CD40 antagonist monoclonal antibody administered intravenously to patients with relapsed or refractory multiple myeloma., In this open-label, multicentre, phase 1 study a fully human anti-CD40 antagonist monoclonal antibody, lucatumumab, was evaluated in patients with relapsed/refractory multiple myeloma (MM).[SEP]Relations: Lucatumumab has relations: drug_drug with Ficlatuzumab, drug_drug with Ficlatuzumab, drug_drug with Ecromeximab, drug_drug with Ecromeximab, drug_drug with Daclizumab, drug_drug with Daclizumab, drug_drug with Xentuzumab, drug_drug with Xentuzumab, drug_drug with Olaratumab, drug_drug with Olaratumab. Definitions: lucatumumab defined as following: A fully human monoclonal antibody directed against the B-cell surface antigen CD40 with potential antineoplastic activity. Lucatumumab binds to and inhibits CD40, thereby inhibiting CD40 ligand-induced cell proliferation and triggering cell lysis via antibody-dependent cellular cytotoxicity (ADCC) in cells overexpressing CD40. CD40, an integral membrane protein found on the surface of B lymphocytes, is a member of the tumor necrosis factor receptor superfamily and is highly expressed in a number of B-cell malignancies.. MM defined as following: A unit of concentration (molarity unit) equal to one thousandth of a mole (10E-3 mole) of solute per one liter of solution.. human defined as following: Members of the species Homo sapiens..", "label": "no"} {"id": "converted_42", "sentence1": "Is irritable bowel syndrome more common in women with endometriosis?", "sentence2": "CONCLUSIONS: Comorbid pain syndromes, mood conditions and asthma are common in adolescents and young women with endometriosis., There are many etiologies of pelvic pain that present with symptoms resembling those of endometriosis-associated pelvic pain that are not diagnosable with laparoscopy, such as interstitial cystitis and irritable bowel syndrome., Often, such patients are labelled with irritable bowel syndrome. , Irritable bowel syndrome (IBS) is also common in this setting, and it was speculated that the visceral hypersensitivity associated with this condition might be amplifying the symptoms of endometriosis. , RESULTS: Compared with controls, patients with minimal to mild and moderate to severe endometriosis had a higher prevalence of symptoms consistent with IBS (0% vs 65% and 50%, respectively, p<0.001) with significantly lower mean pain thresholds (39.5 mm Hg (95% CI 36.0 to 43.0) vs 28.1 mm Hg (95% CI 24.5 to 31.6), p=0.001 and 28.8 mm Hg (95% CI 24.9 to 32.6), p=0.002) not explained by differences in rectal compliance. , Similarly, women with a history of irritable bowel syndrome were twice as likely to develop endometriosis [AOR=1.9, 95% CI (1.03-3.87)]., A weak association between reported family history of endometriosis and history of irritable bowel syndrome and the development of endometriosis was also observed. , Irritable bowel syndrome and chronic constipation in patients with endometriosis., Fifteen per cent of the patients with endometriosis also had IBS and 14% of the patients with endometriosis had functional constipation without IBS., CONCLUSION: In patients with endometriosis, 29% also had IBS or constipation. , Seventy-six women (21.4%) had previously been diagnosed with irritable bowel syndrome and 79% of them had endometriosis confirmed., Compared with controls, women with endometriosis had increased risks of abdominopelvic pain (OR 5.2 [95% CI: 4.7-5.7]), dysmenorrhoea (OR 8.1 [95% CI: 7.2-9.3]), menorrhagia (OR 4.0 [95% CI: 3.5-4.5]), subfertility (OR 8.2 [95% CI: 6.9-9.9]), dyspareunia and/or postcoital bleeding (OR 6.8 [95% CI: 5.7-8.2]), and ovarian cysts (OR 7.3 [95% CI: 5.7-9.4]), and of being diagnosed with irritable bowel syndrome (IBS) (OR 1.6 [95% CI: 1.3-1.8]) or pelvic inflammatory disease (OR 3.0 [95% CI: 2.5-3.6])., Endometriosis may coexist with or be misdiagnosed as pelvic inflammatory disease or IBS., RESULTS: Compared with the controls, women with endometriosis were 3.5 times more likely to have received a diagnosis of IBS (OR 3.5 [95% CI: 3.1-3.9]). Even after women had been diagnosed with endometriosis, they were still two and a half times more likely to receive a new diagnosis of IBS when compared with the controls (OR 2.5 [95% CI: 2.2-2.8])., CONCLUSIONS: Women with endometriosis are more likely to be diagnosed with IBS and PID than controls, even after a definitive diagnosis of endometriosis has been reached., In women, clinical studies suggest that functional pain syndromes such as irritable bowel syndrome, interstitial cystitis, and fibromyalgia, are co-morbid with endometriosis, chronic pelvic pain, and others diseases., In women, clinical studies suggest that pain syndromes such as irritable bowel syndrome and interstitial cystitis, which are associated with visceral hyperalgesia, are often comorbid with endometriosis and chronic pelvic pain. , Depression, anxiety, IBS, FM, CFS, and IC were more common in migraine with EM group than in controls., Intestinal endometriosis can mimic many gastrointestinal diseases, such as irritable bowel syndrome, inflammatory bowel disease, infections and neoplasms., Endometriosis is often associated with other painful conditions such as irritable bowel syndrome, interstitial cystitis and fibromyalgia. , CONCLUSIONS: Diagnosis of endometriosis should be considered in women with recurrent monthly abdominal pain and bowel symptoms, especially if accompanied by gynaecologic complaints, even because the significant symptoms overlap with the irritable bowel syndrome (IBS) and makes the differentiation extremely difficult., Intestinal endometriosis is typically asymptomatic; however, when symptoms occur, they can mimic those of irritable bowel syndrome., Similarly, women with a history of irritable bowel syndrome were twice as likely to develop endometriosis [AOR=1., Irritable bowel syndrome (IBS) is also common in this setting, and it was speculated that the visceral hypersensitivity associated with this condition might be amplifying the symptoms of endometriosis., Irritable bowel syndrome (IBS) is also common in this setting, and it was speculated that the visceral hypersensitivity associated with this condition might be amplifying the symptoms of endometriosis.[SEP]Relations: irritable bowel syndrome has relations: disease_disease with intestinal disease, disease_disease with intestinal disease, disease_disease with syndromic disease, disease_disease with syndromic disease, disease_protein with IL10, disease_protein with IL10, disease_protein with MAGI2, disease_protein with MAGI2. intestinal disease has relations: disease_disease with irritable bowel syndrome, disease_disease with irritable bowel syndrome. Definitions: Irritable bowel syndrome defined as following: Gastrointestinal symptoms characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause.. dysmenorrhoea defined as following: Painful menstruation.. PID defined as following: Phosphotyrosine binding (PTB) domains are 100-150 residue modules that commonly bind Asn-Pro-X-Tyr motifs. The PTB domains of the docking proteins Shc and IRS-1 require ligand phosphorylation on the tyrosine residue (NPXpY) for binding. More N-terminal sequences are also required for high affinity binding and conferring specificity. The peptide binds as a b-strand to an anti-parallel b-sheet, while the NPXpY motif makes a turn, positioning the pY for recognition by basic residues. The PTB domains of proteins such as X11, Dab, Fe65 and Numb apparently recognize NPXY or related peptide motifs, but are not dependent on ligand phosphorylation. In addition, the Numb PTB domain can bind an unrelated peptide that forms a helical turn.. abdominal pain defined as following: Sensation of discomfort, distress, or agony in the abdominal region.. pelvic inflammatory disease defined as following: A spectrum of inflammation involving the female upper genital tract and the supporting tissues. It is usually caused by an ascending infection of organisms from the endocervix. Infection may be confined to the uterus (ENDOMETRITIS), the FALLOPIAN TUBES; (SALPINGITIS); the ovaries (OOPHORITIS), the supporting ligaments (PARAMETRITIS), or may involve several of the above uterine appendages. Such inflammation can lead to functional impairment and infertility.. fibromyalgia defined as following: A common nonarticular rheumatic syndrome characterized by myalgia and multiple points of focal muscle tenderness to palpation (trigger points). Muscle pain is typically aggravated by inactivity or exposure to cold. This condition is often associated with general symptoms, such as sleep disturbances, fatigue, stiffness, HEADACHES, and occasionally DEPRESSION. There is significant overlap between fibromyalgia and the chronic fatigue syndrome (FATIGUE SYNDROME, CHRONIC). Fibromyalgia may arise as a primary or secondary disease process. It is most frequent in females aged 20 to 50 years. (From Adams et al., Principles of Neurology, 6th ed, p1494-95). CFS defined as following: A syndrome characterized by persistent or recurrent fatigue, diffuse musculoskeletal pain, sleep disturbances, and subjective cognitive impairment of 6 months duration or longer. Symptoms are not caused by ongoing exertion; are not relieved by rest; and result in a substantial reduction of previous levels of occupational, educational, social, or personal activities. Minor alterations of immune, neuroendocrine, and autonomic function may be associated with this syndrome. There is also considerable overlap between this condition and FIBROMYALGIA. (From Semin Neurol 1998;18(2):237-42; Ann Intern Med 1994 Dec 15;121(12): 953-9). FM defined as following: A unit of concentration (molarity unit) equal to one quadrillionth of a mole (10E-15 mole) of solute in one liter of solution.. migraine defined as following: A common, severe type of vascular headache often associated with increased sympathetic activity, resulting in nausea, vomiting, and light sensitivity.. neoplasms defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. menorrhagia defined as following: Excessive uterine bleeding during MENSTRUATION.. gastrointestinal diseases defined as following: Diseases in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.. anxiety defined as following: Persistent and disabling ANXIETY.. ovarian cysts defined as following: General term for CYSTS and cystic diseases of the OVARY.. asthma defined as following: A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).. endometriosis defined as following: A condition in which functional endometrial tissue is present outside the UTERUS. It is often confined to the PELVIS involving the OVARY, the ligaments, cul-de-sac, and the uterovesical peritoneum.. EM defined as following: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.. constipation defined as following: Infrequent or difficult evacuation of FECES. These symptoms are associated with a variety of causes, including low DIETARY FIBER intake, emotional or nervous disturbances, systemic and structural disorders, drug-induced aggravation, and infections.. chronic constipation defined as following: Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation. [ORCID:0000-0001-5208-3432]. irritable bowel syndrome defined as following: Gastrointestinal symptoms characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause..", "label": "yes"} {"id": "converted_3205", "sentence1": "Does RUNX2 inhibit astrocyte differentiation?", "sentence2": "The method was able to recapitulate experimentally validated cell-fate determinants, and validation of two predicted cell-fate determinants confirmed that overexpression of ESR1 and RUNX2 in mouse neural stem cells induces neuronal and astrocyte differentiation, respectively.[SEP]Relations: regulation of intracellular estrogen receptor signaling pathway has relations: bioprocess_protein with RUNX1, bioprocess_protein with RUNX1, bioprocess_protein with AXIN1, bioprocess_protein with AXIN1, bioprocess_protein with CARM1, bioprocess_protein with CARM1, bioprocess_protein with UBA5, bioprocess_protein with UBA5, bioprocess_protein with DDRGK1, bioprocess_protein with DDRGK1. Definitions: RUNX2 defined as following: Runt-related transcription factor 2 (521 aa, ~57 kDa) is encoded by the human RUNX2 gene. This protein plays a role in the regulation of both bone development and transcription.. ESR1 defined as following: Estrogen receptor (595 aa, ~66 kDa) is encoded by the human ESR1 gene. This protein plays a role in the regulation of estradiol-dependent gene transcription.. astrocyte defined as following: A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from \"star\" cells) are irregularly shaped with many long processes, including those with \"end feet\" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and \"reactive astrocytes\" (along with MICROGLIA) respond to injury..", "label": "no"} {"id": "converted_4535", "sentence1": "Is there a way to distinguish COVID-19 clinically from other respiratory illnesses, particularly influenza?", "sentence2": "Findings indicate that clinical symptoms alone would be insufficient to distinguish between coronavirus disease 2019 and other respiratory infections (eg, influenza) and/or to evaluate the effects of preventive interventions (eg, vaccinations)., Our reasoning highlights how challenging a balanced approach to a patient with fever and flu-like symptoms can be. At present, clinical workup of COVID-19 remains a hard task to accomplish., In our retrospective cohort study comparing the clinical presentation of COVID-19 and other respiratory viral infections, we found that anosmia and dysgeusia were symptoms independently associated with COVID-19 and can be important differentiating symptoms in patients presenting with acute respiratory illness. On the other hand, laboratory abnormalities and radiological findings were not statistically different between the two groups., COVID-19 has a similar pattern of infection, clinical symptoms, and chest imaging findings to influenza pneumonia., Here, we hypothesize the order of symptom occurrence could help patients and medical professionals more quickly distinguish COVID-19 from other respiratory diseases, yet such essential information is largely unavailable, It is difficult to distinguish coronavirus disease-2019 (COVID-19) from other viral respiratory tract infections owing to the similarities in clinical and radiological findings.[SEP]Relations: viral respiratory tract infection has relations: disease_disease with influenza, disease_disease with influenza, disease_disease with respiratory syncytial virus infectious disease, disease_disease with respiratory syncytial virus infectious disease. Respiratory tract infection has relations: phenotype_phenotype with Acute infectious pneumonia, phenotype_phenotype with Acute infectious pneumonia, disease_phenotype_positive with ALG12-CDG, disease_phenotype_positive with ALG12-CDG. Pneumonia has relations: disease_phenotype_positive with adult acute respiratory distress syndrome, disease_phenotype_positive with adult acute respiratory distress syndrome. Definitions: coronavirus defined as following: Virus diseases caused by the CORONAVIRUS genus. Some specifics include transmissible enteritis of turkeys (ENTERITIS, TRANSMISSIBLE, OF TURKEYS); FELINE INFECTIOUS PERITONITIS; and transmissible gastroenteritis of swine (GASTROENTERITIS, TRANSMISSIBLE, OF SWINE).. dysgeusia defined as following: A condition characterized by alterations of the sense of taste which may range from mild to severe, including gross distortions of taste quality.. viral respiratory tract infections defined as following: A respiratory tract infection caused by a virus. Viruses represent the most common causes of upper and lower respiratory tract infections and include rhinoviruses, influenza viruses, parainfluenza viruses, and respiratory syncytial virus.. infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. pneumonia defined as following: Infection of the lung often accompanied by inflammation.. anosmia defined as following: Inability to smell.. respiratory diseases defined as following: Diseases involving the RESPIRATORY SYSTEM.. respiratory infections defined as following: Invasion of the host RESPIRATORY SYSTEM by microorganisms, usually leading to pathological processes or diseases..", "label": "no"} {"id": "converted_3291", "sentence1": "Is traditional Chinese medicine associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment?", "sentence2": "Traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment, Using TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy., Traditional Chinese medicine is associated with a decreased risk of heart failure in breast cancer patients receiving doxorubicin treatment., CONCLUSION\n\nUsing TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy., CONCLUSION\nUsing TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy., CONCLUSION: Using TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy., Using TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy.[SEP]Relations: Congestive heart failure has relations: drug_effect with Doxorubicin, drug_effect with Doxorubicin, drug_effect with Doxazosin, drug_effect with Doxazosin, drug_effect with Celecoxib, drug_effect with Celecoxib, drug_effect with Ofloxacin, drug_effect with Ofloxacin, drug_effect with Rofecoxib, drug_effect with Rofecoxib. Definitions: breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. CHF defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs..", "label": "yes"} {"id": "converted_163", "sentence1": "Does MicroRNA-21 (miR-21) contribute to cardiovascular disease?", "sentence2": "The synergistic effect of miR-21 and miR-1 were functionally validated for their significant influences on myocardial apoptosis, cardiac hypertrophy and fibrosis., Taken together, we found a novel reciprocal loop between miR-21 and TGFβRIII in cardiac fibrosis caused by myocardial infarction in mice, and targeting this pathway could be a new strategy for the prevention and treatment of myocardial remodeling., It is still controversial whether microRNA-21 (miR-21) participates in the process of cardiac fibrosis., In mice, myocardial miR-21 overexpression is related to cardiac fibrosis elicited by pressure overload. , The myocardial and plasma levels of miR-21 were significantly higher in the AS patients compared with the controls and correlated directly with the echocardiographic mean transvalvular gradients., Our results support the role of miR-21 as a regulator of the fibrotic process that occurs in response to pressure overload in AS patients and underscore the value of circulating miR-21 as a biomarker for myocardial fibrosis., Ad-miR-21 improves LV remodeling and decreases the apoptosis of myocardial cells, suggesting the possible mechanism by which Ad-miR-21 functions in protecting against I/R injury., In the Ad-miR-21 group, LV dimensions, myocardial infarct size, LV/BW, collagen type Ⅰ, type Ⅲ and PCNA positive cells all significantly decreased compared with the Ad-GFP group., While miR-21, -133, -150, -195, and -214 regulate cardiomyocyte hypertrophy, miR-1/-133 and miR-208 have been elucidated to influence myocardial contractile function. In addition, miR-21, -24, -133, -210, -494, and -499 appear to protect myocytes against I/R-induced apoptosis, whereas miR-1, -29, -199a, and -320 promote apoptosis. Myocardial fibrosis can be regulated by the miR-29 family and miR-21., The small regulatory RNA microRNA-21 (miR-21) plays a crucial role in a plethora of biological functions and diseases including development, cancer, cardiovascular diseases and inflammation., During recent years, additional roles of miR-21 in cardiovascular and pulmonary diseases, including cardiac and pulmonary fibrosis as well as myocardial infarction have been described., On the other hand, miR-21, miR-199a, miR-210, and miR-494 have been proven critical for the myocytes' adaptation and survival during hypoxia/ischemia. , Studies have shown that several miRs, including miR-1, miR-133, miR-21, miR-126, miR-320, miR-92a, and miR-199a, are regulated after preconditioning and play an active role in protecting the heart against ischemia/reperfusion injury., Studies using various in vivo, ex vivo, and in vitro models have suggested the possible involvement of miR-1, miR-21, miR-29, miR-92a, miR-133, miR-199a, and miR-320 in ischemia-reperfusion injury and/or remodeling after myocardial infarction., MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system. Recent studies have revealed that its expression is deregulated in heart and vasculature under cardiovascular disease conditions such as proliferative vascular disease, cardiac hypertrophy and heart failure, and ischemic heart disease. miR-21 is found to play important roles in vascular smooth muscle cell proliferation and apoptosis, cardiac cell growth and death, and cardiac fibroblast functions. Accordingly, miR-21 is proven to be involved in the pathogenesis of the above-mentioned cardiovascular diseases as demonstrated by both loss-of-function and gain-of-function approaches., miR-21 might be a novel therapeutic target in cardiovascular diseases., This review article summarizes the research progress regarding the roles of miR-21 in cardiovascular disease., Remarkably, miR-21 was one of most upregulated miRNAs in hearts after IP. In vivo, IP-mediated cardiac protection against ischaemia/reperfusion injury was inhibited by knockdown of cardiac miR-21. In cultured cardiac myocytes, we identified that miR-21 also had a protective effect on hypoxia/reoxygenation-induced cell apoptosis that was associated with its target gene, programmed cell death 4. The protective effect of miR-21 on cardiac cell apoptosis was further confirmed in rat hearts after ischaemia/reperfusion injury in vivo., Lately, some highlight articles revealed that the altered expression of miRNAs such as miR-1, miR-133, miR-21, miR-208 etc in hearts also contributed to cardiovascular diseases, such as heart ischemia, cardiac hypertrophy, and arrhythmias., Remarkably, miR-21 expression was significantly down-regulated in infarcted areas, but was up-regulated in border areas. The down-regulation of miR-21 in the infarcted areas was inhibited by ischemic preconditioning, a known cardiac protective method. Overexpression of miR-21 via adenovirus expressing miR-21 (Ad-miR-21) decreased myocardial infarct size by 29% at 24 h and decreased the dimension of left ventricles at 2 weeks after AMI. Using both gain-of-function and loss-of-function approaches in cultured cardiac myocytes, we identified that miR-21 had a protective effect on ischemia-induced cell apoptosis that was associated with its target gene programmed cell death 4 and activator protein 1 pathway. The protective effect of miR-21 against ischemia-induced cardiac myocyte damage was further confirmed in vivo by decreased cell apoptosis in the border and infarcted areas of the infarcted rat hearts after treatment with Ad-miR-21. The results suggest that miRNAs such as miR-21 may play critical roles in the early phase of AMI., The results suggest that miR-21 is sensitive to H(2)O(2) stimulation. miR-21 participates in H(2)O(2)-mediated gene regulation and functional modulation in cardiac myocytes. miR-21 might play an essential role in heart diseases related to ROS such as cardiac hypertrophy, heart failure, myocardial infarction, and myocardial ischemia/reperfusion injury., MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts, Myocardial and circulating levels of microRNA-21 reflect left ventricular fibrosis in aortic stenosis patients, MicroRNA 21 inhibits left ventricular remodeling in the early phase of rat model with ischemia-reperfusion injury by suppressing cell apoptosis, MicroRNA-21 protects against the H(2)O(2)-induced injury on cardiac myocytes via its target gene PDCD4, MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system., MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts., MicroRNA-21 (miR-21) is a highly expressed microRNA (miRNA) in cardiovascular system, miR-21 might be a novel therapeutic target in cardiovascular diseases, MicroRNA-21 as therapeutic target in cancer and cardiovascular disease., These findings reveal that microRNAs can contribute to myocardial disease by an effect in cardiac fibroblasts., Our results validate miR-21 as a disease target in heart failure and establish the therapeutic efficacy of microRNA therapeutic intervention in a cardiovascular disease setting.[SEP]Relations: cardiac muscle hypertrophy has relations: bioprocess_protein with MIR195, bioprocess_protein with MIR195, bioprocess_protein with MIR15B, bioprocess_protein with MIR15B. myocardial infarction has relations: disease_protein with MIR145, disease_protein with MIR145, disease_protein with MIR145, disease_protein with MIR145, disease_protein with MIR145, disease_protein with MIR145. Definitions: myocardial cells defined as following: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. miR-21 defined as following: This gene is involved in the regulation of gene expression and plays an oncogenic role in hepatocellular, breast, esophageal, gastric, pancreatic, prostatic and squamous cell carcinomas, glioblastoma and glioma.. myocardial infarct defined as following: NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).. cardiac cell defined as following: any of the cells which comprise the heart, including fibroblasts and cardiac myocytes; these cells can function to conduct electricity, support, and contract the heart.. ischemic heart disease defined as following: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).. IP defined as following: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.. heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. myocardial disease defined as following: A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).. Myocardial defined as following: Of or pertaining to the myocardium.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. ischemia-reperfusion injury defined as following: Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA.. MAP kinase defined as following: A superfamily of PROTEIN SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).. myocytes defined as following: Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal (MUSCLE FIBERS, SKELETAL), cardiac (MYOCYTES, CARDIAC), and smooth (MYOCYTES, SMOOTH MUSCLE). They are derived from embryonic (precursor) muscle cells called MYOBLASTS.. cancer defined as following: A malignant tumor at the original site of growth.. arrhythmias defined as following: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.. PDCD4 defined as following: Programmed cell death protein 4 (469 aa, ~52 kDa) is encoded by the human PDCD4 gene. This protein may be involved in the regulation of both apoptosis and translation.. aortic stenosis defined as following: A pathological constriction that can occur above (supravalvular stenosis), below (subvalvular stenosis), or at the AORTIC VALVE. It is characterized by restricted outflow from the LEFT VENTRICLE into the AORTA.. death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. fibrosis defined as following: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.. microRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. cardiac hypertrophy defined as following: Enlargement of the HEART due to chamber HYPERTROPHY, an increase in wall thickness without an increase in the number of cells (MYOCYTES, CARDIAC). It is the result of increase in myocyte size, mitochondrial and myofibrillar mass, as well as changes in extracellular matrix.. cardiovascular defined as following: The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body.. ROS defined as following: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.. AMI defined as following: MYOCARDIAL INFARCTION in which the anterior wall of the heart is involved. Anterior wall myocardial infarction is often caused by occlusion of the left anterior descending coronary artery. It can be categorized as anteroseptal or anterolateral wall myocardial infarction.. Myocardial fibrosis defined as following: The accumulation of fibrotic tissue in the myocardium. This may result from chronic hypertension, myocardial infarction or cardiomyopathy and eventually lead to heart failure..", "label": "yes"} {"id": "converted_2483", "sentence1": "Are the human bombesin receptors, GRPR and NMBR, frequently overexpressed G-protein-coupled-receptors by lung-cancers?", "sentence2": "Members of the gastrin-releasing peptide (GRP) family and its analogs bombesin (BBN) have been implicated in the biology of several human cancers including prostate, breast, colon and lung., All 3 bombesin receptor subtypes (GRPR, NMBR, and BRS-3) were present on pulmonary and intestinal carcinoids by immunohistochemistry, There is increased interest in the Bn-receptor family because they are frequently over/ectopically expressed by tumors and thus useful as targets for imaging or receptor-targeted-cytotoxicity. , ML-18 is a non-peptide bombesin receptor subtype-3 antagonist which inhibits lung cancer growth., Gastrin-releasing peptide (GRP), a member of the bombesin family of peptides, has been shown to have mitogenic activity in small cell lung carcinoma (SCLC), and to be produced by SCLC in an autocrine fashion.[SEP]Relations: small cell lung carcinoma has relations: disease_protein with GRM8, disease_protein with GRM8, disease_protein with GRIK3, disease_protein with GRIK3, disease_protein with NPPA, disease_protein with NPPA, disease_protein with NDRG1, disease_protein with NDRG1, disease_protein with EGFR, disease_protein with EGFR. Definitions: NMBR defined as following: Neuromedin-B receptor (390 aa, ~43 kDa) is encoded by the human NMBR gene. This protein is involved in both peptide hormone binding and G protein-coupled receptor signaling.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. human defined as following: Members of the species Homo sapiens.. breast defined as following: In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. SCLC defined as following: A form of highly malignant lung cancer that is composed of small ovoid cells (SMALL CELL CARCINOMA).. GRP defined as following: Neuropeptide and gut hormone that helps regulate GASTRIC ACID secretion and motor function. Once released from nerves in the antrum of the STOMACH, the neuropeptide stimulates release of GASTRIN from the GASTRIN-SECRETING CELLS.. GRPR defined as following: Gastrin-releasing peptide receptor (384 aa, ~43 kDa) is encoded by the human GRPR gene. This protein plays a role in the mediation of gastrin-dependent signaling.. gastrin-releasing peptide defined as following: This gene plays a role in the regulation of several gastrointestinal and central nervous system functions..", "label": "yes"} {"id": "converted_3670", "sentence1": "Is there a role for TET proteins in invariant natural killer T cells (iNKT) cell fate?", "sentence2": "TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells., We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4+CD8+ double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK. Transfer of purified Tet2-Tet3 DKO iNKT cells into immunocompetent recipient mice resulted in an uncontrolled expansion that was dependent on the nonclassical major histocompatibility complex (MHC) protein CD1d, which presents lipid antigens to iNKT cells. Our data indicate that TET proteins regulate iNKT cell fate by ensuring their proper development and maturation and by suppressing aberrant proliferation mediated by the T cell antigen receptor (TCR)., TET proteins regulate the lineage specification and TCR-mediated expansion of iNKT cells .[SEP]Relations: T cell receptor complex has relations: cellcomp_protein with TRAT1, cellcomp_protein with TRAT1, cellcomp_protein with SYK, cellcomp_protein with SYK, cellcomp_protein with TRGJ2, cellcomp_protein with TRGJ2, cellcomp_protein with TRGV11, cellcomp_protein with TRGV11, cellcomp_protein with TRGC1, cellcomp_protein with TRGC1. Definitions: T cell antigen receptor defined as following: Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (CD3 COMPLEX). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.. TCR defined as following: The nucleotide-excision repair process that carries out preferential repair of DNA lesions on the actively transcribed strand of the DNA duplex. In addition, the transcription-coupled nucleotide-excision repair pathway is required for the recognition and repair of a small subset of lesions that are not recognized by the global genome nucleotide excision repair pathway. [PMID:10197977, PMID:11900249]. Tet3 defined as following: Methylcytosine dioxygenase TET3 (1660 aa, ~179 kDa) is encoded by the human TET3 gene. This protein plays a role in oxidative demethylation of DNA.. Tet2 defined as following: Methylcytosine dioxygenase TET2 (2002 aa, ~224 kDa) is encoded by the human TET2 gene. This protein is involved in methylcytosine oxidation.. iNKT cells defined as following: A natural killer T-cell subtype bearing an invariant T-cell receptor. Invariant natural killer T-cells recognize a small variety of glycolipid antigens presented in the context of CD1d. These cells play a regulatory role during an immune response by producing cytokines.. T-bet defined as following: Human TBX21 wild-type allele is located in the vicinity of 17q21.32 and is approximately 13 kb in length. This allele, which encodes T-box transcription factor TBX21 protein, plays a role in the transcriptional regulation of interferon-gamma. Genetic variation is associated with susceptibility to asthma with nasal polyps and aspirin intolerance.. CD1d defined as following: Antigen-presenting glycoprotein CD1d (335 aa, ~38 kDa) is encoded by the human CD1D gene. This protein is involved in lipid antigen presentation.. ThPOK defined as following: Human ZBTB7B wild-type allele is located in the vicinity of 1q21.3 and is approximately 16 kb in length. This allele, which encodes zinc finger and BTB domain-containing protein 7B, is involved in the repression of type I collagen gene expression and the promotion of CD4-positive T-cell differentiation.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. invariant natural killer T cells defined as following: A natural killer T-cell subtype bearing an invariant T-cell receptor. Invariant natural killer T-cells recognize a small variety of glycolipid antigens presented in the context of CD1d. These cells play a regulatory role during an immune response by producing cytokines..", "label": "yes"} {"id": "converted_2877", "sentence1": "Can enasidenib be used for the treatment of acute myeloid leukemia?", "sentence2": "In August 2017, the United States Federal Drug Administration (FDA) approved enasidenib (Idhifa, Celgene/Agios) for adults with relapsed and refractory acute myelogenous leukemia (AML) with an IDH2 mutation. [SEP]Relations: acute promyelocytic leukemia has relations: disease_disease with bilineal acute myeloid leukemia, disease_disease with bilineal acute myeloid leukemia, disease_disease with acute myeloid leukemia with recurrent genetic anomaly, disease_disease with acute myeloid leukemia with recurrent genetic anomaly, disease_protein with KIT, disease_protein with KIT, disease_protein with CEBPA, disease_protein with CEBPA, disease_protein with ITGAM, disease_protein with ITGAM. Definitions: AML defined as following: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.. IDH2 defined as following: This gene plays a role in intermediary metabolism.. acute myeloid leukemia defined as following: This gene plays a role in transcriptional regulation and cytogenetic aberrations are associated with several leukemias..", "label": "yes"} {"id": "converted_4355", "sentence1": "Is Mycobacterium abscessus a human pathogen?", "sentence2": "Mycobacterium abscessus is unique in terms of its high morbidity and treatment failure rates, Mycobacterium abscessus has emerged as a successful pathogen owing to its intrinsic drug resistance. , Mycobacterium abscessus lung disease is difficult to treat due to intrinsic drug resistance and the persistence of drug-tolerant bacteria., Mycobacterium abscessus has been recognised as a dreadful respiratory pathogen among the non-tuberculous mycobacteria (NTM) because of misdiagnosis, prolonged therapy with poor treatment outcomes and a high cost. [SEP]Relations: Mycobacterium abscessus abscessus infection has relations: phenotype_phenotype with Opportunistic bacterial infection, phenotype_phenotype with Opportunistic bacterial infection, disease_phenotype_positive with pulmonary non-tuberculous mycobacterial infection, disease_phenotype_positive with pulmonary non-tuberculous mycobacterial infection. Nontuberculous mycobacterial pulmonary infection has relations: phenotype_phenotype with Opportunistic bacterial infection, phenotype_phenotype with Opportunistic bacterial infection. Definitions: Mycobacterium abscessus defined as following: A species of aerobic, Gram positive, rod shaped bacteria assigned to the phylum Actinobacteria. This species is acid-fast, nonmotile, does not reduce nitrate, is amidase, urease and nicotinamidase positive and benzamidase, isonicotinamidase, succinamidase and acetamidase negative. M. abscessus is a rapidly growing mycobacterium found in water, soil and dust, and can cause a variety of serious infections of the skin, soft tissues and lungs, especially in persons with chronic lung diseases.. NTM defined as following: So-called atypical species of the genus MYCOBACTERIUM that do not cause tuberculosis. They are also called tuberculoid bacilli, i.e.: M. abscessus, M. buruli, M. chelonae, M. duvalii, M. flavescens, M. fortuitum, M. gilvum, M. gordonae, M. intracellulare (see MYCOBACTERIUM AVIUM COMPLEX;), M. kansasii, M. marinum, M. obuense, M. scrofulaceum, M. szulgai, M. terrae, M. ulcerans, M. xenopi..", "label": "yes"} {"id": "converted_2868", "sentence1": "Is pazopanib an effective treatment of glioblastoma?", "sentence2": "RESULTS: The six-month progression-free survival (PFS) rates in phase II (n = 41) were 0% and 15% in the PTEN/EGFRvIII-positive and PTEN/EGFRvIII-negative cohorts, respectively, leading to early termination. , Single-agent pazopanib did not prolong PFS in this patient population but showed in situ biological activity as demonstrated by radiographic responses.[SEP]Definitions: glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO). pazopanib defined as following: A small molecule inhibitor of multiple protein tyrosine kinases with potential antineoplastic activity. Pazopanib selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3, c-kit and platelet derived growth factor receptor (PDGF-R), which may result in inhibition of angiogenesis in tumors in which these receptors are upregulated..", "label": "no"} {"id": "converted_2423", "sentence1": "Is Solanezumab effective for Alzheimer's Disease?", "sentence2": "An analysis of publicly available data from the Phase II studies for bapineuzumab and solanezumab indicates that neither compound produced compelling evidence of drug-like behavior that would justify their progression into pivotal trials. , Notably, a recent study of solanezumab, an amyloid β monoclonal antibody, raises hope for the further therapeutic potential of immunotherapy, not only in Alzheimer's disease, but also for other neurodegenerative disorders, including Parkinson's disease. , For example, Eli Lilly announced a major change to its closely watched clinical trial for the Alzheimer's drug solanezumab which failed to reach statistical significance. , Areas covered: This contradiction prompted us to review all study phases of Intravenous Immunoglobulin (IVIG), Bapineuzumab, Solanezumab, Avagacestat and Dimebolin to shed more light on these recent failures. , Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing. Subsequent analysis of pooled data from both phase III trials with solanezumab showed a reduction in cognitive decline in patients with mild AD., Secondary analyses of EXPEDITION studies suggested a smaller functional effect of solanezumab relative to cognition. An increasing effect of solanezumab over 18 months was shown for cognition and function., RESULTS: In the mild AD population, less cognitive and functional decline was observed with solanezumab (n = 659) versus placebo (n = 663), measured by Alzheimer's Disease Assessment Scale Cognitive subscale, Mini-Mental State Examination, and Alzheimer's Disease Cooperative Study-Activities of Daily Living functional scale Instrumental ADLs. , The promising results obtained with aducanumab and solanezumab against Alzheimer's disease (AD) strengthen the vaccine approach to prevent AD, despite of the many clinical setbacks. , CONCLUSIONS: Solanezumab, a humanized monoclonal antibody that binds amyloid, failed to improve cognition or functional ability. , Results from phase III clinical trials in mild-to-moderate Alzheimer's disease (AD) patients with two monoclonal antibodies bapineuzumab and solanezumab and intravenous immunoglobulin have been disappointing.[SEP]Relations: Solanezumab has relations: drug_drug with Adalimumab, drug_drug with Adalimumab, drug_drug with Eldelumab, drug_drug with Eldelumab, drug_drug with Idarucizumab, drug_drug with Idarucizumab, drug_drug with Alemtuzumab, drug_drug with Alemtuzumab, drug_drug with Refanezumab, drug_drug with Refanezumab. Definitions: neurodegenerative disorders defined as following: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.. monoclonal antibodies defined as following: Antibodies produced by a single clone of cells.. amyloid defined as following: A family of apolipoproteins that are associated with high-density lipoprotein particles in the serum. These proteins may play a role in both the acute-phase of inflammation and in cholesterol transport.. Bapineuzumab defined as following: A humanized monoclonal antibody (IgG1) raised against amyloid beta peptides with Alzheimer disease treatment application. Bapineuzumab recognizes and binds the N-terminal amino acids 1-5 of the amyloid beta peptide, and may be used in a passive immunotherapy treatment.. Solanezumab defined as following: A humanized monoclonal antibody (IgG1) raised against amyloid beta peptides with Alzheimer disease treatment application. Solanezumab recognizes and binds the middle amino acid residues 16-24 of the amyloid beta peptide and may be used in a passive immunotherapy treatment.. Alzheimer's Disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. cognitive decline defined as following: Loss of previously present mental abilities, generally in adults. [HPO:probinson]. Parkinson's disease defined as following: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75). Intravenous Immunoglobulin defined as following: Immunoglobulin preparations used in intravenous infusion, containing primarily IMMUNOGLOBULIN G. They are used to treat a variety of diseases associated with decreased or abnormal immunoglobulin levels including pediatric AIDS; primary HYPERGAMMAGLOBULINEMIA; SCID; CYTOMEGALOVIRUS infections in transplant recipients, LYMPHOCYTIC LEUKEMIA, CHRONIC; Kawasaki syndrome, infection in neonates, and IDIOPATHIC THROMBOCYTOPENIC PURPURA.. humanized monoclonal antibody defined as following: Antibodies from non-human species whose protein sequences have been modified to make them nearly identical with human antibodies. If the constant region and part of the variable region are replaced, they are called humanized. If only the constant region is modified they are called chimeric. INN names for humanized antibodies end in -zumab..", "label": "no"} {"id": "converted_2210", "sentence1": "Is dupilumab an antibody targeting the IL-1 receptor?", "sentence2": "Atopic dermatitis (AD) is characterized by type 2 helper T (Th2) cell-driven inflammation. Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor α subunit that blocks the signaling of IL-4 and IL-13, both key cytokines in Th2-mediated pathways., Dupilumab, a humanized monoclonal antibody to the interteukin-4R is the first antibody (i.e. 'biological') with published efficacy shown in controlled prospective studies in atopic dermatitis. , Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis., Best evidence of the clinical efficacy of novel immunologic approaches using biological agents in patients with AD is available for the anti-IL-4 receptor α-chain antibody dupilumab, but a number of studies are currently ongoing with other specific antagonists to immune system players., Dupilumab, a fully human anti-interleukin-4 receptor α monoclonal antibody, inhibits interleukin-4 and interleukin-13 signalling, key drivers of type-2-mediated inflammation. , Dupilumab was also introduced as a possible treatment for patients with severe pemphigus. It can directly inhibit IL-4 by targeting IL-4 α-chain receptor., We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor[SEP]Relations: Dupilumab has relations: drug_protein with IL4R, drug_protein with IL4R, drug_drug with Avelumab, drug_drug with Avelumab, drug_drug with IGN311, drug_drug with IGN311, drug_drug with Varlilumab, drug_drug with Varlilumab, drug_drug with Olaratumab, drug_drug with Olaratumab. Definitions: IL-4 defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine interleukin-4 (IL-4). Produced primarily by activated T-cells, IL-4 binds to and activates its cell-surface receptor, stimulating the proliferation and differentiation of activated B-cells and enhancing their ability to present antigens to T-cells. As a potential immunotherapeutic agent, recombinant IL-4 also augments the effects of other cytokines on dendritic cells (DC), cytotoxic T lymphocytes (CTL), and tumor-infiltrating lymphocytes (TIL). Check for \"https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/C589\" active clinical trials using this agent. (\"http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C589\" NCI Thesaurus). interleukin-4 receptor defined as following: Receptors present on a wide variety of hematopoietic and non-hematopoietic cell types that are specific for INTERLEUKIN-4. They are involved in signaling a variety of immunological responses related to allergic INFLAMMATION including the differentiation of TH2 CELLS and the regulation of IMMUNOGLOBULIN E production. Two subtypes of receptors exist and are referred to as the TYPE I INTERLEUKIN-4 RECEPTOR and the TYPE II INTERLEUKIN-4 RECEPTOR. Each receptor subtype is defined by its unique subunit composition.. alpha subunit defined as following: The alpha chain of pituitary glycoprotein hormones (THYROTROPIN; FOLLICLE STIMULATING HORMONE; LUTEINIZING HORMONE) and the placental CHORIONIC GONADOTROPIN. Within a species, the alpha subunits of these four hormones are identical; the distinct functional characteristics of these glycoprotein hormones are determined by the unique beta subunits. Both subunits, the non-covalently bound heterodimers, are required for full biologic activity.. interleukin-13 defined as following: Interleukin-13 (146 aa, ~16 kDa) is encoded by the human IL13 gene. This protein plays a role in the negative regulation of cytokine production and the positive regulation of B-cell proliferation.. human defined as following: Members of the species Homo sapiens.. interleukin-4 receptor alpha defined as following: Interleukin-4 receptor subunit alpha (825 aa, ~90 kDa) is encoded by the human IL4R gene. This protein plays a role in both interleukin-4 signaling and immunoglobulin E production.. Dupilumab defined as following: A recombinant human monoclonal immunoglobulin G4 (IgG4) antibody directed against the alpha chain of the interleukin-4 receptor (IL-4R alpha) with potential immunomodulatory activities. Upon injection, dupilumab selectively binds to the IL-4R alpha chain. This disrupts IL-4/IL-13 signaling and prevents the activation of downstream pathways that mediate type 2 inflammation and may potentially inhibit tumor cell proliferation, survival, and metastasis. IL-4 and IL-13 receptors are present on the surface of numerous cells involved in the pathophysiology of type-2 helper T-cell (Th2) allergic responses, including B-lymphocytes, eosinophils, dendritic cells (DCs), monocytes, macrophages, basophils, keratinocytes, bronchial epithelial cells, endothelial cells, fibroblasts, and airway smooth muscle cells. Additionally, both IL-4 and IL-13 receptors are overexpressed in a variety of cancers and IL-4 and IL-13 and may serve as biomarkers for cancer aggressiveness. IL-4 and IL-13 are thought to be key regulatory cytokines in the tumor microenvironment (TME) and may play a role in the activation of tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) that mediate tumor cell survival.. antibody defined as following: An immunoglobulin complex that is secreted into extracellular space and found in mucosal areas or other tissues or circulating in the blood or lymph. In its canonical form, a circulating immunoglobulin complex is composed of two identical heavy chains and two identical light chains, held together by disulfide bonds. Some forms of are polymers of the basic structure and contain additional components such as J-chain and the secretory component. [GOC:add, ISBN:0781735149]. Atopic dermatitis defined as following: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed).. atopic dermatitis defined as following: A chronic inflammatory genetically determined disease of the skin marked by increased ability to form reagin (IgE), with increased susceptibility to allergic rhinitis and asthma, and hereditary disposition to a lowered threshold for pruritus. It is manifested by lichenification, excoriation, and crusting, mainly on the flexural surfaces of the elbow and knee. In infants it is known as infantile eczema.. monoclonal antibody defined as following: A humanized monoclonal antibody directed against parathyroid hormone-related protein (PTH-rP). As a poly-hormone with diverse biological roles, PTH-rP is expressed by normal tissues, acting in local tissue environments in a variety of ways; it is commonly overexpressed by breast, prostate, and other cancers, acting systemically by promoting bone resorption, inhibiting calcium excretion from the kidney, inducing hypercalcemia, and possibly playing a role in the formation of bony metastases. By blocking the effects of PTH-rP on calcium metabolism, monoclonal antibody CAL may inhibit cancer-related hypercalcemia. (NCI04). IL-1 receptor defined as following: Cell surface receptors that are specific for INTERLEUKIN-1. Included under this heading are signaling receptors, non-signaling receptors and accessory proteins required for receptor signaling. Signaling from interleukin-1 receptors occurs via interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88..", "label": "no"} {"id": "converted_550", "sentence1": "Does d-tubocurarine (d-TC) induces irreversible inhibition of nicotinic acetylcholine receptor (nAChR) at the neuromuscular junction?", "sentence2": "An integrated model describing the interaction of nondepolarizing neuromuscular blocking agents with reversible anticholinesterase agents is derived and compared with a naive model using experimental data obtained from four anesthetized dogs. Three consecutive but separate steady-state d-tubocurarine blocks (approximately 50, 70, and 90%) were induced in each of the four dogs and reversed by short edrophonium infusions., The ability of hexamethonium (C6) to reverse the neuromuscular blocking action of tubocurarine (Tc), Volatile anesthetics enhance the neuromuscular blockade produced by nondepolarizing muscle relaxants (NDMRs). The neuromuscular junction is a postulated site of this interaction. We tested the hypothesis that volatile anesthetic enhancement of muscle relaxation is the result of combined drug effects on the nicotinic acetylcholine receptor., Concentration-effect curves for the inhibition of acetylcholine-induced currents were established for vecuronium, d-tubocurarine, isoflurane, and sevoflurane. Subsequently, inhibitory effects of NDMRs were studied in the presence of the volatile anesthetics at a concentration equivalent to half the concentration producing a 50% inhibition alone. All individually tested compounds produced rapid and readily reversible concentration-dependent inhibition., The pharmacological diversity of the different isoforms of the nicotinic acetylcholine receptor arises from the diversity of the subunits that assemble to form the native receptors. The aim of this study was to investigate the actions of the muscle relaxants d-tubocurarine, pancuronium and vecuronium on different isoforms of nicotinic acetylcholine receptors, At all three receptor types, d-tubocurarine and pancuronium blocked the responses elicited by acetylcholine in a reversible manner. , As further evidence of anticholinesterase activity, methamidophos (1-100 microM) was able to reverse the blockade by d-tubocurarine, There was an initial partial reversal of the neuromuscular inhibition caused by tubocurarine, Isoflurane and sevoflurane enhance the receptor blocking effects of nondepolarizing muscle relaxants on nicotinic acetylcholine receptors., Because other purinergic 2X (P2X) receptor antagonists, NF023 and NF279, do not have the reverse effects on the neuromuscular blockade of d-TC, the effect of NF449 seems irrelevant to inhibition of P2X receptors., The association rate constant for Tc binding to sites on the nicotinic acetylcholine receptor appears to be very fast (k+D = 8.9 x 10(8) M-1 s-1) and comparable to that for acetylcholine (ACh)., The aim of this study was to investigate the mechanism for the reversal effect of NF449 (a suramin analogue) on the neuromuscular block induced by d-tubocurarine (d-TC)., Study of the reversal effect of NF449 on neuromuscular blockade induced by d-tubocurarine.[SEP]Relations: Tubocurarine has relations: drug_drug with Acetylcholine, drug_drug with Acetylcholine, drug_drug with Succinylcholine, drug_drug with Succinylcholine, drug_drug with Naltrexone, drug_drug with Naltrexone, drug_drug with Acetyldigoxin, drug_drug with Acetyldigoxin. Acetylcholine has relations: drug_drug with Tubocurarine, drug_drug with Tubocurarine. Definitions: d-tubocurarine defined as following: A neuromuscular blocker and active ingredient in CURARE; plant based alkaloid of Menispermaceae.. Isoflurane defined as following: A stable, non-explosive inhalation anesthetic, relatively free from significant side effects.. isoforms defined as following: Refers to variants of the same protein which can be separated on special conducting media using electrophoresis. The differences may arise from genetically determined differences in primary structure or by modification of the same primary sequence.. Tc defined as following: Human CD55 wild-type allele is located in the vicinity of 1q32 and is approximately 40 kb in length. This allele, which encodes complement decay-accelerating factor protein, is involved in the modulation of complement activity.. acetylcholine defined as following: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.. hexamethonium defined as following: A nicotinic cholinergic antagonist often referred to as the prototypical ganglionic blocker. It is poorly absorbed from the gastrointestinal tract and does not cross the blood-brain barrier. It has been used for a variety of therapeutic purposes including hypertension but, like the other ganglionic blockers, it has been replaced by more specific drugs for most purposes, although it is widely used a research tool.. methamidophos defined as following: A synthetic organic thiophosphate compound and organophosphate acetylcholinesterase inhibitor and neurotoxin that is used as a pesticide. It is characterized as a volatile colorless or off-white crystalline solid with a pungent odor, and exposure occurs by inhalation, ingestion, or contact.. vecuronium defined as following: A synthetic, intermediate-acting mono-quaternary steroid and non-depolarizing neuromuscular blocking agent, with muscle relaxant activity. Vecuronium competitively binds to and blocks the nicotinic acetylcholine receptor at the neuromuscular junction, thereby preventing acetylcholine (ACh) binding and resulting in skeletal muscle relaxation and paralysis. Vecuronium has a shorter duration of action than pancuronium.. pancuronium defined as following: A bis-quaternary steroid that is a competitive nicotinic antagonist. As a neuromuscular blocking agent it is more potent than CURARE but has less effect on the circulatory system and on histamine release.. edrophonium defined as following: A rapid-onset, short-acting cholinesterase inhibitor used in cardiac arrhythmias and in the diagnosis of myasthenia gravis. It has also been used as an antidote to curare principles.. suramin defined as following: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.. muscle defined as following: Contractile tissue that produces movement in animals.. nicotinic acetylcholine receptors defined as following: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.. sevoflurane defined as following: A fluorinated isopropyl ether with general anesthetic property. Although the mechanism of action has not been fully elucidated, sevoflurane may act by interfering with the release and re-uptake of neurotransmitters at post-synaptic terminals, and/or alter ionic conductance following receptor activation by a neurotransmitter. Sevoflurane may also interact directly with lipid matrix of neuronal membranes, thereby affecting gating properties of ion channels. In addition, this agent may activate gamma-aminobutyric acid (GABA) receptors hyperpolarizing cell membranes. This results in a general anesthetic effect, a decrease in myocardial contractility and mean arterial pressure as well as an increased respiratory rate.. C6 defined as following: Complement component C6 (934 aa, ~105 kDa) is encoded by the human C6 gene. This protein is involved in complement-mediated host defense responses.. nicotinic acetylcholine receptor defined as following: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors..", "label": "no"} {"id": "converted_3340", "sentence1": "Is MLL3 part of the ASCOM complex?", "sentence2": "MLL3 as part of ASCOM complex, MLL3 as part of activating signal cointegrator-2 -containing complex (ASCOM)[SEP]Definitions: MLL3 defined as following: This gene plays a role in both methylation and transcriptional regulation.", "label": "yes"} {"id": "converted_4266", "sentence1": "Is cytokeratin a tumor marker?", "sentence2": "cytokeratin fragment antigen 21-1 (CYFRA21-1) in patients with laryngeal squamous cell carcinoma (LSCC) and its correlation with tumorigenesis and progression, cytokeratin fragment 19 (AUC=0.6882, p<0.0001) proved best in detecting relapse., The immunohistochemistry staining for cancer antigen 19-9, carcinoembryonic antigen, cytokeratin 20, and Ki-67 showed comparable intensities in both groups., evels of inflammatory and tumor markers, including carbohydrate antigen (CA) 19-9, CA125, carcinoembryonic antigen (CEA), CA153, and cytokeratin 19 fragments (CYFRA21-1), [SEP]Relations: Squamous cell carcinoma of the skin has relations: disease_phenotype_positive with porokeratosis (disease), disease_phenotype_positive with porokeratosis (disease), drug_effect with Sorafenib, drug_effect with Sorafenib, drug_effect with Maraviroc, drug_effect with Maraviroc, disease_phenotype_positive with xeroderma pigmentosum, disease_phenotype_positive with xeroderma pigmentosum. cellular response to carcinoembryonic antigen has relations: bioprocess_bioprocess with cellular response to glycoprotein, bioprocess_bioprocess with cellular response to glycoprotein. Definitions: CA125 defined as following: A carbohydrate antigen that occurs in tumors of the ovary as well as in breast, kidney, and gastrointestinal tract tumors and normal tissue. While it is tumor-associated, it is not tumor-specific and may have a protective function against particles and infectious agents at mucosal surfaces.. carcinoembryonic antigen defined as following: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment.. Ki-67 defined as following: This gene is involved in cellular proliferation.. cytokeratin 20 defined as following: A type I keratin expressed predominately in gastrointestinal epithelia, MERKEL CELLS, and the TASTE BUDS of the oral mucosa.. cytokeratin defined as following: This gene is involved in skin development..", "label": "yes"} {"id": "converted_3697", "sentence1": "Is SATB1 necessary for T-cell maturation?", "sentence2": "Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation., the transcription factor SATB1 that regulates the T-cell maturation, SATB1 is a transcriptional regulator controlling the gene expression that is essential in the maturation of the immune T-cell. , Special AT-rich sequence binding protein 1 (SATB1) regulates gene expression essential in immune T-cell maturation and switching of fetal globin species, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin remodeling. [SEP]Relations: Tat protein binding has relations: molfunc_protein with GABARAPL1, molfunc_protein with GABARAPL1, molfunc_protein with NPM1, molfunc_protein with NPM1, molfunc_protein with SMARCB1, molfunc_protein with SMARCB1, molfunc_protein with DLL1, molfunc_protein with DLL1, molfunc_protein with DNAJA1, molfunc_protein with DNAJA1. Definitions: T cells defined as following: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.. SATB1 defined as following: DNA-Binding Protein SATB1 (763 aa, ~86 kDa) is encoded by the human SATB1 gene. This protein binds DNA and may be involved in the regulation of transcription.. nuclear protein defined as following: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. matrix attachment regions defined as following: Regions of the CHROMATIN or DNA that bind to the NUCLEAR MATRIX. They are found in INTERGENIC DNA, especially flanking the 5' ends of genes or clusters of genes. Many of the regions that have been isolated contain a bipartite sequence motif called the MAR/SAR recognition signature sequence that binds to MATRIX ATTACHMENT REGION BINDING PROTEINS.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"} {"id": "converted_4450", "sentence1": "Is SOX10 expressed in melanoma cells?", "sentence2": "Our study confirmed that SOX10 is an oncogene and activate Notch signaling pathway, which suggests the potential treatment for melanoma patients by target SOX10/Notch axis., The most commonly used melanocytic markers include S100, Melan-A, HMB45 and SOX10, melanocytic markers melan-A and SOX10 [SEP]Relations: melanocytic neoplasm has relations: disease_disease with melanoma, disease_disease with melanoma, disease_disease with melanocytic skin neoplasm, disease_disease with melanocytic skin neoplasm, disease_disease with neoplasm (disease), disease_disease with neoplasm (disease), disease_disease with neurocristopathy, disease_disease with neurocristopathy. SUMOylation of transcription factors has relations: pathway_protein with CDKN2A, pathway_protein with CDKN2A. Definitions: Melan-A defined as following: A tumor-associated melanocytic differentiation antigen. Vaccination with MART-1 antigen may stimulate a host cytotoxic T-cell response against tumor cells expressing the melanocytic differentiation antigen, resulting in tumor cell lysis. (NCI04). melanoma defined as following: A benign or malignant, primary or metastatic neoplasm affecting the melanocytes.. HMB45 defined as following: A mouse monoclonal antibody that is used in anatomic pathology as a marker for melanocytic tumors. This antibody recognizes melanocyte protein PMEL (PMEL17 or SILV).. oncogene defined as following: Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of \"v-\" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix \"c-\" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.. S100 defined as following: Human S100A1 wild-type allele is located in the vicinity of 1q21 and is approximately 4 kb in length. This allele, which encodes protein S100-A1, is involved in the binding of zinc and calcium..", "label": "yes"} {"id": "converted_694", "sentence1": "Is there a phylogenetic analysis for HIV?", "sentence2": "The results of Burst and phylogenetic analysis suggested that the C. neoformans var. grubii strains could be separated into three nonredundant evolutionary groups (Burst group 1 to group 3). , Phylogenetic trees were constructed to evaluate the relationships between the variants, We analyzed pol (protease/reverse transcriptase) sequences from 135 newly diagnosed HIV-1-infected patients during the years 2009-2011. For phylogenetic relationships, sequences were aligned to the most recent reference data set from the Los Alamos database using BioEdit (version 7.1.3). The resulting alignment was analyzed with the Phylip package (version 3.67) building a neighbor-joining tree based on the Kimura two-parameter substitution model, . Phylogenetic analysis of gag gene were then performed using the MEGA 3.1 software, the gene distances were calculated by Distance program. There were three different HIV-1 subtypes including B, CRF01-AE and CRF07-BC present among twenty four MSMs in Zhengzhou, Phylogenetic analysis showed interpatient and intrapatient clustering of LTR nucleotide sequences., We evaluated the risk factors for intrafamilial transmission of HIV-1 infection through qualitative epidemiology following pol and env gene sequencing and phylogenetic analysis, Phylogenetic analysis has shown that the Siberian 10.RU.6637 isolate displays the highest sequence identity to the HIV-1 subtype AG forms circulating in Uzbekistan, Phylogenetic analysis showed that the evolutionary relationship of Env between HIV and SIV was the closest and they appeared to descend from a common ancestor, and the relationship of HIV and EIAV was the furthest, DI was confirmed when maximum sequence divergence was excessive and supported by phylogenetic analysis, (HIV-1) dual infection (DI) has been associated with decreased CD4 T-cell counts and increased viral loads; however, the frequency of intrasubtype DI is poorly understood., The aim of this study was to investigate the phylogenetic relationships of HIV-1 subtype C strains from Bangladesh and related strains from other countries, and thereby clarify when and from where subtype C was introduced in the country and how it subsequently spread within Bangladesh, This study characterized HCV genotype 5 sequences from South Africa, including six near full-length genomes, as well as the E1 region from an additional 12 genotype 5 samples. Phylogenetic analysis of these near full-length genome sequences revealed that all genotype 5 sequences formed a close cluster with high bootstrap support, The evolutionary history of the B subregion was not as clear as the C subregion, as the short length of this region yielded poor phylogenetic results, Finally, a phylogenetic tree was constructed to elucidate the observed pattern of HIV TDR[SEP]Relations: dentinogenesis imperfecta has relations: disease_phenotype_positive with Abnormality of the dental root, disease_phenotype_positive with Abnormality of the dental root, disease_phenotype_positive with Short dental roots, disease_phenotype_positive with Short dental roots, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance, disease_protein with DSPP, disease_protein with DSPP, disease_phenotype_positive with Persistence of primary teeth, disease_phenotype_positive with Persistence of primary teeth. Definitions: gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. sequences defined as following: The sequence of nucleotide residues along a DNA chain.. B defined as following:Deciduous maxillary right first molar tooth; Universal designation B; ISO designation 54
. EIAV defined as following: A species of LENTIVIRUS, subgenus equine lentiviruses (LENTIVIRUSES, EQUINE), causing acute and chronic infection in horses. It is transmitted mechanically by biting flies, mosquitoes, and midges, and iatrogenically through unsterilized equipment. Chronic infection often consists of acute episodes with remissions.. DI defined as following: An autosomal dominant disorder of tooth development characterized by opalescent dentin resulting in discoloration of the teeth. The dentin develops poorly with low mineral content while the pulp canal is obliterated.. gag gene defined as following: DNA sequences that form the coding region for proteins associated with the viral core in retroviruses. gag is short for group-specific antigen.. pol defined as following: An Indo-European West Slavic language spoken primarily in Poland as the native language of the Poles.. HIV defined as following: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS)..", "label": "yes"} {"id": "converted_2795", "sentence1": "Is chlorotoxin a peptide?", "sentence2": "chlorotoxin peptide , Chlorotoxin (CTX) is a 36-amino-acid disulfide-containing peptide derived from the venom of the scorpion Leiurus quinquestriatus., The mature Odontobuthus doriae chlorotoxin peptide has a 35-amino-acid residue and four disulfide bounds. , Chlorotoxin (CTX), a disulfide-rich peptide from the scorpion Leiurus quinquestriatus,[SEP]Relations: Cyclophosphamide has relations: drug_drug with Chloroquine, drug_drug with Chloroquine, drug_drug with Cephalexin, drug_drug with Cephalexin, drug_drug with Chlorthalidone, drug_drug with Chlorthalidone, drug_drug with Chlorzoxazone, drug_drug with Chlorzoxazone, drug_drug with Chlormadinone, drug_drug with Chlormadinone. Definitions: Chlorotoxin defined as following: A neurotoxin with potential anticancer property. Chlorotoxin (CTX) is a 36-amino acid peptide found in the venom of the deathstalker scorpion, and a chloride channel blocker. This toxin binds preferentially to glioma cells via the transmembrane endopeptidase matrix metalloproteinase-2 (MMP-2), and thereby prevents the spread of tumor cells. MMP-2 is specifically up-regulated in gliomas and related cancers, but is not normally expressed in brain.. venom defined as following: A toxin used by animals and injected into their victims by a bite or sting. CTX defined as following: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.. chlorotoxin a defined as following: A neurotoxin with potential anticancer property. Chlorotoxin (CTX) is a 36-amino acid peptide found in the venom of the deathstalker scorpion, and a chloride channel blocker. This toxin binds preferentially to glioma cells via the transmembrane endopeptidase matrix metalloproteinase-2 (MMP-2), and thereby prevents the spread of tumor cells. MMP-2 is specifically up-regulated in gliomas and related cancers, but is not normally expressed in brain.. peptide defined as following: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS..", "label": "yes"} {"id": "converted_88", "sentence1": "Is fatigue prevalent in patients receiving treatment for glioblastoma?", "sentence2": "By contrast, fatigue worsened over time, with a difference in mean score of 5.6 points between baseline and 4-month follow-up (P=.02)., In the GB cohort, the most common side effects were fatigue (56 %), diarrhea (44 %), neutropenia (31 %), and thrombocytopenia (25 %). , A total of 37 patients were treated, and treatment was well tolerated: grade 3, 4 nonhematologic toxicity occurred in 30% of patients and consisted mainly of fatigue (14%) and neuropathy (5%); grade 3, 4 hematologic toxicity occurred in 37% of patients and consisted of thrombocytopenia (30%), lymphopenia (4%), and neutropenia (4%). , Nonhematologic Grade 3 toxicity was rare, and included fatigue in 4 patients and cognitive disability in 1 patient., The most common grade 3 events were neutropenia, thrombocytopenia, fatigue, and infection in 25, 20, 13, and 10%, respectively. , Analysis of the results of the VAS Norris scale did not demonstrate an increase in emotional fatigue but did show an increase in physical fatigue that did not reach statistical significance. With regards to the MFI 20 tool, analysis of the results demonstrated a significant increase in general (P=0.0260) as well as physical (P=0.0141) fatigue but there was no difference in the other indices., This study demonstrated a progressive increase in physical fatigue in patients with glioblastoma relapse treated with irinotecan-bevacizumab. , One patient treated with temozolomide plus isotretinoin plus thalidomide had dose-limiting grade 3 fatigue and rash, and 1 patient receiving all 4 agents had dose-limiting grade 4 neutropenia. , The toxicities observed were primarily grade 1 and 2, and the most common were fatigue, hypertension, and headache. , Fatigue (41%), rash (62%), and loose stools (58%) constituted the most frequent adverse events, the majority of these being limited to Grade 1/2. , The most common grades 3 and 4 nonhematologic toxicities were nausea/vomiting (6.7%) and fatigue (5.8%). , Grade 3/4 toxicities included leukopenia (n = 1), lymphopenia (n = 2), thrombocytopenia (n = 1), ALT elevation (n = 3), AST elevation (n = 1), CNS hemorrhage (n = 1), fatigue (n = 1), and thrombotic/embolic events (n = 3); 8 patients required dose reduction. , The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%)., Bevacizumab-related toxicity included fatigue (16 patients; 4 grade 3), leukopenia (9; 1 grade 3), anemia (5; 0 grade 3), hypertension (7; 1 grade 3), deep vein thrombosis (4; 1 grade 3) and wound dehiscence (2; 1 grade 3). , Tiredness may be caused by the brain injury due to the tumor or the treatment in patients with glioblastoma multiforme (GBM). Some patients describe a sense of tiredness particularly after radiation or oral chemotherapy., Levels of tiredness in patients with GBM were greatly affected by the radiotherapy and oral chemotherapy (temozolomide)., The treatment had no negative effect on HRQOL, however, fatigue (P = 0.02) and constipation (P = 0.01) scales worsened over time., This regimen was well tolerated with grade 3/4 toxicities of fatigue, leukopenia, thrombocytopenia and rash requiring dose reductions. , The most common atrasentan-related toxicities were grade 1 or 2 rhinitis, fatigue, and edema., One patient developed Grade IV fatigue at the 100 ng/mL dose, but the MTD has not been established. , Side-effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. , Some patients suffered from fatigue and weak concentration about three months after the end of radiotherapy, in some cases even the neurologic state was deteriorated. , grade 1-2 common toxicities included fever, chills, fatigue, dizziness, nausea, vomiting and headache, neutrophilia and skin painful reactions appeared regularly at levels 3 and 4 (2.5 mg and 3.5 mg). , Ten episodes of grade 3/4 adverse events were observed in nine patients, including fatigue (n = 3), thrombocytopenia (n = 4), and myelotoxicity, febrile neutropenia, and pulmonary embolism (each n = 1)., Common adverse events were CTCAE grade 1-2 fatigue, loss of appetite, diarrhea, and nausea., The most common grade 3-4 toxicities were venous thrombosis, fatigue, skin reactions, encephalopathy, and neuropathy.[SEP]Relations: Fatigue has relations: disease_phenotype_positive with glioblastoma (disease), disease_phenotype_positive with glioblastoma (disease), disease_phenotype_positive with sporadic pheochromocytoma/secreting paraganglioma, disease_phenotype_positive with sporadic pheochromocytoma/secreting paraganglioma, phenotype_phenotype with Chronic fatigue, phenotype_phenotype with Chronic fatigue, disease_phenotype_positive with hereditary pheochromocytoma-paraganglioma, disease_phenotype_positive with hereditary pheochromocytoma-paraganglioma, drug_effect with Bortezomib, drug_effect with Bortezomib. Definitions: irinotecan-bevacizumab defined as following: A chemoimmunotherapy regimen consisting of irinotecan and bevacizumab that is used for the treatment of colon cancer.. hematologic defined as following: Pertaining to or related to the blood and blood-forming organs.. Fatigue defined as following: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.. lymphopenia defined as following: An abnormally small number of lymphocytes in the circulating blood.. glioblastoma multiforme defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO). isotretinoin defined as following: A topical dermatologic agent that is used in the treatment of ACNE VULGARIS and several other skin diseases. The drug has teratogenic and other adverse effects.. loss of appetite defined as following: A question about whether an individual has or had a loss of appetite.. temozolomide defined as following: A dacarbazine derivative that is used as an alkylating antineoplastic agent for the treatment of MALIGNANT GLIOMA and MALIGNANT MELANOMA.. conjunctivitis defined as following: INFLAMMATION of the CONJUNCTIVA.. loose stools defined as following: An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.. toxicities defined as following: The finding of bodily harm due to the poisonous effects of something.. brain injury defined as following: Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.. rash defined as following: Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (ERYTHEMA INFECTIOSUM), and sixth (EXANTHEMA SUBITUM) numeric designations survive as occasional synonyms in current terminology.. nausea/vomiting defined as following: Expelling the contents of the stomach and the sensations associated with it. They are symptoms of an underlying disease or condition and not a specific illness.. neuropathy defined as following: A disorder affecting the cranial nerves or the peripheral nervous system. It manifests with pain, tingling, numbness, and muscle weakness. It may be the result of physical injury, toxic substances, viral diseases, diabetes, renal failure, cancer, and drugs.. MTD defined as following: An autosomal dominant condition caused by mutation(s) in the TRPV4 gene, encoding transient receptor potential cation channel subfamily V member 4. It is characterized by a variable phenotype, which may include short limbs, kyphoscoliosis, and other skeletal abnormalities.. encephalopathy defined as following: A functional and/or structural disorder of the brain caused by diseases (e.g. liver disease, kidney disease), medications, chemicals, and injuries.. neutrophilia defined as following: Abnormally high level of neutrophils in the blood.. hemorrhage defined as following: Bleeding or escape of blood from a vessel.. chills defined as following: The sudden sensation of being cold. It may be accompanied by SHIVERING.. headache defined as following: The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.. thalidomide defined as following: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.. AST defined as following: Enzymes of the transferase class that catalyze the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 2.6.1.1.. leukopenia defined as following: A laboratory test result indicating a decreased number of white blood cells in the peripheral blood.. GBM defined as following: A sheet of amorphous extracellular material upon which the basal surfaces of epithelial cells rest and is the covering surface of a glomerular capillary, interposed between the cellular elements and the underlying connective tissue.. venous thrombosis defined as following: The formation or presence of a blood clot (THROMBUS) within a vein.. thrombocytopaenia defined as following: A subnormal level of BLOOD PLATELETS.. neutropenia defined as following: A decrease in the number of neutrophils in the peripheral blood.. blepharitis defined as following: Inflammation of the eyelids.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. ALT defined as following: Catalysis of the reaction: 2-oxoglutarate + L-alanine = L-glutamate + pyruvate. [EC:2.6.1.2, RHEA:19453]. constipation defined as following: Infrequent or difficult evacuation of FECES. These symptoms are associated with a variety of causes, including low DIETARY FIBER intake, emotional or nervous disturbances, systemic and structural disorders, drug-induced aggravation, and infections.. pulmonary embolism defined as following: Blocking of the PULMONARY ARTERY or one of its branches by an EMBOLUS.. infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. hypertension defined as following: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.. rhinitis defined as following: Inflammation of the NASAL MUCOSA, the mucous membrane lining the NASAL CAVITIES.. thrombocytopenia defined as following: An autosomal dominant disorder caused by mutation(s) in the ANKRD26 gene, encoding ANKRD26 protein. Additionally, in one family, a mutation(s) has been identified in the MASTL gene, encoding serine/threonine-protein kinase greatwall. The condition is characterized by mild to moderate bruisability.. fatigue defined as following: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.. glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO).", "label": "yes"} {"id": "converted_828", "sentence1": "Is muscle lim protein (MLP) involved in cardiomyopathies?", "sentence2": "Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease. In line with this notion, the homozygous loss of MLP results in cardiac hypertrophy and dilated cardiomyopathy. Moreover, MLP is induced in several models of cardiac hypertrophy such as aortic banding and myocardial infarction. , Muscle LIM protein (MLP) null mice are often used as a model for human dilated cardiomyopathy., A lack of MLP leads to an age-dependent impairment of excitation-contraction coupling with resulting contractile dysfunction and secondary fibrosis., Loss of murine MLP results in dilated cardiomyopathy, and mutations in human MLP lead to cardiac hypertrophy, indicating a critical role for MLP in maintaining normal cardiac function., Our data indicate that MLP contributes to muscle stiffness and is necessary for maximum work and power generation., Interestingly, MLP was also found to be down-regulated in humans with heart failure (Zolk et al. Circulation 101:2674-2677, 2000) and MLP mutations are able to cause hypertrophic and dilated forms of cardiomyopathy in humans (Bos et al. Mol Genet Metab 88:78-85, 2006; Geier et al. Circulation 107:1390-1395, 2003; Hershberger et al. Clin Transl Sci 1:21-26, 2008; Knöll et al. Cell 111:943-955, 2002; Knöll et al. Circ Res 106:695-704, 2010; Mohapatra et al. Mol Genet Metab 80:207-215, 2003)., MLP soon became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype (Arber et al. Cell 88:393-403, 1997). , Previous studies have shown an association between CSRP3 missense mutations and either dilated cardiomyopathy (DCM) or HCM, but all these studies were unable to provide comprehensive genetic evidence for a causative role of CSRP3 mutations. , We used a newly designed monoclonal antibody to show that muscle LIM protein (MLP), the protein encoded by CSRP3, is mainly a cytosolic component of cardiomyocytes and not tightly anchored to sarcomeric structures. Our functional data from both in vitro and in vivo analyses suggest that at least one of MLP's mutated forms seems to be destabilized in the heart of HCM patients harbouring a CSRP3 missense mutation., Muscle LIM protein (MLP) is a cytoskeletal protein located at the Z-disc of sarcomeres. Mutations in the human MLP gene are associated with hypertrophic and dilated cardiomyopathy., Our data demonstrate that Mlp84B is essential for normal cardiac function and establish the Drosophila model for the investigation of the mechanisms connecting defective cardiac Z-disc components to the development of cardiomyopathy., Muscle LIM protein (MLP) is a cytoskeletal LIM-only protein expressed in striated muscle. Mutations in human MLP are associated with cardiomyopathy;, TTN-encoded titin, CSRP3-encoded muscle LIM protein, and TCAP-encoded telethonin are Z-disc proteins essential for the structural organization of the cardiac sarcomere and the cardiomyocyte's stretch sensor. All three genes have been established as cardiomyopathy-associated genes for both dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). , Approximately 4.1% of unrelated patients had HCM-associated MLP or TCAP mutations. MLP/TCAP-HCM phenotypically mirrors myofilament-HCM and is more severe than the subset of patients who still remain without a disease-causing mutation. The precise role of W4R-MLP in the pathogenesis of either DCM or HCM warrants further investigation., MLP (muscle-LIM-protein) deficient mice develop DCM and changes in the mechanical coupling of cardiomyocytes result in alterations at the intercalated disks and enhanced accumulation of adherens junction proteins., Targeted deletion of cytoskeletal muscle LIM protein (MLP) in mice consistently leads to dilated cardiomyopathy (DCM) after one or more months. , In summary, young MLPKO mice revealed substantial alterations in passive myocardial properties and relaxation time, but not in most systolic characteristics. These results indicate that the progression to heart failure in the MLPKO model may be driven by diastolic myocardial dysfunction and abnormal passive properties rather than systolic dysfunction., Mice lacking the muscle LIM protein (MLP) develop morphological and clinical signs resembling human dilated cardiomyopathy and heart failure., Our results show that the absence of MLP causes a local loss of mitochondria. We hypothesize that this is caused by a disturbed interaction between cytoskeleton and mitochondria, which interferes with energy sensing and energy transfer. Recovery of energy depletion by stimulating mitochondrial biogenesis might be a useful therapeutic strategy for improving the energy imbalance in heart failure., Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM). In order to gain an insight into the molecular basis of the disease phenotype, we analysed the binding characteristics of wild-type MLP and of the (C58G) mutant MLP that causes hypertrophic cardiomyopathy., The molecular basis for HCM-causing mutations in the MLP gene might therefore be an alteration in the equilibrium of interactions of the ternary complex MLP-N-RAP-alpha-actinin., Muscle LIM protein (MLP) is a member of the cysteine-rich protein (CRP) family and has been implicated in both myogenesis and sarcomere assembly. In the latter role, it binds zyxin and alpha-actinin, both of which are involved in actin organization. An MLP-deficient mouse has been described; these mice develop dilated cardiomyopathy and heart failure., We identified a patient with DCM and EFE, having a mutation in MLP with the residue lysine 69 substituted by arginine (K69R). , MLP-knockout mice develop a marked cardiac hypertrophy reaction and dilated cardiomyopathy (DCM). MLP is therefore a candidate gene for heritable forms of hypertrophic cardiomyopathy (HCM) and DCM in humans., Family studies revealed cosegregation of clinically affected individuals with the respective mutations in MLP. CONCLUSION: Here, we present evidence that mutations in the CRP3/MLP gene can cause HCM., The skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. , Targeted disruption of muscle LIM protein (MLP) has previously been shown to result in dilated cardiomyopathy with many of the clinical signs of heart failure, although the effects of MLP disruption on passive ventricular mechanics and myocyte architecture are not known., These results suggest that the disruption of the cytoskeletal protein MLP results in less compliant passive tissue and concomitant structural alterations in the three-dimensional myocyte architecture that may in part explain the ventricular dysfunction in the dilated heart., Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, have been directly associated with human cardiomyopathies, whereas aberrant expression patterns are reported in human cardiac and skeletal muscle diseases., Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease., Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM)[SEP]Relations: muscle tissue has relations: anatomy_protein_present with MLXIP, anatomy_protein_present with MLXIP, anatomy_protein_present with LIMS1, anatomy_protein_present with LIMS1, anatomy_protein_present with MLIP, anatomy_protein_present with MLIP, anatomy_protein_present with LIMS3, anatomy_protein_present with LIMS3, anatomy_protein_present with MLPH, anatomy_protein_present with MLPH. Definitions: cysteine defined as following: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.. mitochondria defined as following: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed). cardiomyocytes defined as following: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).. heart muscle disease defined as following: A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).. muscle defined as following: Contractile tissue that produces movement in animals.. EFE defined as following: A condition characterized by the thickening of ENDOCARDIUM due to proliferation of fibrous and elastic tissue, usually in the left ventricle leading to impaired cardiac function (CARDIOMYOPATHY, RESTRICTIVE). It is most commonly seen in young children and rarely in adults. It is often associated with congenital heart anomalies (HEART DEFECTS CONGENITAL;) INFECTION; or gene mutation. Defects in the tafazzin protein, encoded by TAZ gene, result in a form of autosomal dominant familial endocardial fibroelastosis.. heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. zyxin defined as following: Zyxin (572 aa, ~61 kDa) is encoded by the human ZYX gene. This protein is involved in focal adhesion assembly and function.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. striated muscle defined as following: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.. cytosolic defined as following: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.. DCM defined as following: A chlorinated methotrexate derivative. Dichloromethotrexate inhibits the enzyme dihydrofolate reductase, thereby preventing the synthesis of purine nucleotides and thymidylates and inhibiting DNA and RNA synthesis. This agent is metabolized and excreted by the liver. (NCI04). HCM defined as following: A form of CARDIAC MUSCLE disease, characterized by left and/or right ventricular hypertrophy (HYPERTROPHY, LEFT VENTRICULAR; HYPERTROPHY, RIGHT VENTRICULAR), frequent asymmetrical involvement of the HEART SEPTUM, and normal or reduced left ventricular volume. Risk factors include HYPERTENSION; AORTIC STENOSIS; and gene MUTATION; (FAMILIAL HYPERTROPHIC CARDIOMYOPATHY).. dilated cardiomyopathy defined as following: Cardiomyopathy which is characterized by dilation and contractile dysfunction of the left and right ventricles. It may be idiopathic, or it may result from a myocardial infarction, myocardial infection, or alcohol abuse. It is a cause of congestive heart failure.. mutant defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. alpha-actinin defined as following: cytoskeletal protein present in Z lines of muscle fibrils and at sites of non-muscle cell contact with a substrate.. myocardial hypertrophy defined as following: Thickening of the myocardium often due to chronic pressure overload.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. myocyte defined as following: Mature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal (MUSCLE FIBERS, SKELETAL), cardiac (MYOCYTES, CARDIAC), and smooth (MYOCYTES, SMOOTH MUSCLE). They are derived from embryonic (precursor) muscle cells called MYOBLASTS.. Z-disc defined as following: Platelike region of a muscle sarcomere to which the plus ends of actin filaments are attached. [GOC:mtg_muscle, ISBN:0815316194]. arginine defined as following: An essential amino acid that is physiologically active in the L-form.. monoclonal antibody defined as following: A humanized monoclonal antibody directed against parathyroid hormone-related protein (PTH-rP). As a poly-hormone with diverse biological roles, PTH-rP is expressed by normal tissues, acting in local tissue environments in a variety of ways; it is commonly overexpressed by breast, prostate, and other cancers, acting systemically by promoting bone resorption, inhibiting calcium excretion from the kidney, inducing hypercalcemia, and possibly playing a role in the formation of bony metastases. By blocking the effects of PTH-rP on calcium metabolism, monoclonal antibody CAL may inhibit cancer-related hypercalcemia. (NCI04). genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. cytoskeletal defined as following: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.. sarcomere defined as following: The repeating contractile units of the MYOFIBRIL, delimited by Z bands along its length.. cytoskeletal protein defined as following: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. cardiac hypertrophy defined as following: Enlargement of the HEART due to chamber HYPERTROPHY, an increase in wall thickness without an increase in the number of cells (MYOCYTES, CARDIAC). It is the result of increase in myocyte size, mitochondrial and myofibrillar mass, as well as changes in extracellular matrix.. humans defined as following: Members of the species Homo sapiens.. ventricular dysfunction defined as following: A condition in which HEART VENTRICLES exhibit impaired function.. muscle stiffness defined as following: A feeling of tension or tightness in one or more muscles.. cardiomyopathies defined as following: A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS)..", "label": "yes"} {"id": "converted_3493", "sentence1": "Is there a BRCA mutation analysis in the Greek population?", "sentence2": "Comprehensive BRCA mutation analysis in the Greek population. Experience from a single clinical diagnostic center., Germline mutations in the BRCA1 and BRCA2 genes are associated with hereditary predisposition to breast and ovarian cancer. Sensitive and accurate detection of BRCA1 and BRCA2 mutations is crucial for personalized clinical management of individuals affected by breast or ovarian cancer, and for the identification of at-risk healthy relatives. We performed molecular analysis of the BRCA1 and BRCA2 genes in 898 Greek families, using Sanger sequencing or Next Generation Sequencing for the detection of small insertion/deletion frameshift, nonsynonymous, truncating and splice-site alterations and MLPA for the detection of large genomic rearrangements. In total, a pathogenic mutation was identified in 12.9% of 898 families analyzed. Of the 116 mutations identified in total 9% were novel and 14.7% were large genomic rearrangements. Our results indicate that different types of mutational events in the BRCA1 and BRCA2 genes are responsible for the hereditary component of breast/ovarian cancer in the Greek population. Therefore the methodology used in the analysis of Greek patients must be able to detect both point and small frameshift mutations in addition to large genomic rearrangements across the entire coding region of the two genes.[SEP]Relations: breast has relations: anatomy_protein_present with RIMKLB, anatomy_protein_present with RIMKLB, anatomy_protein_present with GCSAM, anatomy_protein_present with GCSAM. adaptation to pheromone regulating conjugation with mutual genetic exchange has relations: bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with regulation of conjugation, bioprocess_bioprocess with regulation of conjugation, bioprocess_bioprocess with negative adaptation of signaling pathway, bioprocess_bioprocess with negative adaptation of signaling pathway. Definitions: frameshift mutations defined as following: A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.. BRCA1 defined as following: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. It encodes a large nuclear protein that is a component of DNA repair pathways.. BRCA2 defined as following: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. Mutations in this gene predispose humans to breast and ovarian cancer. It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev 2000;14(11):1400-6). breast defined as following: In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.. ovarian cancer defined as following: A primary or metastatic malignant neoplasm involving the ovary. Most primary malignant ovarian neoplasms are either carcinomas (serous, mucinous, or endometrioid adenocarcinomas) or malignant germ cell tumors. Metastatic malignant neoplasms to the ovary include carcinomas, lymphomas, and melanomas.. coding region defined as following: A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"} {"id": "converted_1411", "sentence1": "Is the ACE inhibitor indicated for lung cancer treatment?", "sentence2": "The angiotensin converting enzyme (ACE) inhibitors are used widely as antihypertensive agents, and it has been suggested that they decrease the risk of some cancers, although available data are conflicting. , Using cell viability and fluorescent activated cell sorting analysis tests, we demonstrated that captopril inhibited the viability of LNM35 cells by inducing apoptosis, providing insight about the mechanisms underlying its antitumorigenic activities. In view of these experimental findings, we conclude that captopril could be a promising option for the treatment of lung cancer., In order to determine the mechanism by which captopril inhibited tumor growth, we investigated the impact of this drug on cell proliferation, apoptosis, and angiogenesis. Immunohistochemical analysis demonstrated that captopril treatment significantly reduced the number of proliferating cells (Ki-67) in the tumor samples but was not associated with inhibition of tumor angiogenesis (CD31)., Using this model, we demonstrated that daily IP administration of captopril (2.8 mg/mouse) for 3 weeks resulted in a remarkable reduction of tumor growth (58%, P < 0.01) and lymph node metastasis (50%, P= 0.088). , Angiotensin-converting enzyme (ACE) inhibitors have been shown to mitigate radiation-induced lung injury in preclinical models, ACE inhibitors may decrease the incidence of radiation pneumonitis in patients receiving thoracic radiation for lung cancer.[SEP]Relations: Captopril has relations: drug_protein with ACE, drug_protein with ACE, drug_drug with Acemetacin, drug_drug with Acemetacin, drug_drug with Acepromazine, drug_drug with Acepromazine, drug_drug with Acebutolol, drug_drug with Acebutolol, drug_drug with Aluminium acetoacetate, drug_drug with Aluminium acetoacetate. Definitions: drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. ACE inhibitors defined as following: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility.. CD31 defined as following: Human PECAM1 wild-type allele is located within 17q23 and is approximately 64 kb in length. This allele, which encodes platelet endothelial cell adhesion molecule protein, plays a role in transendothelial migration of leukocytes, angiogenesis, integrin activation, and may inhibit platelet-collagen interactions.. Angiotensin-converting enzyme defined as following: A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of ANGIOTENSIN I to ANGIOTENSIN II, with increase in vasoconstrictor activity, but no action on angiotensin II. It is also able to inactivate BRADYKININ, a potent vasodilator; and has a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. (From https://www.uniprot.org April 15, 2020).. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. captopril defined as following: A potent and specific inhibitor of PEPTIDYL-DIPEPTIDASE A. It blocks the conversion of ANGIOTENSIN I to ANGIOTENSIN II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the RENIN-ANGIOTENSIN SYSTEM and inhibits pressure responses to exogenous angiotensin.. Ki-67 defined as following: This gene is involved in cellular proliferation.. ACE inhibitor defined as following: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility..", "label": "no"} {"id": "converted_4655", "sentence1": "Is Erythropoietin effective for neuroprotection of Preterm Infants.", "sentence2": "BACKGROUND: High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established., There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P = 0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events.CONCLUSIONS: High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age., Based on existing evidence, it is still too early to recommend Epo as the standard treatment for preterm brain injury., Erythropoietin treatment of preterm infants did not result in neuroprotection at 2 years of age in two out of three published large randomized controlled trials; however, long-term follow-up of these infants is needed to come to definite conclusions.[SEP]Relations: Erythropoietin has relations: drug_effect with Pruritus, drug_effect with Pruritus, drug_effect with Pruritus, drug_effect with Pruritus, drug_drug with Prednimustine, drug_drug with Prednimustine, drug_drug with Prednimustine, drug_drug with Prednimustine, drug_drug with Transcrocetinate, drug_drug with Transcrocetinate. Definitions: death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. Erythropoietin defined as following: A recombinant glycosylated form of erythropoietin which stimulates the differentiation and proliferation of erythroid precursors. It is used for the treatment of ANEMIA associated with CHRONIC RENAL FAILURE in dialysis and predialysis patients.. erythropoietin defined as following: This gene is involved in the regulation of red blood cell production and function.. Epo defined as following: Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.. bronchopulmonary dysplasia defined as following: A chronic lung disease developed after OXYGEN INHALATION THERAPY or mechanical ventilation (VENTILATION, MECHANICAL) usually occurring in certain premature infants (INFANT, PREMATURE) or newborn infants with respiratory distress syndrome (RESPIRATORY DISTRESS SYNDROME, NEWBORN). Histologically, it is characterized by the unusual abnormalities of the bronchioles, such as METAPLASIA, decrease in alveolar number, and formation of CYSTS.. intracranial hemorrhage defined as following: Bleeding within the cranium.. retinopathy defined as following: Diseases involving the RETINA.. brain injury defined as following: Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.. prematurity defined as following: Birth when a fetus is less than 37 weeks and 0 days gestational age..", "label": "no"} {"id": "converted_1982", "sentence1": "Is lenvatinib effective for renal cell carcinoma?", "sentence2": "However, the combination of lenvatinib, a multitargeted agent that inhibits VEGF as well as FGF receptors, and everolimus demonstrated promising results in a randomized phase II trial. , The FDA has approved the combination of lenvatinib and everolimus to treat advanced or metastatic renal cell carcinoma., Moreover, a recent Phase II study demonstrated a significant benefit for the second-line combination treatment with everolimus plus lenvatinib (a novel TKI) in terms of progression-free survival and overall survival compared to the single-agent everolimus., We then discuss two recently approved growth factor receptor antagonists i.e. cabozantinib and lenvatinib, and a recently approved checkpoint inhibitor, nivolumab, and issues pertaining to drug development, and future directions in treatment of metastatic RCC. , INTERPRETATION: Lenvatinib plus everolimus and lenvatinib alone resulted in a progression-free survival benefit for patients with metastatic renal cell carcinoma who have progressed after one previous VEGF-targeted therapy. , Lenvatinib therapy for the treatment of patients with advanced renal cell carcinoma., Lenvatinib therapy for the treatment of patients with advanced renal cell carcinoma.[SEP]Relations: Lenvatinib has relations: drug_drug with Carbamazepine, drug_drug with Carbamazepine, drug_drug with Carbimazole, drug_drug with Carbimazole, drug_drug with Carfilzomib, drug_drug with Carfilzomib, drug_drug with Carbinoxamine, drug_drug with Carbinoxamine, drug_drug with Carbutamide, drug_drug with Carbutamide. Definitions: metastatic renal cell carcinoma defined as following: Renal cell carcinoma that has spread from the kidney to other anatomic sites.. VEGF defined as following: The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as \"tumor angiogenesis factor\" and \"vascular permeability factor\". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.. everolimus defined as following: A derivative of the natural macrocyclic lactone sirolimus with immunosuppressant and anti-angiogenic properties. In cells, everolimus binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate an immunosuppressive complex that binds to and inhibits the activation of the mammalian Target of Rapamycin (mTOR), a key regulatory kinase. Inhibition of mTOR activation results in the inhibition of T lymphocyte activation and proliferation associated with antigen and cytokine (IL-2, IL-4, and IL-15) stimulation and the inhibition of antibody production. (NCI05). FGF receptors defined as following: Specific molecular sites or structures on cell membranes that react with FIBROBLAST GROWTH FACTORS (both the basic and acidic forms), their analogs, or their antagonists to elicit or to inhibit the specific response of the cell to these factors. These receptors frequently possess tyrosine kinase activity.. nivolumab defined as following: A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Upon administration, nivolumab binds to and blocks the activation of PD-1, an immunoglobulin superfamily (IgSF) transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). This results in the activation of T-cells and cell-mediated immune responses against tumor cells. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity.. Lenvatinib defined as following: A synthetic, orally available inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR/FLK-1) tyrosine kinase with potential antineoplastic activity. Lenvatinib blocks VEGFR2 activation by VEGF, resulting in inhibition of the VEGF receptor signal transduction pathway, decreased vascular endothelial cell migration and proliferation, and vascular endothelial cell apoptosis.. cabozantinib defined as following: An orally bioavailable, small molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Cabozantinib strongly binds to and inhibits several RTKs, which are often overexpressed in a variety of cancer cell types, including hepatocyte growth factor receptor (MET), RET (rearranged during transfection), vascular endothelial growth factor receptor types 1 (VEGFR-1), 2 (VEGFR-2), and 3 (VEGFR-3), mast/stem cell growth factor (KIT), FMS-like tyrosine kinase 3 (FLT-3), TIE-2 (TEK tyrosine kinase, endothelial), tropomyosin-related kinase B (TRKB) and AXL. This may result in an inhibition of both tumor growth and angiogenesis, and eventually lead to tumor regression.. growth factor receptor defined as following: Cell surface receptors that bind growth or trophic factors with high affinity, triggering intracellular responses which influence the growth, differentiation, or survival of cells.. lenvatinib defined as following: A synthetic, orally available inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR/FLK-1) tyrosine kinase with potential antineoplastic activity. Lenvatinib blocks VEGFR2 activation by VEGF, resulting in inhibition of the VEGF receptor signal transduction pathway, decreased vascular endothelial cell migration and proliferation, and vascular endothelial cell apoptosis..", "label": "yes"} {"id": "converted_855", "sentence1": "Do carmustine wafers improve survival of glioblastoma patients?", "sentence2": "At recurrence, treatment options include repeat surgery (with or without Gliadel wafer placement), reirradiation or systemic therapy. , DISCUSSION: Carmustine wafers for primary HGG surgery in accordance with the NICE TA121 were associated with a median survival of 15.3 months; this is improved compared with previously reported randomised trials. Multimodal treatment with carmustine wafers, radical radiotherapy and concomitant temozolomide was associated with improved survival., Gliadel wafer is a new approach to the treatment of glioblastoma, which involves controlled release delivery of carmustine from biodegradable polymer wafers. It has shown promising results and provides a silver lining for glioblastoma patients., For patient with and without Gliadel, median and 1-year RFS were 12.9 months and 52% vs. 14 months and 42%, respectively (p = 0.89)., According to pathology, Gliadel did not influence OS of patients with Grade III or glioblastoma, CONCLUSION: In patients with high-grade gliomas, adding Gliadel before performing a Stupp protocol did not improve survival., Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. , CONCLUSIONS: The combination of aggressive resection, Gliadel wafer implantation, and GKS in addition to standard fractionated RT in selected patients resulted in increased local control and increased survival compared with a historical control group treated with surgery and involved-field RT alone., OBJECT: Gliadel (BCNU) wafer and concomitant temozolomide (TMZ) therapy, when used individually as adjuvant therapies, extend survival from that achieved by resection and radiation therapy (XRT) for glioblastoma multiforme (GBM). , BACKGROUND: Gliadel (polifeprosan 20 with carmustine [BCNU] implant) is commonly used for local delivery of BCNU to high-grade gliomas after resection and is associated with increased survival., Temozolomide administered according to this protocol produced a median survival benefit of 2 months in glioblastomas, and carmustine a similar benefit in high-grade gliomas., Analysis of a large trial by Westphal and colleagues (n = 240) showed a 29% risk reduction (P = 0.03) in the BCNU wafer-treated group over the course of the 30-month trial., Median survival of patients treated with BCNU wafers was 13.8 months vs 11.6 months in placebo-treated patients (P = 0.017) with a hazard ratio of 0.73 (P = 0.018), representing a 27% significant risk reduction. This survival advantage was maintained at 1, 2, and 3 years and was statistically significant (P = 0.01) at 3 years., CONCLUSION: Malignant glioma patients treated with BCNU wafers at the time of initial surgery in combination with radiation therapy demonstrated a survival advantage at 2 and 3 years follow-up compared with placebo., OBJECTIVE: Recently a randomized placebo-controlled phase III trial of biodegradable polymers containing carmustine has demonstrated a significant survival benefit for patients treated with local chemotherapy. , CONCLUSION: In this subgroup analysis of a phase III trial population both the clinical progression and radiological progression were significantly delayed in patients treated with local chemotherapy, resulting in an increased survival time., A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme. A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers., Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group (log-rank P -value stratified by country = 0.03), with a 29% reduction in the risk of death in the treatment group. When adjusted for factors affecting survival, the treatment effect remained positive with a risk reduction of 28% ( P = 0.03). , Controlled release delivery of carmustine from biodegradable polymer wafers was approved as an adjunct to surgical resection in the treatment of recurrent glioblastoma multiforme after it was shown in clinical trials to be well tolerated and effective. , Clinical trials have demonstrated significant improvements in survival and quality of life for patients after complete tumour resection and BCNU wafer implantation., BCNU wafers are an effective means of increasing survival and quality of life in patients diagnosed with malignant glioma, and are a valuable addition to the overall multimodal treatment strategy for these tumours., CONCLUSIONS: Carmustine wafer with concurrent TMZ and radiation followed by rotational chemotherapy is a well tolerated, effective therapy, and has a survival benefit compared with radiation alone., Median overall survival in 14 studies of newly-diagnosed patients suggested a modest improvement versus resection followed by Stupp protocol or resection with BCNU wafers, with an acceptable and manageable safety profile., The efficacy of carmustine wafers for older patients with glioblastoma multiforme: prolonging survival., DISCUSSION: Older patients with GBM may benefit from carmustine wafers. The survival for older patients who received carmustine wafers is significantly longer than matched patients who did not receive carmustine wafers., For glioblastoma patients who received ≥90% resection in the BCNU wafer study, median survival increased for BCNU wafer versus placebo (14.5 versus 12.4 months, respectively; P = 0.02), but no survival increase was found for <90% resection (11.7 versus 10.6 months, respectively; P = 0.98)., A wafer impregnated with carmustine, for use as an implant after surgical removal of recurrent GBM showed a prolongation in the median survival time of only 2 mo, from 20 to 28 wk in a study with a total of 222 patients. , No clear survival benefit associated with wafer implantation was identified., In three of the trials, patients with GBM who received carmustine wafers had significantly longer median survival than patients who did not receive wafers. , TMZ and carmustine (BCNU) biodegradable wafer (Gliadel) are the only adjuvant chemotherapies that have improved survival in randomised GB clinical trials . , The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events. , For patients undergoing repeat resection for malignant glioma, a randomized, blinded, placebo-controlled trial demonstrated a median survival for 110 patients who received carmustine polymers of 31 weeks compared with 23 weeks for 122 patients who only received placebo polymers., Median survival was improved from 11.6 to 13.9 months (P = 0.03), with a 29% reduction in the risk of death. When patients with glioblastoma multiforme alone were analyzed, the median survival improved from 11.4 to 13.5 months, but this improvement was not statistically significant. , OBJECT: Locoregional chemotherapy with carmustine wafers, positioned at surgery and followed by radiation therapy, has been shown to prolong survival in patients with newly diagnosed glioblastoma, as has concomitant radiochemotherapy with temozolomide., Following the resection of newly diagnosed or recurrent glioblastomas, local implantation of carmustine-impregnated biodegradable wafers (Gliadel) in the resection cavity constitutes an adjuvant therapy that can improve the possibilities of survival., The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events., However, patients with carmustine wafers demonstrated prolonged survival as compared to patients without wafers., The median survival for patients with carmustine wafers was 8.7 months, while median survival for patients without wafers was 5.5 months (P=0.007)., Likewise, in subgroup analysis, patients older than 70 years (P=0.0003) and 75 years (P=0.04) who had carmustine wafers had significantly longer survival than matched patients without wafers., Implantation of carmustine wafers did not significantly improve progression-free survival, In three of the trials, patients with GBM who received carmustine wafers had significantly longer median survival than patients who did not receive wafers, A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme, A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers, Following the resection of newly diagnosed or recurrent glioblastomas, local implantation of carmustine-impregnated biodegradable wafers (Gliadel) in the resection cavity constitutes an adjuvant therapy that can improve the possibilities of survival, Multimodal treatment with carmustine wafers, radical radiotherapy and concomitant temozolomide was associated with improved survival, The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events, TMZ and carmustine (BCNU) biodegradable wafer (Gliadel) are the only adjuvant chemotherapies that have improved survival in randomised GB clinical trials [SEP]Relations: Carmustine has relations: drug_effect with Renal insufficiency, drug_effect with Renal insufficiency, contraindication with lung disease, contraindication with lung disease, drug_effect with Diplopia, drug_effect with Diplopia, drug_effect with Erythema, drug_effect with Erythema, drug_effect with Stomatitis, drug_effect with Stomatitis. Definitions: glioblastoma multiforme defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO). malignant glioma defined as following: A grade 3 or grade 4 glioma arising from the central nervous system. This category includes glioblastoma, anaplastic astrocytoma, anaplastic ependymoma, anaplastic oligodendroglioma, and anaplastic oligoastrocytoma.. Carmustine defined as following: A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed). GBM defined as following: A sheet of amorphous extracellular material upon which the basal surfaces of epithelial cells rest and is the covering surface of a glomerular capillary, interposed between the cellular elements and the underlying connective tissue.. TMZ defined as following: A dacarbazine derivative that is used as an alkylating antineoplastic agent for the treatment of MALIGNANT GLIOMA and MALIGNANT MELANOMA.. glioblastomas defined as following: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.. gliomas defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21). wafers defined as following: A solid composed of a thin slice of material that contain active and/or inert ingredient(s).. tumours defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. polymers defined as following: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., BIOPOLYMERS; PLASTICS).. glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO). carmustine defined as following: A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed).", "label": "yes"} {"id": "converted_4686", "sentence1": "Is retinol binding protein 4 an adipokine?", "sentence2": "Systematic Quantification of Neurotrophic Adipokines RBP4, PEDF, and Clusterin in Human Cerebrospinal Fluid and Serum., Retinol-binding protein 4 (RBP4) is a prominent adipokine i, Fetuin-A and retinol-binding protein 4 (RBP4) are secreted as both hepatokine and adipokine. [SEP]Relations: retinol binding has relations: molfunc_protein with ADH4, molfunc_protein with ADH4, molfunc_protein with RBP4, molfunc_protein with RBP4, molfunc_protein with RBP5, molfunc_protein with RBP5, molfunc_protein with RBP3, molfunc_protein with RBP3, molfunc_protein with ADH7, molfunc_protein with ADH7. Definitions: adipokine defined as following: Polypeptides produced by the ADIPOCYTES. They include LEPTIN; ADIPONECTIN; RESISTIN; and many cytokines of the immune system, such as TUMOR NECROSIS FACTOR-ALPHA; INTERLEUKIN-6; and COMPLEMENT FACTOR D (also known as ADIPSIN). They have potent autocrine, paracrine, and endocrine functions.. retinol-binding protein 4 defined as following: Proteins which bind with RETINOL. The retinol-binding protein found in plasma has an alpha-1 mobility on electrophoresis and a molecular weight of about 21 kDa. The retinol-protein complex (MW=80-90 kDa) circulates in plasma in the form of a protein-protein complex with prealbumin. The retinol-binding protein found in tissue has a molecular weight of 14 kDa and carries retinol as a noncovalently bound ligand.. PEDF defined as following: Human SERPINF1 wild-type allele is located in the vicinity of 17p13.3 and is approximately 16 kb in length. This allele, which encodes pigment epithelium-derived factor protein, plays a role in both angiogenesis and cell proliferation. Mutation of the gene is associated with osteogenesis imperfecta type 12.. Clusterin defined as following: This gene may be involved in immunity, lipid metabolism and apoptosis.. Fetuin-A defined as following: A fetuin subtype that is synthesized by HEPATOCYTES and secreted into the circulation. It plays a major role in preventing CALCIUM precipitation in the BLOOD.. RBP4 defined as following: Retinol-binding protein 4 (201 aa, ~23 kDa) is encoded by the human RBP4 gene. This protein plays a role in retinol transport.. Human defined as following: Members of the species Homo sapiens..", "label": "yes"} {"id": "converted_2800", "sentence1": "Is P. gingivalis bacteria found in brain?", "sentence2": "studies using animal model of periodontitis and human post-mortem brain tissues from subjects with AD strongly suggest that a gram-negative periodontal pathogen, Porphyromonas gingivalis (Pg) and/or its product gingipain is/are translocated to the brain., The polymicrobial dysbiotic subgingival biofilm microbes associated with periodontal disease appear to contribute to developing pathologies in distal body sites, including the brain.[SEP]Relations: periodontal disease has relations: disease_disease with gingival disease, disease_disease with gingival disease, disease_protein with CTSC, disease_protein with CTSC. Periodontitis has relations: phenotype_phenotype with Abnormality of the gingiva, phenotype_phenotype with Abnormality of the gingiva, disease_phenotype_positive with dyskeratosis congenita, disease_phenotype_positive with dyskeratosis congenita, disease_phenotype_positive with cyclic hematopoiesis, disease_phenotype_positive with cyclic hematopoiesis. Definitions: periodontal disease defined as following: Pathological processes involving the PERIODONTIUM including the gum (GINGIVA), the alveolar bone (ALVEOLAR PROCESS), the DENTAL CEMENTUM, and the PERIODONTAL LIGAMENT.. Porphyromonas gingivalis defined as following: A species of gram-negative, anaerobic, rod-shaped bacteria originally classified within the BACTEROIDES genus. This bacterium produces a cell-bound, oxygen-sensitive collagenase and is isolated from the human mouth.. periodontitis defined as following: Inflammation and loss of connective tissues supporting or surrounding the teeth. This may involve any part of the PERIODONTIUM. Periodontitis is currently classified by disease progression (CHRONIC PERIODONTITIS; AGGRESSIVE PERIODONTITIS) instead of age of onset. (From 1999 International Workshop for a Classification of Periodontal Diseases and Conditions, American Academy of Periodontology). human defined as following: Members of the species Homo sapiens..", "label": "yes"} {"id": "converted_4161", "sentence1": "Does Curare function by stimulating the acetylcholine receptor?", "sentence2": "Usual clinical concentrations of curare cause competitive inhibition of muscle nicotinic acetylcholine receptors while higher concentrations may induce open channel blockade., nicotinic acetylcholine receptor (nAChR)-blocking agents [e.g., curare or alpha-bungarotoxin (alpha-BTX), The short neurotoxins to which erabutoxins belong act by blocking the nicotinic acetylcholine receptor, Both EFS- and carbachol-evoked contractions of the UES were blocked by curare at a lower concentration than by atropine or hexamethonium, suggesting that the acetylcholine receptor is nicotinic., We applied ACh alone; the nicotinic acetylcholine receptor (nAChR) antagonist curare, either alone or in the presence of ACh; and the muscarinic acetylcholine receptor (mAChR) antagonist atropine, either alone or in the presence of ACh., The EFS-induced contraction of the UES was completely blocked by tetrodotoxin and curare, and abolished in Ca2+ -free Ringer solution., Curare binding and the curare-induced subconductance state of the acetylcholine receptor channel., We have further investigated this particular mutation by examining the interaction of the competitive antagonist d-tubocurarine (curare) with the receptor., d-Tubocurarine (curare) is a well-characterized competitive antagonist of nicotinic acetylcholine receptors (AChRs), and it is usually assumed that curare and agonists share a common binding site., Curare action on nicotinic acetylcholine receptors has a number of facets, of which the best known is competitive antagonism., The mode of action of curare, a well-known competitive antagonist of acetylcholine at the nicotinic receptor, was examined with the single channel recording technique. , ently, however, it has been shown that curare can also block the channels opened by ACh at the frog neuromuscular junction as well as on rat and Aplysia neurones; moreover, curare is able to depolarize rat myotubes and thus behaves as an agonist for the cholinergic receptor of this preparation (see ref. 6). U, One site, competitively blocked by bungarotoxin and by curare, is presumably the acetylcholine receptor., In neuromuscular junction (NMJ) preparations, movements of the muscle must be inhibited if imaging during stimulation is desired (e.g., by application of curare, a potent acetylcholine receptor inhibitor)., Curare has long been regarded as a typical competitive antagonist of acetylcholine (ACh) at the vertebrate neuromuscular junction., Curare inhibition of wild-type receptors is consistent with curare binding to a single high-affinity binding site [inhibitor constant (Ki) = 20 nM]., Phenylalanine substitution for alpha Y198 [alpha Y198F (notation used here: subunit/amino acid in wild-type/residue number/substitution)] causes a 10-fold increase in curare affinity (Ki = 3.1 nM), and measurement of the recovery from curare inhibition indicates that this increase in affinity is due to a reduction in the rate of curare dissociation from the receptor., rthermore, sudden increases of research activity are ascribable to historic events, like the first use of curare as muscle relaxant during surgery.DIS, Recently, however, it has been shown that curare can also block the channels opened by ACh at the frog neuromuscular junction as well as on rat and Aplysia neurones; moreover, curare is able to depolarize rat myotubes and thus behaves as an agonist for the cholinergic receptor of this preparation (see ref., In Aplysia nervous tissue, curare appears not to be a specific antagonist for the nicotinic ACh receptor, but rather to be a specific blocking agent for a class of receptor-activated Na+ and Cl- responses., The mode of action of curare, a well-known competitive antagonist of acetylcholine at the nicotinic receptor, was examined with the single channel recording technique.[SEP]Relations: Muscarinic acetylcholine receptors has relations: pathway_protein with CHRM5, pathway_protein with CHRM5, pathway_protein with CHRM5, pathway_protein with CHRM5, pathway_protein with CHRM1, pathway_protein with CHRM1, pathway_protein with CHRM1, pathway_protein with CHRM1, pathway_protein with CHRM4, pathway_protein with CHRM4. Definitions: agonist defined as following: An agent that has affinity for a receptor and intrinsic activity at that receptor.. d-Tubocurarine defined as following: A neuromuscular blocker and active ingredient in CURARE; plant based alkaloid of Menispermaceae.. bungarotoxin defined as following: Neurotoxic proteins from the venom of the banded or Formosan krait (Bungarus multicinctus, an elapid snake). alpha-Bungarotoxin blocks nicotinic acetylcholine receptors and has been used to isolate and study them; beta- and gamma-bungarotoxins act presynaptically causing acetylcholine release and depletion. Both alpha and beta forms have been characterized, the alpha being similar to the large, long or Type II neurotoxins from other elapid venoms.. acetylcholine defined as following: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.. tetrodotoxin defined as following: An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction.. binding site defined as following: A Binding Site Domain is a region of protein that physically interacts stereospecifically, and usually at high affinity, with a specific ligand, substrate, or a specific domain of some complex target biomolecule, such as a protein, lipid, carbohydrate, or nucleic acid. Typically, but not necessarily, the interaction results in protein conformational alteration and functional modification.. cholinergic receptor defined as following: Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology.. muscle defined as following: Contractile tissue that produces movement in animals.. nicotinic acetylcholine receptor defined as following: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.. vertebrate defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. agonists defined as following: Used with chemicals, drugs, and endogenous substances to indicate substances or agents that have affinity for a receptor and intrinsic activity at that receptor. (From Textbook of Pharmacology, 1991, p.16). erabutoxins defined as following: Toxins isolated from the venom of Laticauda semifasciata, a sea snake (Hydrophid); immunogenic, basic polypeptides of 62 amino acids, folded by four disulfide bonds, block neuromuscular end-plates irreversibly, thus causing paralysis and severe muscle damage; they are similar to Elapid neurotoxins.. frog defined as following: genus of frog; tailess amphibian with long hind legs adapted for jumping; lives in damp or aquatic environments.. hexamethonium defined as following: A nicotinic cholinergic antagonist often referred to as the prototypical ganglionic blocker. It is poorly absorbed from the gastrointestinal tract and does not cross the blood-brain barrier. It has been used for a variety of therapeutic purposes including hypertension but, like the other ganglionic blockers, it has been replaced by more specific drugs for most purposes, although it is widely used a research tool.. UES defined as following: The structure at the pharyngoesophageal junction consisting chiefly of the cricopharyngeus muscle. It normally occludes the lumen of the ESOPHAGUS, except during SWALLOWING.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. muscarinic acetylcholine receptor defined as following: One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.. curare defined as following: Plant extracts from several species, including genera STRYCHNOS and Chondodendron, which contain TETRAHYDROISOQUINOLINES that produce PARALYSIS of skeletal muscle. These extracts are toxic and must be used with the administration of artificial respiration.. Phenylalanine defined as following: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.. acetylcholine receptor defined as following: Cell surface proteins that bind acetylcholine with high affinity and trigger intracellular changes influencing the behavior of cells. Cholinergic receptors are divided into two major classes, muscarinic and nicotinic, based originally on their affinity for nicotine and muscarine. Each group is further subdivided based on pharmacology, location, mode of action, and/or molecular biology..", "label": "no"} {"id": "converted_61", "sentence1": "Is c-met involved in the activation of the Akt pathway?", "sentence2": "Amplification of MET has been reported in approximately 5%-22% of lung tumors with acquired resistance to small-molecule inhibitors of the epidermal growth factor receptor (EGFR). Resistance to EGFR inhibitors is likely mediated through downstream activation of the phosphoinositide 3-kinase /AKT pathway., Simultaneous treatment of resistant tumors with a MET inhibitor plus an EGFR inhibitor can abrogate activation of downstream effectors of cell growth, proliferation, and survival, thereby overcoming acquired resistance to EGFR inhibitors., HGF mediated both ERK and Akt phosphorylation., ERK/Akt signaling, but not the Smad pathway, may be one of the main processes in HGF-induced EMT,, The MAPK/Akt pathway is indispensable in HGF/c-Met signaling., Inhibition of c-Met activation sensitizes osteosarcoma cells to cisplatin via suppression of the PI3K-Akt signaling, Specifically, we demonstrated that inhibition of c-Met activity led to suppression of the PI3K-Akt pathway, thus enhancing cisplatin chemosensitivity., Our study clearly suggests that inhibition of c-Met activity can effectively sensitize osteosarcoma cells to cisplatin via suppression of the PI3K-Akt signaling., We found that a dual Met/VEGF receptor 2 kinase inhibitor, E7050, circumvented HGF-induced EGFR-TKI resistance in EGFR mutant lung cancer cell lines by inhibiting the Met/Gab1/PI3K/Akt pathway in vitro., Here, we report that i) treatment of RL95-2 cells with HGF resulted in phosphorylation of the HGF receptor c-Met, activation of Akt and IκB, translocation of NF-κB into the nucleus, and up-regulation of COX-2 mRNA;, Our data suggest that HGF possesses chemotactic ability, has anti-apoptosis action, and induces cellular infiltration via the PI3K/Akt pathway;, Hepatocyte growth factor-induced c-Src-phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathway inhibits dendritic cell activation by blocking IκB kinase activity, Activation of c-Src in turn establishes a complex consisting of phosphatidylinositol 3-kinase and c-MET, and promotes downstream activation of the phosphatidylinositol 3-kinase/AKT pathway and mammalian target of rapamycin., Notably, hepatocyte growth factor-stimulated c-Src activation results in induction of phosphatidylinositol 3-kinase complexes p85α/p110α and p85α/p110δ, which is required for activation of mammalian target of rapamycin, and consequent inhibition of IκB kinase and nuclear factor-κB activation., Our findings, for the first time, have identified the c-Src-phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathway that plays a pivotal role in mediating the inhibitory effects of hepatocyte growth factor on dendritic cell activation by blocking nuclear factor-κB signaling., Cyr61 siRNA inhibited a second phase of Akt phosphorylation measured 12 hours after cell stimulation with HGF and also inhibited HGF-induced phosphorylation of the Akt target glycogen synthase kinase 3alpha., HGF+EGF treatment increased the duration of ERK1/2 and AKT activation compared to HGF or EGF alone. All these data indicate that a crosstalk between the EGF and HGF pathways in mammary epithelial cells may modulate the development of the mammary gland., Hepatocyte growth factor and c-Met promote dendritic maturation during hippocampal neuron differentiation via the Akt pathway, Consistent with these results, HGF activated Akt, which phosphorylates glycogen synthase kinase-3beta (GSK-3beta) to inactivate it, and reduced phosphorylation of microtubule-associated protein 2 (MAP2), which can promote microtubule polymerization and dendrite elongation when dephosphorylated., Conversely, pharmacological inhibition of c-Met with its specific inhibitor, PHA-665752, or genetic knock-down of c-Met with short hairpin RNAs (shRNAs) suppressed HGF-induced phosphorylation of Akt and GSK-3beta, increased phosphorylation of MAP2, and reduced dendrite number and length in cultured hippocampal neurons., Inhibiting Akt activity with the phosphoinositide-3-kinase inhibitor LY294002 or Akt inhibitor X suppressed HGF-induced phosphorylation of GSK-3beta, increased MAP2 phosphorylation, and blocked the ability of HGF to enhance dendritic length., These observations indicate that HGF and c-Met can regulate the early stages of dendrite maturation via activation of the Akt/GSK-3beta pathway., Involvement of PI3K/Akt signaling pathway in hepatocyte growth factor-induced migration of uveal melanoma cells, HGF was found to enhance cell migration, and that HGF-induced migration depends on PI3K/Akt pathway. The activation of PI3K/Akt pathway induced by the HGF/c-Met axis is involved in the downregulation of cell adhesion molecules E-cadherin and beta-catenin, contributing to the attenuation of cell-cell adhesion and promoting the enhanced motility and migration of uveal melanoma cells., HGF protects cultured cortical neurons against hypoxia/reoxygenation induced cell injury via ERK1/2 and PI-3K/Akt pathways, HGF stimulated both ERK1/2 and Akt activities in cortical neurons., Inhibition of ERK activation completely abolished the protective effects of HGF, and inhibition of Akt activation reduced, but did not completely eliminate the HGF mediated neuroprotection., It is suggested that the neuroprotection of HGF depend on ERK1/2 pathway, and, to a lesser extent, PI-3K/Akt pathway. , Met signals hepatocyte survival by preventing Fas-triggered FLIP degradation in a PI3k-Akt-dependent manner, Thus, Met acting on PI3K and Akt ensures high levels of FLIPL, and disruption of this pathway contributes to hepatic apoptosis and possibly to Fas-related liver diseases., The HGF-induced increase in Nkx 2.5 expression was inhibited by co-treatment with the PI3 kinase inhibitors Wortmannin and LY294002, but not by its inactive homolog LY303511, suggesting an involvement of the PI3 kinase/Akt pathway in this effect., X-Linked inhibitor of apoptosis protein expression level in colorectal cancer is regulated by hepatocyte growth factor/C-met pathway via Akt signaling, Activation of XIAP expression by HGF was inhibited by siRNA targeting Akt1 and Akt2., Activation of C-MET enhances XIAP through the Akt pathway., Hepatocyte growth factor prevents ventricular remodeling and dysfunction in mice via Akt pathway and angiogenesis, A significant reduction in apoptosis in the HGF-treated hearts was observed compared with control hearts, and was strongly associated with increased Akt activation., The antiapoptotic effect of HGF was mediated by activation of PI3-kinase/Akt pathway., The protective effect of HGF/SF against the ADR-induced apoptosis was abolished in the presence of either LY294002, an inhibitor of phosphatidylinositol-3'-OH kinase (PI3-K) or 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate, an inhibitor of Akt, thus implicating the activation of PI3-K-Akt signaling in the antiapoptotic action of HGF/SF., Immunoblotting analysis revealed that HGF/SF stimulated the sustained phosphorylation of Akt for several hours, Furthermore, ADR-induced activation of caspase-9, a downstream molecule of Akt, was inhibited for at least 24 h after HGF/SF stimulation,, These results indicate that HGF/SF, but not EGF, transmitted protective signals against ADR-induced apoptosis by causing sustained activation of the PI3-K-Akt signaling pathway., Hepatocyte growth factor/scatter factor inhibits UVB-induced apoptosis of human keratinocytes but not of keratinocyte-derived cell lines via the phosphatidylinositol 3-kinase/AKT pathway, When we analyzed the signaling pathways initiated by the HGF/SF receptor c-met, we found that the phosphatidylinositol (PI) 3-kinase and its downstream-element AKT and the mitogen-activated protein (MAP) kinase were activated., Inhibition of PI 3-kinase led to a complete abrogation of the anti-apoptotic effect of HGF/SF, whereas blockade of the MAP kinase pathway had no effect., We now show in detached cells a cooperative effect of HGF and FN in the activation of PI 3-kinase and on the phosphorylation of PKB/Akt at serine 473., PI 3-kinase activity is also required for the HGF- and fibronectin-induced survival responses, as well as anchorage-independent colony growth., Together, these results demonstrate that the PI 3-kinase/Akt pathway is a key effector of the HGF- and fibronectin-induced survival response of breast carcinoma cells under detached conditions and corroborate an interaction between integrin and HGF/ Met signalling pathways in the development of invasive breast cancer.[SEP]Relations: CTNNB1 has relations: protein_protein with AKT1, protein_protein with AKT1, protein_protein with AKT2, protein_protein with AKT2, pathway_protein with RHO GTPases activate IQGAPs, pathway_protein with RHO GTPases activate IQGAPs, pathway_protein with Deactivation of the beta-catenin transactivating complex, pathway_protein with Deactivation of the beta-catenin transactivating complex. phosphatidylinositol 3-kinase signaling has relations: bioprocess_protein with AKT1, bioprocess_protein with AKT1. Definitions: Akt1 defined as following: RAC-alpha serine/threonine-protein kinase (480 aa, ~56 kDa) is encoded by the human AKT1 gene. This protein is involved in signal transduction, serine/threonine phosphorylation, apoptosis regulation and neurogenesis.. Akt2 defined as following: RAC-beta serine/threonine-protein kinase (481 aa, ~56 kDa) is encoded by the human AKT2 gene. This protein is involved in protein phosphorylation, glucose metabolism, cell motility and signaling.. MAP2 defined as following: This gene plays a role in the removal of the amino-terminal methionine from nascent proteins.. phosphatidylinositol 3-kinase defined as following: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.. LY294002 defined as following: A morpholine-based inhibitor of phosphatidylinositol 3-kinase (PI3K) and the bromodomain and extra-terminal (BET) family of proteins, with potential antineoplastic activity. Upon administration, the PI3K/BET inhibitor LY294002 specifically targets and binds to both PI3K and the acetylated lysine recognition motifs in the bromodomains of BET proteins. Inhibition of PI3K activity inhibits the PI3K/AKT kinase signaling pathway. This may result in inhibition of growth and survival for tumor cells in which the PI3K-mediated signaling pathway is overactivated. Inhibition of BET proteins prevents their interaction with acetylated histones, disrupts chromatin remodeling and inhibits the expression of oncogenic drivers that are important for cell proliferation and survival, which together may lead to an inhibition of proliferation in BET-overexpressing tumor cells. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis. BET proteins, comprised of BRD2, BRD3, BRD4 and BRDT, are transcriptional regulators and play an important role during development and cellular growth. In tumor cells, BET proteins play a key role in the regulation of oncogene transcription and tumor cell proliferation.. integrin defined as following: A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors (RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.. C-MET defined as following: Human MET wild-type allele is located within 7q31 and is approximately 126 kb in length. This allele, which encodes hepatocyte growth factor receptor protein, plays a role in the regulation of cellular tyrosine-kinase activity. Mutations in the MET gene are associated with papillary renal carcinoma.. HGF defined as following: Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is PROTO-ONCOGENE PROTEINS C-MET.. Akt defined as following: Expressed in diverse tissues, Protein Kinase B (AKT/RAC Family) is a group (Alpha, Beta and Gamma) of cytoplasmic serine/threonine enzymes that covalently transfer the terminal, gamma phosphate group from ATP to a variety of substrate proteins and regulate cell signaling responses to insulin, PDGF, and IGF1 (through PI3K) involved in cell survival, cell proliferation, differentiation, apoptosis, glycogen synthesis, and glucose uptake.. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. caspase-9 defined as following: A long pro-domain caspase that contains a CASPASE RECRUITMENT DOMAIN in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.. cisplatin defined as following: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.. mammary gland defined as following: Glandular tissue in the BREAST of human that is under the influence of hormones such as ESTROGENS; PROGESTINS; and PROLACTIN. In WOMEN, after PARTURITION, the mammary glands secrete milk (MILK, HUMAN) for the nourishment of the young.. c-Src defined as following: Human SRC wild-type allele is located within 20q12-q13 and is approximately 61 kb in length. This allele, which encodes proto-oncogene tyrosine-protein kinase Src protein, plays a role in signal transduction pathways involved in the inhibition of endothelial cell apoptosis, regulation of the actin cytoskeleton, and the production of gonadotropins in pituitary cells. An allelic variant of the SRC gene, which produces a truncated, inactive protein, is associated with the development and metastasis of both breast and colon cancer.. microtubule defined as following: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.. GSK-3beta defined as following: A glycogen synthase kinase-3 type enzyme that functions in ENERGY METABOLISM; EMBRYONIC DEVELOPMENT; and NEUROGENESIS. It is also involved in PROTEIN BIOSYNTHESIS and regulates cell growth and proliferation as a component of the WNT SIGNALING PATHWAY and other signaling pathways. Certain polymorphisms in the GSK3B gene have been associated with PARKINSON DISEASE; ALZHEIMER DISEASE; and BIPOLAR DISORDER.. HGF/SF defined as following: Hepatocyte growth factor (728 aa, ~83 kDa) is encoded by the human HGF gene. This protein is involved in both the modulation of hepatocyte proliferation and growth factor receptor signaling in hepatocytes and many other cell types.. FN defined as following: Human FN1 wild-type allele is located in the vicinity of 2q34 and is approximately 76 kb in length. This allele, which encodes fibronectin protein, is involved in cellular adhesion, cellular motility, wound healing, neurite outgrowth, and cellular morphology.. phosphatidylinositol defined as following: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.. COX-2 defined as following: Human PTGS2 wild type allele is located within 1q25.2-q25.3 and is approximately 9 kb in length. This allele, which encodes prostaglandin G/H synthase 2 protein, plays a role in the stimulation of inflammatory responses.. dendrite defined as following: Extensions of the nerve cell body. They are short and branched and receive stimuli from other NEURONS.. dendritic cell defined as following: A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.. XIAP defined as following: This gene is involved in apoptotic regulation through caspase interaction.. ERK defined as following: A superfamily of PROTEIN SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).. rapamycin defined as following: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.. Wortmannin defined as following: An androstadiene metabolite produced by the fungi PENICILLIUM funiculosum that inhibits PHOSPHATIDYLINOSITOL-3-KINASES and alloantigen-specific activation of T-LYMPHOCYTES in human tumor cell lines. It is widely used in CELL BIOLOGY research and has broad therapeutic potential.. Cyr61 defined as following: Human CCN1 wild-type allele is located in the vicinity of 1p22.3 and is approximately 3 kb in length. This allele, which encodes CCN family member 1 protein, is involved in heart morphogenesis, angiogenesis, cell proliferation, cell adhesion and the positive regulation of apoptosis.. beta-catenin defined as following: This gene is involved in signal transduction and regulation of transcription.. lung tumors defined as following: Tumors or cancer of the LUNG.. PI3K defined as following: A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol into 1-phosphatidylinositol 3-phosphate.. EGF defined as following: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.. MET defined as following: A sulfur-containing essential L-amino acid that is important in many body functions.. nucleus defined as following: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). FLIP defined as following: Human CFLAR wild-type allele is located within 2q33-q34 and is approximately 48 kb in length. This allele, which encodes CASP8 and FADD-like apoptosis regulator protein, is involved in the modulation of caspase-mediated apoptosis and proteolysis.. IκB kinase defined as following: Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).. PI defined as following: Backflow of blood from the PULMONARY ARTERY into the RIGHT VENTRICLE due to imperfect closure of the PULMONARY VALVE..", "label": "yes"} {"id": "converted_1669", "sentence1": "Does ghrelin play a role in ischemic stroke?", "sentence2": "Recent evidence suggests that ghrelin may also be neuroprotective after injury in animal models of cerebral ischemia., Overall, these experiments point to a neurodegenerative but antiapoptotic effect of endogenous ghrelin in this model of global ischemia, highlighting that further research is essential before we can apply ghrelin treatments to neurodegenerative insults in the clinic., The serum ghrelin level was higher in the MCAO group when compared with the control group (P < 0.05). , Our results showed that higher level of serum ghrelin decreased gastrointestinal motility and damage to the intestinal mucosa existed in rats with MCAO., Leptin, adiponectin and ghrelin, new potential mediators of ischemic stroke., RESULTS: Significantly higher levels of leptin and lower levels of adiponectin and ghrelin were confirmed in the stroke group., Ghrelin levels correlated mildly with triglyceride levels, and were dominant in men with cardioembolic stroke., CONCLUSIONS: Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced., Ghrelin suppresses inflammation and neuronal nitric oxide synthase in focal cerebral ischemia via the vagus nerve., Compared with vehicle treatment, human ghrelin treatment in vagus nerve-intact rats after MCAO showed marked reduction in neurological deficit by 57% and infarct size by 25%. , Human ghrelin treatment in vagus nerve-intact rats significantly decreased the above measurements. Human ghrelin treatment also improved 7-day survival and significantly decreased neurological deficit over the entire 7 days after MCAO in vagus nerve-intact rats compared with vehicle. , Human ghrelin is thus a neuroprotective agent that inhibits inflammation, nNOS activity, and apoptosis in focal cerebral ischemia through a vagal pathway., Ghrelin is known to promote neuronal defense and survival against ischemic injury by inhibiting apoptotic processes. , Our data indicate that des-acyl ghrelin, as well as ghrelin, protect cortical neurons against ischemic injury through the inhibition of Par-4 expression and apoptotic molecules in mitochondrial pathway., In conclusion, it is considered that ghrelin as well as S-100B can be a useful marker for the prediction of stoke after CPB. , Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced., In this review we discuss pre-clinical evidence suggesting ghrelin may be a useful therapeutic in protecting the brain against injury after ischemic stroke., Both ghrelin and des-acyl ghrelin protected cortical neurons from ischemic injury., Our data indicate that des-acyl ghrelin, as well as ghrelin, protect cortical neurons against ischemic injury through the inhibition of Par-4 expression and apoptotic molecules in mitochondrial pathway., Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced., In this review we discuss pre-clinical evidence suggesting ghrelin may be a useful therapeutic in protecting the brain against injury after ischemic stroke, Human ghrelin is thus a neuroprotective agent that inhibits inflammation, nNOS activity, and apoptosis in focal cerebral ischemia through a vagal pathway, Both ghrelin and des-acyl ghrelin protected cortical neurons from ischemic injury, Overall, these experiments point to a neurodegenerative but antiapoptotic effect of endogenous ghrelin in this model of global ischemia, highlighting that further research is essential before we can apply ghrelin treatments to neurodegenerative insults in the clinic, In the present study, we investigated the role of prostate apoptosis response-4 (Par-4), a proapoptotic gene the expression of which is increased after ischemic injury, in ghrelin-mediated neuroprotection during middle cerebral artery occlusion (MCAO), Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced[SEP]Relations: Protein S human has relations: drug_drug with Cefazolin, drug_drug with Cefazolin, drug_drug with Cefazolin, drug_drug with Cefazolin, drug_drug with Nomegestrol, drug_drug with Nomegestrol, drug_drug with Nomegestrol, drug_drug with Nomegestrol, drug_drug with Zimelidine, drug_drug with Zimelidine. Definitions: Leptin defined as following: A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.. neuronal nitric oxide synthase defined as following: A CALCIUM-dependent, constitutively-expressed form of nitric oxide synthase found primarily in NERVE TISSUE.. nNOS defined as following: Human NOS1 wild-type allele is located within 12q24.2-q24.31 and is approximately 151 kb in length. This allele, which encodes nitric-oxide synthase, brain protein, is involved in nitric oxide biosynthesis from L-arginine and molecular oxygen. Certain allelic variants of the NOS1 gene are associated with susceptibility to either infantile hypertrophic pyloric stenosis or Parkinson's disease.. Par-4 defined as following: Proteinase-activated receptor 4 (385 aa, ~41 kDa) is encoded by the human F2RL3 gene. This protein plays a role in both the mediation of receptor signaling and the promotion of platelet activation.. cerebral ischemia defined as following: The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).. adiponectin defined as following: A 30-kDa COMPLEMENT C1Q-related protein, the most abundant gene product secreted by FAT CELLS of the white ADIPOSE TISSUE. Adiponectin modulates several physiological processes, such as metabolism of GLUCOSE and FATTY ACIDS, and immune responses. Decreased plasma adiponectin levels are associated with INSULIN RESISTANCE; TYPE 2 DIABETES MELLITUS; OBESITY; and ATHEROSCLEROSIS.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. gastrointestinal motility defined as following: The motor activity of the GASTROINTESTINAL TRACT.. rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810). prostate apoptosis response-4 defined as following: PRKC apoptosis WT1 regulator protein (340 aa, ~37 kDa) is encoded by the human PAWR gene. This protein plays a role in both the positive regulation of apoptosis and transcriptional repression.. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. Adipokines defined as following: Polypeptides produced by the ADIPOCYTES. They include LEPTIN; ADIPONECTIN; RESISTIN; and many cytokines of the immune system, such as TUMOR NECROSIS FACTOR-ALPHA; INTERLEUKIN-6; and COMPLEMENT FACTOR D (also known as ADIPSIN). They have potent autocrine, paracrine, and endocrine functions.. ischemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue..", "label": "yes"} {"id": "converted_321", "sentence1": "Is exonuclease Xrn1 a component of the P-bodies?", "sentence2": "PBs are associated with mRNA decay and contain the decapping enzymes DCP1/2, the 5' to 3' exonuclease Xrn1, the Lsm proteins (1-7), and the scaffolding proteins hedls/GE-1 and GW182. Both SGs and PBs contain mRNA, eIF4E, microRNAs and argonaute proteins, and various regulators of mRNA stability and translation (TTP, RCK/p54, and CPEB)., An alternative pathway of mRNA degradation occurs at processing bodies, cytoplasmic foci that contain decapping enzymes, the 5'-3' exonuclease Xrn1 and the Lsm1-7 heptamer. , n eukaryotic cells degradation of bulk mRNA in the 5' to 3' direction requires the consecutive action of the decapping complex (consisting of DCP1 and DCP2) and the 5' to 3' exonuclease XRN1. These enzymes are found in discrete cytoplasmic foci known as P-bodies or GW-bodies (because of the accumulation of the GW182 antigen)., Several proteins that stimulate mRNA decapping by the Dcp1:Dcp2 complex co-localize with Dcp1 and Dcp2, together with Xrn1, a 5'-to-3' exonuclease, to structures in the cytoplasm called processing bodies. , On the other hand, many P-body components including LSM1, GW182, DDX3, DDX6 and XRN1, but not others like DCP1a and EDC4 are recruited to the viral replication sites, as evidenced by their colocalization at perinuclear region with viral NS3., We identified the Pab 1801 cytoplasmic puncta as P Bodies (PBs), which are involved in mRNA regulation. We found that, in several cell lines, including U2OS, WI38, SK-N-SH and HCT116, the Pab 1801 puncta strictly colocalize with PBs identified with specific antibodies against the PB components Hedls, Dcp1a, Xrn1 or Rck/p54., The core components of P-bodies, including the decapping machinery (Dcp2 and Dhh1), 5'-3' exoribonuclease (Kem1/Xrn1), and the P-body scaffolding protein (Edc3), were identified and their localizations with respect to P-bodies were demonstrated., The second type of granules, piP-bodies, harbors the MIWI2-TDRD9-MAEL module of the piRNA pathway and signature components of P-bodies, GW182, DCP1a, DDX6/p54, and XRN1 proteins., In yeast and human tissue culture cells, Xrn1 has been shown to be a component of P-bodies (processing bodies), dynamic cytoplasmic granules where RNA degradation can take place., Here, we show that staufen- and FMRP-containing RNPs in Drosophila neurons contain proteins also present in somatic \"P bodies,\" including the RNA-degradative enzymes Dcp1p and Xrn1p/Pacman and crucial components of miRNA (argonaute), NMD (Upf1p), and general translational repression (Dhh1p/Me31B) pathways., In eukaryotic cells, XRN1 is often found in particles known as processing bodies (P bodies) together with other proteins involved in the 5' → 3' degradation pathway, such as DCP2 and the helicase DHH1 (Me31B). , In yeast and human tissue culture cells, Xrn1 has been shown to be a component of P-bodies (processing bodies), dynamic cytoplasmic granules where RNA degradation can take place, Owing to the essential functions of P bodies in mRNA regulation, we explored computationally the functional significance of SNPs in 7 P body components such as XRN1, DCP2, EDC3, CPEB1, GEMIN5, STAU1 and TRIM71, The core components of P-bodies, including the decapping machinery (Dcp2 and Dhh1), 5'-3' exoribonuclease (Kem1/Xrn1), and the P-body scaffolding protein (Edc3), were identified and their localizations with respect to P-bodies were demonstrated, Here, we show that staufen- and FMRP-containing RNPs in Drosophila neurons contain proteins also present in somatic "P bodies," including the RNA-degradative enzymes Dcp1p and Xrn1p/Pacman and crucial components of miRNA (argonaute), NMD (Upf1p), and general translational repression (Dhh1p/Me31B) pathways, P-body components LSM1, GW182, DDX3, DDX6 and XRN1 are recruited to WNV replication sites and positively regulate viral replication., The core components of P-bodies, including the decapping machinery (Dcp2 and Dhh1), 5'-3' exoribonuclease (Kem1/Xrn1), and the P-body scaffolding protein (Edc3), were identified and their localizations with respect to P-bodies were demonstrated. Various growth conditions, including glucose deprivation, hyperosmotic stress, and heat stress, stimulated the accumulation of P-bodies., Here we show that microscopically visible P-bodies are greatly diminished following West Nile viral infection, but the component proteins are not depleted. On the other hand, many P-body components including LSM1, GW182, DDX3, DDX6 and XRN1, but not others like DCP1a and EDC4 are recruited to the viral replication sites, as evidenced by their colocalization at perinuclear region with viral NS3., Owing to the essential functions of P bodies in mRNA regulation, we explored computationally the functional significance of SNPs in 7 P body components such as XRN1, DCP2, EDC3, CPEB1, GEMIN5, STAU1 and TRIM71. Computational analyses of non-synonymous SNPs of these components was initiated using well utilized publicly available software programs such as the SIFT, followed by PolyPhen, PANTHER, MutPred, I-Mutant-2., Xrn1 has been shown to be a component of P-bodies (processing bodies),, Here, we show that hDIS3L2 is an exosome-independent cytoplasmic mRNA 3'-5' exonuclease, which exhibits processive activity on structured RNA substrates in vitro. hDIS3L2 associates with hXRN1 in an RNA-dependent manner and can, like hXRN1, be found on polysomes, Inhibition of TAK1-JNK signaling also affected the number and size of P bodies and the localization of DCP1a, Xrn1, and Edc4., The organizing mechanism that forms P body foci in cells is unknown; however, potential scaffolding, aggregating, or other regulatory proteins found in P bodies were investigated for degradation. Two factors involved in 5'-end mRNA decapping and degradation, Xrn1 and Dcp1a, and the 3' deadenylase complex component Pan3 underwent accelerated degradation during infection, and Dcp1a may be a direct substrate of PV 3C proteinase., Secondly, P-bodies recruit mRNAs that are targeted for deadenylation and degradation by the decapping/Xrn1 pathway. , Depletion of TRN increased the number of P-bodies and stabilized ARE-containing mRNAs, as observed with knockdown of the 5'-3' exonuclease Xrn1., In this paper we show for the first time that Pacman, the Drosophila homologue of Xrn1, is localized in cytoplasmic particles in Drosophila testis cells. , Depletion of TRN increased the number of P-bodies and stabilized ARE-containing mRNAs, as observed with knockdown of the 5'-3' exonuclease Xrn1, These structures stain positively for a number of P-body and microRNP components, a microRNA-repressed mRNA and some translational repressors. They appear more heterogeneous than P-bodies of HeLa cells, and they rarely contain the exonuclease Xrn1 but are positive for rRNA.[SEP]Relations: 5'-3' exoribonuclease activity has relations: molfunc_protein with XRN1, molfunc_protein with XRN1, molfunc_protein with XRN2, molfunc_protein with XRN2, molfunc_protein with DCP2, molfunc_protein with DCP2. EDC3 has relations: bioprocess_protein with P-body assembly, bioprocess_protein with P-body assembly. CPEB1 has relations: cellcomp_protein with P-body, cellcomp_protein with P-body. Definitions: XRN1 defined as following: 5'-3' exoribonuclease 1 (1706 aa, ~194 kDa) is encoded by the human XRN1 gene. This protein plays a role in ribonucleotide metabolism.. yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. NMD defined as following: The nonsense-mediated decay pathway for nuclear-transcribed mRNAs degrades mRNAs in which an amino-acid codon has changed to a nonsense codon; this prevents the translation of such mRNAs into truncated, and potentially harmful, proteins. [GOC:krc, GOC:ma, PMID:10025395]. P-body defined as following: A focus in the cytoplasm where mRNAs may become inactivated by decapping or some other mechanism. Protein and RNA localized to these foci are involved in mRNA degradation, nonsense-mediated mRNA decay (NMD), translational repression, and RNA-mediated gene silencing. [GOC:clt, PMID:12730603]. HeLa cells defined as following: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays.. argonaute defined as following: Protein argonaute-1 (857 aa, ~97 kDa) is encoded by the human AGO1 gene. This protein is involved in RNA-mediated gene silencing.. DDX6 defined as following: This gene plays a role in the translation of mRNA encoded by genes involved in cell proliferation and malignant transformation.. PBs defined as following: A precise form of proton therapy that uses an electronically guided scanning system and magnets to deliver a proton beam that is millimeters wide. With this system, beam position and depth can be controlled, allowing for highly precise deposition of radiation to be delivered in all three dimensions of the tumor.. argonaute proteins defined as following: A protein family that is comprised of the catalytic components of the RNA-induced silencing complex.. rRNA defined as following: The most abundant form of RNA. Together with proteins, it forms the ribosomes, playing a structural role and also a role in ribosomal binding of mRNA and tRNAs. Individual chains are conventionally designated by their sedimentation coefficients. In eukaryotes, four large chains exist, synthesized in the nucleolus and constituting about 50% of the ribosome. (Dorland, 28th ed). TTP defined as following: Thrombotic thrombocytopenic purpura for which the cause is present from birth.. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.. Pan3 defined as following: Human NLRP6 wild-type allele is located in the vicinity of 11p15 and is approximately 7 kb in length. This allele, which encodes NACHT, LRR and PYD domains-containing protein 6, may play a role in the inflammatory response.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. eIF4E defined as following: A peptide initiation factor that binds specifically to the 5' MRNA CAP STRUCTURE of MRNA in the CYTOPLASM. It is a component of the trimeric complex EIF4F.. eukaryotic cells defined as following: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane.. cytoplasm defined as following: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990). granules defined as following: A solid composed of small particles or grains.. SGs defined as following: A rare, autosomal dominant inherited syndrome often caused by mutations in the SKI gene. It is characterized by premature fusion of skull bones and distinctive facial features, including a long, narrow head, hypertelorism, exophthalmos, downslanting palpebral fissures, a high, narrow palate, micrognathia, and low-set ears. The bodies of affected individuals resemble those of people with Marfan syndrome.. GW-bodies defined as following: A ribonucleoprotein granule located in the cytoplasm and the nucleus. GW-bodies minimally contain the Argonaute2 (Ago2) and TNRC6B proteins, together with specific target RNAs. [PMID:16418578, PMID:26930655, PMID:29576456]. DDX3 defined as following: Human DDX3X wild-type allele is located within Xp11.3-p11.23 and is approximately 31 kb in length. This allele, which encodes ATP-dependent RNA helicase DDX3X protein, plays a role in the modulation of RNA structure.. cell lines defined as following: Established cell cultures that have the potential to propagate indefinitely.. exoribonuclease defined as following: A family of enzymes that catalyze the exonucleolytic cleavage of RNA. It includes EC 3.1.13.-, EC 3.1.14.-, EC 3.1.15.-, and EC 3.1.16.-. EC 3.1.-. microRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. 5'-3' exoribonuclease defined as following: 5'-3' exoribonuclease 2 (950 aa, ~109 kDa) is encoded by the human XRN2 gene. This protein is involved in the mediation of RNA metabolism.. RNA defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). SNPs defined as following: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.. infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. regulatory proteins defined as following: Encoded by Regulatory Genes, Regulatory Proteins regulate or circumscribe the activity of many cellular functions.. human defined as following: Members of the species Homo sapiens.. polysomes defined as following: A ribosome bound to mRNA that forms part of a polysome. [GOC:jl]. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. hDIS3L2 defined as following: DIS3-like exonuclease 2 (885 aa, ~99 kDa) is encoded by the human DIS3L2 gene. This protein is involved in 3'-5'-exoribonuclease-mediated catabolism of polyuridylated RNA.. P-bodies defined as following: A focus in the cytoplasm where mRNAs may become inactivated by decapping or some other mechanism. Protein and RNA localized to these foci are involved in mRNA degradation, nonsense-mediated mRNA decay (NMD), translational repression, and RNA-mediated gene silencing. [GOC:clt, PMID:12730603]. exonuclease defined as following: This gene plays a role in DNA metabolic processes during stromal differentiation.. Xrn1 defined as following: 5'-3' exoribonuclease 1 (1706 aa, ~194 kDa) is encoded by the human XRN1 gene. This protein plays a role in ribonucleotide metabolism..", "label": "yes"} {"id": "converted_3054", "sentence1": "Is the yeast (Saccharomyces cerevisiae) genome organized into topologically associated domains (TADs)?", "sentence2": "Recent advances in our understanding of the three-dimensional organization of the eukaryotic nucleus have rendered the spatial distribution of genes increasingly relevant. In a recent work (Tsochatzidou et al., Nucleic Acids Res 45:5818-5828, 2017), we proposed the existence of a functional compartmentalization of the yeast genome according to which, genes occupying the chromosomal regions at the nuclear periphery have distinct structural, functional and evolutionary characteristics compared to their centromeric-proximal counterparts. Around the same time, it was also shown that the genome of Saccharomyces cerevisiae is organized in topologically associated domains (TADs), which are largely associated with the replication timing., Form and function of topologically associating genomic domains in budding yeast., Although similar structures appear to be conserved in fission yeast, computational modeling and analysis of high-throughput chromosome conformation capture (Hi-C) data have been used to argue that the small, highly constrained budding yeast chromosomes could not have these structures. In contrast, herein we analyze Hi-C data for budding yeast and identify 200-kb scale TADs, whose boundaries are enriched for transcriptional activity. Furthermore, these boundaries separate regions of similarly timed replication origins connecting the long-known effect of genomic context on replication timing to genome architecture. To investigate the molecular basis of TAD formation, we performed Hi-C experiments on cells depleted for the Forkhead transcription factors, Fkh1 and Fkh2, previously associated with replication timing. Forkhead factors do not regulate TAD formation, but do promote longer-range genomic interactions and control interactions between origins near the centromere. Thus, our work defines spatial organization within the budding yeast nucleus, demonstrates the conserved role of genome architecture in regulating DNA replication, and identifies a molecular mechanism specifically regulating interactions between pericentric origins., Around the same time, it was also shown that the genome of Saccharomyces cerevisiae is organized in topologically associated domains (TADs), which are largely associated with the replication timing., Around the same time, it was also shown that the genome of Saccharomyces cerevisiae is organized in topologically associated domains (TADs), which are largely associated with the replication timing. , In contrast, herein we analyze Hi-C data for budding yeast and identify 200-kb scale TADs, whose boundaries are enriched for transcriptional activity.[SEP]Relations: TFAP2 (AP-2) family regulates transcription of other transcription factors has relations: pathway_protein with CITED2, pathway_protein with CITED2, pathway_protein with TFAP2C, pathway_protein with TFAP2C, pathway_protein with TFAP2A, pathway_protein with TFAP2A, pathway_protein with PITX2, pathway_protein with PITX2. anatomical entity has relations: anatomy_anatomy with insect mouthpart, anatomy_anatomy with insect mouthpart. Definitions: Fkh1 defined as following: Human FOXO1 wild-type allele is located in the vicinity of 13q14.1 and is approximately 111 kb in length. This allele, which encodes forkhead box protein O1A, is involved in the modulation of transcription by RNA polymerase II.. TADs defined as following: Tietz syndrome is a genetic hypopigmentation and deafness syndrome characterized by congenital profound bilateral sensorineural hearing loss and generalized albino-like hypopigmentation of skin, eyes and hair.. genome defined as following: Anatomical set of genes in all the chromosomes.. Fkh2 defined as following: Human FOXG1 wild-type allele is located within 14q12-q13 and is approximately 4 kb in length. This allele, which encodes forkhead box protein G1, is involved in both the modulation of transcription by RNA polymerase II and in the regional development of the brain.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. Forkhead transcription factors defined as following: A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.. yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement..", "label": "yes"} {"id": "converted_2658", "sentence1": "Does International Citicoline Trial on acUte Stroke trial supports efficacy of citicoline for stroke treatment?", "sentence2": "The meta-analysis showed that no significant differences were found in the long-term mortality (OR=0.91, 95% CI 0.07 to 1.09, P=0.30), the rate of dependency (OR=1.02, 95% CI 0.87 to 1.24, P=0.85), and the effective rate (OR=0.98, 95% CI 0.84 to 1.14, P=0.82) between citicoline group and control group. , In conclusion, citicolne cannot reduce long-term mortality and dependence rate in the treatment of acute stroke, and the effective rate of citivoline may be not better than that of controls but with reliable safety., In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP-choline and placebo groups, CDP-choline was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with t-PA. , INTERPRETATION: Under the circumstances of the ICTUS trial, citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke., The trial was stopped for futility at the third interim analysis on the basis of complete data from 2078 patients., Global recovery was similar in both groups (odds ratio 1·03, 95% CI 0·86-1·25; p=0·364)., INTERPRETATION Under the circumstances of the ICTUS trial, citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke., In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP-choline and placebo groups, CDP-choline was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with t-PA. Several mechanisms have been proposed to explain the beneficial actions of CDP-choline., In humans, although a recent trial International Citicoline Trial on Acute Stroke (ICTUS) has shown that global recovery is similar in CDP-choline and placebo groups, CDP-choline was shown to be more beneficial in some patients, such as those with moderate stroke severity and not treated with t-PA.[SEP]Relations: Protein S human has relations: drug_drug with Coagulation Factor IX (Recombinant), drug_drug with Coagulation Factor IX (Recombinant), drug_drug with Ceftobiprole, drug_drug with Ceftobiprole, drug_drug with Ceftazidime, drug_drug with Ceftazidime, drug_drug with Cimicoxib, drug_drug with Cimicoxib, drug_drug with Potassium citrate, drug_drug with Potassium citrate. Definitions: CDP-choline defined as following: Donor of choline in biosynthesis of choline-containing phosphoglycerides.. t-PA defined as following: Tissue-type plasminogen activator (562 aa, ~63 kDa) is encoded by the human PLAT gene. This protein plays a role in the cleavage of plasminogen between Arg-580 and Val-581 to form the fibrinolytic enzyme plasmin.. stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810). humans defined as following: Members of the species Homo sapiens.. citicoline defined as following: Donor of choline in biosynthesis of choline-containing phosphoglycerides..", "label": "no"} {"id": "converted_3791", "sentence1": "Do nematodes contain a CTCF gene?", "sentence2": "Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes. We suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans., The most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode. , show that three ZF proteins from three basal nematodes cluster together with known CTCF proteins whereas no zinc finger protein of C. elegans and other derived nematodes does so.CO, SULTS: While orthologs for other insulator proteins were absent in all 35 analysed nematode species, we find orthologs of CTCF in a subset of nematodes. A, of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1. In contrast to earlier st, LUSION: Our findings show that CTCF and possibly chromatin insulation are present in basal nematodes. We , uggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. We , ESULTS: While orthologs for other insulator proteins were absent in all 35 analysed nematode species, we find orthologs of CTCF in a subset of nematodes. , suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. W, e show that three ZF proteins from three basal nematodes cluster together with known CTCF proteins whereas no zinc finger protein of C. elegans and other derived nematodes does so.CO, o investigate the pattern of CTCF occurrence in nematodes, we performed phylogenetic analysis with the ZF protein sets of completely sequenced nematodes. , r findings show that CTCF and possibly chromatin insulation are present in basal nematodes. W, propose a switch in the regulation of gene expression during nematode evolution, from the common vertebrate and insect type involving distantly acting regulatory elements and chromatin insulation to a so far poorly characterised mode present in more derived nematodes. H, We therefore searched in nematodes for orthologs of proteins that are involved in chromatin insulation.R, The unique secondary loss of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1.[SEP]Relations: Protein S human has relations: drug_drug with Loracarbef, drug_drug with Loracarbef, drug_drug with Nefazodone, drug_drug with Nefazodone, drug_drug with Cefditoren, drug_drug with Cefditoren, drug_drug with Cefdinir, drug_drug with Cefdinir, drug_drug with Cefsulodin, drug_drug with Cefsulodin. Definitions: nematode defined as following: class of unsegmented helminths with fundamental bilateral symmetry and secondary triradiate symmetry of the oral and esophageal structures; many species are parasites.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. CTCF defined as following: CCN family member 2 (349 aa, ~38kDa) is encoded by the human CCN2 gene. This protein plays a role in the promotion of proliferation and differentiation of chondrocytes and also mediates heparin- and divalent cation-dependent cell adhesion in many different cell types.. C. elegans defined as following: A species of nematode that is widely used in biological, biochemical, and genetic studies.. yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. CO defined as following: This gene plays a role in transmembrane transport of water.. vertebrate defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes.. CTCF gene defined as following: This gene is involved in epigenetic control of gene expression..", "label": "yes"} {"id": "converted_4017", "sentence1": "Is eptinezumab a small molecule?", "sentence2": "Eptinezumab-jjmr (referred to as eptinezumab hereafter; Vyepti™) is a humanised monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) and blocks its binding to the receptor. [SEP]Relations: Human calcitonin has relations: drug_effect with Eczema, drug_effect with Eczema, drug_drug with Zoledronic acid, drug_drug with Zoledronic acid, drug_effect with Epistaxis, drug_effect with Epistaxis, drug_effect with Eczematoid dermatitis, drug_effect with Eczematoid dermatitis, drug_effect with Tetany, drug_effect with Tetany. Definitions: CGRP defined as following: A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator.. calcitonin gene-related peptide defined as following: Calcitonin precursor (141 aa, ~15 kDa) is encoded by the human CALCA gene. This protein plays a role in calcium flux and bone resorption..", "label": "no"} {"id": "converted_3217", "sentence1": "Is ustekinumab a polyclonal antibody?", "sentence2": "Ustekinumab, a human monoclonal IgG1 antibody targeting the p40-subunit shared by interleukin (IL)12 and IL-23, represents a potential treatment for atopic dermatitis (AD).[SEP]Relations: Ustekinumab has relations: drug_drug with Ficlatuzumab, drug_drug with Ficlatuzumab, drug_protein with IL12B, drug_protein with IL12B, drug_drug with Ecromeximab, drug_drug with Ecromeximab, drug_drug with Daclizumab, drug_drug with Daclizumab, drug_drug with Teplizumab, drug_drug with Teplizumab. Definitions: atopic dermatitis defined as following: A chronic inflammatory genetically determined disease of the skin marked by increased ability to form reagin (IgE), with increased susceptibility to allergic rhinitis and asthma, and hereditary disposition to a lowered threshold for pruritus. It is manifested by lichenification, excoriation, and crusting, mainly on the flexural surfaces of the elbow and knee. In infants it is known as infantile eczema.. IL-23 defined as following: Binding to interleukin-23. [GOC:jl]. human defined as following: Members of the species Homo sapiens.. polyclonal antibody defined as following: A heterogeneous antibody derived from a host organism, typically produced by immunization of a suitable mammal with an antigen which induces B-lymphocytes to produce IgG immunoglobulins specific for the antigen. The resulting collection of antibodies have specificity for different epitopes of the antigen..", "label": "no"} {"id": "converted_2024", "sentence1": "Is the enzyme EPRS phosphorylated?", "sentence2": "Phosphorylation of glutamyl-prolyl tRNA synthetase (EPRS) has been investigated extensively in our laboratory for more than a decade, and has served as an archetype for studies of other AARSs., EPRS is dually phosphorylated by cyclin-dependent kinase 5 (Cdk5) at Ser(886) and then by a Cdk5-dependent-AGC kinase at Ser(999); , Diphosphorylated EPRS is released from its residence in the tRNA multisynthetase complex for immediate binding to NS1-associated protein and subsequent binding to ribosomal protein L13a and GAPDH. , Two-site phosphorylation of EPRS coordinates multimodal regulation of noncanonical translational control activity.[SEP]Relations: EPRS1 has relations: protein_protein with ESR2, protein_protein with ESR2, protein_protein with ESR1, protein_protein with ESR1, molfunc_protein with ATP binding, molfunc_protein with ATP binding, protein_protein with ARL4D, protein_protein with ARL4D, protein_protein with ASNS, protein_protein with ASNS. Definitions: GAPDH defined as following: Glyceraldehyde-3-phosphate dehydrogenase (335 aa, ~36 kDa) is encoded by the human GAPDH gene. This protein is involved in carbohydrate metabolism.. cyclin-dependent kinase 5 defined as following: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.. Cdk5 defined as following: Cyclin-dependent kinase 5 (292 aa, ~33 kDa) is encoded by the human CDK5 gene. This protein plays a role in protein phosphorylation and may be involved in cell cycle regulation..", "label": "yes"} {"id": "converted_835", "sentence1": "Is metabolic syndrome related with cardiovascular disease?", "sentence2": "The metabolic syndrome (MetS) is characterized by a cluster of risk factors including central obesity, hypertension, dyslipidemia and insulin resistance, The MetS is associated with an increased risk for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). , As a molecular link between metabolic signals, inflammation, and vascular dysfunction, resistin can be proposed as playing a significant role in the heightened inflammatory state induced by metabolic stress linked to excessive caloric intake, thus contributing to the risk for metabolic syndrome (MetS), type 2 diabetes (T2DM), and cardiovascular disease (CVD). , The metabolic syndrome (MetS) is associated with a higher risk for both, type 2 diabetes mellitus and cardiovascular disease. , arotid intima-media thickness (CIMT) has been widely used as a surrogate marker of atherosclerosis and cardiovascular disease (CVD)[SEP]Relations: metabolic syndrome X has relations: disease_disease with metabolic syndrome, disease_disease with metabolic syndrome, disease_disease with abdominal obesity-metabolic syndrome, disease_disease with abdominal obesity-metabolic syndrome, disease_disease with inborn errors of metabolism, disease_disease with inborn errors of metabolism. cardiovascular disease has relations: disease_disease with heart disease, disease_disease with heart disease, disease_disease with vascular disease, disease_disease with vascular disease. Definitions: resistin defined as following: Resistin (108 aa, ~11 kDa) is encoded by the human RETN gene. This protein plays a role in the regulation of insulin-mediated glucose metabolism.. MetS defined as following: Human ETV3 wild-type allele is located within 1q21-q23 and is approximately 17 kb in length. This allele, which encodes ETS translocation variant 3 protein, is involved in the repression of transcription by RNA polymerase II.. hypertension defined as following: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.. atherosclerosis defined as following: Thickening and loss of elasticity of the walls of ARTERIES of all sizes. There are many forms classified by the types of lesions and arteries involved, such as ATHEROSCLEROSIS with fatty lesions in the ARTERIAL INTIMA of medium and large muscular arteries.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. CVD defined as following: A spectrum of pathological conditions of impaired blood flow in the brain. They can involve vessels (ARTERIES or VEINS) in the CEREBRUM, the CEREBELLUM, and the BRAIN STEM. Major categories include INTRACRANIAL ARTERIOVENOUS MALFORMATIONS; BRAIN ISCHEMIA; CEREBRAL HEMORRHAGE; and others.. metabolic syndrome defined as following: A combination of medical conditions that when present, increase the risk of heart attack, stroke, and diabetes mellitus. It includes the following medical conditions: increased blood pressure, central obesity, dyslipidemia, impaired glucose tolerance, and insulin resistance.. dyslipidemia defined as following: A lipoprotein metabolism disorder characterized by decreased levels of high-density lipoproteins, or elevated levels of plasma cholesterol, low-density lipoproteins and/or triglycerides..", "label": "yes"} {"id": "converted_1644", "sentence1": "Is Calcium/Calmodulin dependent protein kinase II (CaMKII) involved in cardiac arrhythmias and heart failure?", "sentence2": "In human hypertrophy, both CaMKII and PKA functionally regulate RyR2 and may induce SR Ca(2+) leak. In the transition from hypertrophy to HF, the diastolic Ca(2+) leak increases and disturbed Ca(2+) cycling occurs. This is associated with an increase in CaMKII- but not PKA-dependent RyR2 phosphorylation. CaMKII inhibition may thus reflect a promising therapeutic target for the treatment of arrhythmias and contractile dysfunction., Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is an enzyme with important regulatory functions in the heart and brain, and its chronic activation can be pathological. CaMKII activation is seen in heart failure, and can directly induce pathological changes in ion channels, Ca(2+) handling and gene transcription., In the recent years, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) was suggested to be associated with cardiac hypertrophy and heart failure but also with arrhythmias both in animal models as well as in the human heart., Calcium-calmodulin-dependent protein kinase II (CaMKII) has emerged as a central mediator of cardiac stress responses which may serve several critical roles in the regulation of cardiac rhythm, cardiac contractility and growth. Sustained and excessive activation of CaMKII during cardiac disease has, however, been linked to arrhythmias, and maladaptive cardiac remodeling, eventually leading to heart failure (HF) and sudden cardiac death. , Overexpression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in transgenic mice results in heart failure and arrhythmias., From recent studies, it appears evident that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a central role in the arrhythmogenic processes in heart failure by sensing intracellular Ca(2+) and redox stress, affecting individual ion channels and thereby leading to electrical instability in the heart. , CaMKII activation is proarrhythmic in heart failure where myocardium is stretched., The Ca-calmodulin dependent kinase II (CaMKII) seems to be involved in the development of heart failure and arrhythmias and may therefore be a promising target for the development of antiarrhythmic therapies., Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is up-regulated in heart failure and has been shown to cause I(Na) gating changes that mimic those induced by a point mutation in humans that is associated with combined long QT and Brugada syndromes., CaMKII-dependent phosphorylation of Na(V)1.5 at multiple sites (including Thr-594 and Ser-516) appears to be required to evoke loss-of-function changes in gating that could contribute to acquired Brugada syndrome-like effects in heart failure., Because CaMKII expression and activity are increased in cardiac hypertrophy, heart failure, and during arrhythmias both in animal models as well as in the human heart a clinical significance of CaMKII is implied., The multifunctional Ca(2+)- and calmodulin-dependent protein kinase II (CaMKII) is now recognized to play a central role in pathological events in the cardiovascular system. CaMKII has diverse downstream targets that promote vascular disease, heart failure, and arrhythmias, so improved understanding of CaMKII signaling has the potential to lead to new therapies for cardiovascular disease., In our opinion, the multifunctional Ca and calmodulin-dependent protein kinase II (CaMKII) has emerged as a molecule to watch, in part because a solid body of accumulated data essentially satisfy Koch's postulates, showing that the CaMKII pathway is a core mechanism for promoting myocardial hypertrophy and heart failure. Multiple groups have now confirmed the following: (1) that CaMKII activity is increased in hypertrophied and failing myocardium from animal models and patients; (2) CaMKII overexpression causes myocardial hypertrophy and HF and (3) CaMKII inhibition (by drugs, inhibitory peptides and gene deletion) improves myocardial hypertrophy and HF, In contrast, inhibiting the CaMKII pathway appears to reduce arrhythmias and improve myocardial responses to pathological stimuli. , In this review, we discuss the important role of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in the regulation of RyR2-mediated Ca(2+) release. In particular, we examine how pathological activation of CaMKII can lead to an increased risk of sudden arrhythmic death. Finally, we discuss how reduction of CaMKII-mediated RyR2 hyperactivity might reduce the risk of arrhythmias and may serve as a rationale for future pharmacotherapeutic approaches., Transgenic (TG) Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) δ(C) mice develop systolic heart failure (HF). CaMKII regulates intracellular Ca(2+) handling proteins as well as sarcolemmal Na(+) channels. We hypothesized that CaMKII also contributes to diastolic dysfunction and arrhythmias via augmentation of the late Na(+) current (late I(Na)) in early HF (8-week-old TG mice)., Thus, late I(Na) inhibition appears to be a promising option for diastolic dysfunction and arrhythmias in HF where CaMKII is found to be increased., We tested the hypothesis that increased RyR2 phosphorylation by Ca(2+)/calmodulin-dependent protein kinase II is both necessary and sufficient to promote lethal ventricular arrhythmias., CONCLUSIONS: our results suggest that Ca(2+)/calmodulin-dependent protein kinase II phosphorylation of RyR2 Ca(2+) release channels at S2814 plays an important role in arrhythmogenesis and sudden cardiac death in mice with heart failure., Excessive activation of calmodulin kinase II (CaMKII) causes arrhythmias and heart failure, but the cellular mechanisms for CaMKII-targeted proteins causing disordered cell membrane excitability and myocardial dysfunction remain uncertain., Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias. We hypothesized that CaMKII contributes to arrhythmias and underlying cellular events and that inhibition of CaMKII reduces cardiac arrhythmogenesis in vitro and in vivo., We conclude that CaMKII contributes to cardiac arrhythmogenesis in TG CaMKIIdelta(C) mice having heart failure and suggest the increased SR Ca leak as an important mechanism. Moreover, CaMKII inhibition reduces cardiac arrhythmias in vitro and in vivo and may therefore indicate a potential role for future antiarrhythmic therapies warranting further studies., Ca2+/calmodulin dependent protein kinase II (CaMKII) can phosphorylate RyR2 and modulate its activity. This phosphorylation positively modulates cardiac inotropic function but in extreme situations such as heart failure, elevated CaMKII activity can adversely increase Ca2+ release from the SR and lead to arrhythmogenesis. , Calcium/calmodulin-dependent kinase II (CaMKII) is a multifunctional serine/threonine kinase expressed abundantly in the heart. CaMKII targets numerous proteins involved in excitation-contraction coupling and excitability, and its activation may simultaneously contribute to heart failure and cardiac arrhythmias., Under stress conditions, excessive CaMKII activity promotes heart failure and arrhythmias, in part through actions at Ca(2+) homeostatic proteins., Ca-calmodulin-dependent protein kinase II (CaMKII) was recently shown to alter Na(+) channel gating and recapitulate a human Na(+) channel genetic mutation that causes an unusual combined arrhythmogenic phenotype in patients: simultaneous long QT syndrome and Brugada syndrome. CaMKII is upregulated in heart failure where arrhythmias are common, and CaMKII inhibition can reduce arrhythmias. Thus, CaMKII-dependent channel modulation may contribute to acquired arrhythmic disease. , In heart failure (HF), Ca(2+)/calmodulin kinase II (CaMKII) expression is increased. Altered Na(+) channel gating is linked to and may promote ventricular tachyarrhythmias (VTs) in HF. Calmodulin regulates Na(+) channel gating, in part perhaps via CaMKII., Thus, CaMKII-dependent regulation of Na(+) channel function may contribute to arrhythmogenesis in HF., Recent findings that CaMKII expression in the heart changes during hypertrophy, heart failure, myocardial ischemia, and infarction suggest that CaMKII may be a viable therapeutic target for patients suffering from common forms of heart disease., Overexpression of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in transgenic mice results in heart failure and arrhythmias., Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias., BACKGROUND: Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias., CaMKII targets numerous proteins involved in excitation-contraction coupling and excitability, and its activation may simultaneously contribute to heart failure and cardiac arrhythmias., Calcium/calmodulin-dependent protein kinase II contributes to cardiac arrhythmogenesis in heart failure., From recent studies, it appears evident that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a central role in the arrhythmogenic processes in heart failure by sensing intracellular Ca(2+) and redox stress, affecting individual ion channels and thereby leading to electrical instability in the heart., Ryanodine receptor phosphorylation, calcium/calmodulin-dependent protein kinase II, and life-threatening ventricular arrhythmias., CaMKII targets numerous proteins involved in excitation-contraction coupling and excitability, and its activation may simultaneously contribute to heart failure and cardiac arrhythmias, The Ca-calmodulin dependent kinase II (CaMKII) seems to be involved in the development of heart failure and arrhythmias and may therefore be a promising target for the development of antiarrhythmic therapies, Calcium-calmodulin kinase II mediates digitalis-induced arrhythmias., Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)delta(C) mice have heart failure and isoproterenol (ISO)-inducible arrhythmias[SEP]Relations: calcium- and calmodulin-dependent protein kinase complex has relations: cellcomp_protein with CAMK2A, cellcomp_protein with CAMK2A, cellcomp_protein with CAMK2D, cellcomp_protein with CAMK2D, cellcomp_protein with CAMK2B, cellcomp_protein with CAMK2B, cellcomp_protein with CAMK2G, cellcomp_protein with CAMK2G, cellcomp_protein with CAMK1G, cellcomp_protein with CAMK1G. Definitions: protein kinase II defined as following: A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277). Calmodulin defined as following: Calmodulin (149 aa, ~17 kDa) is encoded by the human CALM1, CALM2 and CALM3 genes. This protein plays a role in the regulation of a number of enzymes, ion channels and signaling pathways.. diastolic dysfunction defined as following: Impairment in the filling of the ventricles during diastole. Causes include hypertrophic and restrictive cardiomyopathies, coronary artery disease, chronic high blood pressure, aortic stenosis, and aging.. Ryanodine receptor defined as following: A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.. ventricular arrhythmias defined as following: A disorder characterized by an electrocardiographic finding of an atypical cardiac rhythm resulting from a pathologic process in the cardiac ventricles.. heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. cardiac arrhythmias defined as following: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. hypertrophy defined as following: General increase in bulk of a part or organ due to CELL ENLARGEMENT and accumulation of FLUIDS AND SECRETIONS, not due to tumor formation, nor to an increase in the number of cells (HYPERPLASIA).. cardiac disease defined as following: Pathological conditions involving the HEART including its structural and functional abnormalities.. VTs defined as following: The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. HF defined as following: Abnormal accumulation of serous fluid in two or more fetal compartments, such as SKIN; PLEURA; PERICARDIUM; PLACENTA; PERITONEUM; AMNIOTIC FLUID. General fetal EDEMA may be of non-immunologic origin, or of immunologic origin as in the case of ERYTHROBLASTOSIS FETALIS.. isoproterenol defined as following: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.. cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. hyperactivity defined as following: Increased motor activity that is not goal directed.. myocardial ischemia defined as following: Thickening and loss of elasticity of the CORONARY ARTERIES, leading to progressive arterial insufficiency (CORONARY DISEASE).. CaMKII defined as following: This gene is involved in both protein phosphorylation and signaling.. sudden cardiac death defined as following: Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005). myocardial hypertrophy defined as following: Thickening of the myocardium often due to chronic pressure overload.. TG defined as following: Human TG wild-type allele is located in the vicinity of 8q24 and is approximately 268 kb in length. This allele, which encodes thyroglobulin protein, plays a role in the mediation of thyroid hormone production. Mutations in the gene are involved in goiter formation and genetic variants are associated with autoimmune thyroid disease type 3.. PKA defined as following: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.. vascular disease defined as following: Pathological processes involving any of the BLOOD VESSELS in the cardiac or peripheral circulation. They include diseases of ARTERIES; VEINS; and rest of the vasculature system in the body.. point mutation defined as following: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.. genetic mutation defined as following: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.. SR defined as following: Human SNCG wild-type allele is located within10q23.2-q23.3 and is approximately 13 kb in length. This allele, which encodes gamma-synuclein protein, plays a role in the modulation of axonal architecture and neurofilament integrity. This gene is highly expessed in advanced breast carcinomas, suggesting a correlation between SNCG overexpression and breast tumor development.. cell membrane defined as following: Any of the lipid bilayer membranes within a cell.. Brugada syndrome defined as following: An autosomal dominant defect of cardiac conduction that is characterized by an abnormal ST-segment in leads V1-V3 on the ELECTROCARDIOGRAM resembling a right BUNDLE-BRANCH BLOCK; high risk of VENTRICULAR TACHYCARDIA; or VENTRICULAR FIBRILLATION; SYNCOPAL EPISODE; and possible sudden death. This syndrome is linked to mutations of gene encoding the cardiac SODIUM CHANNEL alpha subunit.. transgenic mice defined as following: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.. gene deletion defined as following: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.. Transgenic defined as following: Experimental organism whose genome has been altered by the transfer of a gene or genes from another species or breed.. cardiac hypertrophy defined as following: Enlargement of the HEART due to chamber HYPERTROPHY, an increase in wall thickness without an increase in the number of cells (MYOCYTES, CARDIAC). It is the result of increase in myocyte size, mitochondrial and myofibrillar mass, as well as changes in extracellular matrix.. humans defined as following: Members of the species Homo sapiens.. infarction defined as following: Formation of an infarct, which is NECROSIS in tissue due to local ISCHEMIA resulting from obstruction of BLOOD CIRCULATION, most commonly by a THROMBUS or EMBOLUS.. myocardium defined as following: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.. systolic heart failure defined as following: Heart failure caused by abnormal myocardial contraction during SYSTOLE leading to defective cardiac emptying..", "label": "yes"} {"id": "converted_2605", "sentence1": "Does verubecestat activate BACE?", "sentence2": "Verubecestat is a potent BACE1 enzyme inhibitor currently being investigated in Phase III trials for the treatment of mild-to-moderate and prodromal Alzheimer's disease. [SEP]Relations: Protein S human has relations: drug_drug with Caplacizumab, drug_drug with Caplacizumab, drug_drug with Mofebutazone, drug_drug with Mofebutazone, drug_drug with Bortezomib, drug_drug with Bortezomib, drug_drug with Cefodizime, drug_drug with Cefodizime, drug_drug with Cefbuperazone, drug_drug with Cefbuperazone. Definitions: Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. BACE1 defined as following: Beta-secretase 1 (501 aa, ~56 kDa) is encoded by the human BACE1 gene. This protein plays a role in the proteolysis of ectodomains of membrane proteins..", "label": "no"} {"id": "converted_4610", "sentence1": "Do RNA binding Proteins that bind to adenine uridine (AU)-rich elements (AREs) in the 5' untranslated region (UTR) of mRNAs (AU-RBPs) regulate the DNA Damage Response?", "sentence2": " We investigated 2 mRNA-binding proteins - HuR and TIAR showing specificity to AU-Rich Element (ARE) sites in 3'UTR of mRNA., Bioinformatics analysis of the human SOD1 mRNA 3' untranslated region (3'UTR) demonstrated the presence of HuD binding adenine-uridine (AU)-rich instability-conferring elements (AREs)., We found that AU-rich element RNA binding protein 1 (AUF1) directly binds to the Cry1 3'UTR and regulates translation of Cry1 mRNA., Adenylate/uridylate-rich elements (AREs) are the most common cis-regulatory elements in the 3'-untranslated region (UTR) of mRNAs, where they fine-tune turnover by mediating mRNA decay., HuR binding to AU-rich elements present in the 3' untranslated region of Classical swine fever virus., Previous reports indicate that distinct RNA sequence in the BDNF 3'UTRs differentially regulates BDNF production in the brain to accommodate neuronal activity changes, conceivably through differential interactions with undefined trans-acting factors that regulate stability and translation of these BDNF mRNA isoforms., The 5' untranslated region (UTR) of CSFV contains the IRES, which is a highly structured element that recruits the translation machinery., Although AU-rich elements (AREs) in the 3'UTR of interleukin-6 (IL-6) mRNA dictate mRNA degradation, the role of TTP in the post-transcriptional regulation of IL-6 gene expression is unclear., We cloned the full-length cDNA of rabbit RGS4, which contains a long 3'-untranslated region (UTR) with several AU-rich elements (AREs)., Luciferase reporter assays demonstrate that HuR specifically regulates FOXO1 expression through AU-rich elements (AREs) within the FOXO1 3' UTR., Additionally, we demonstrated that RNPC1 could bind to PR mRNA via AU-rich elements (AREs) within PR 3'-untranslated region (3'-UTR) and then enhance PR mRNA stability., Here, we find that CXCR4 harbors AU-rich elements (AREs) in the 3'-untranslated region (3'-UTR) that bind and respond to the RNA-binding proteins, tristetraprolin (TTP/ZFP36) and HuR (ELAVL1)., These proteins bind to adenine uridine-rich element (ARE) in the 3'untranslated region of target messenger RNA and stimulate target degradation., t mRNAs. RNA-binding proteins can control mRNA stability by binding to AU- and U-rich elements located in the 3'-untranslated regions (3'-UTRs) of target, y RNA-binding proteins (RBPs) have been shown to recognize and bind to mRNAs that contains AREs generally present in the 3'UTR of mRNAs. RBPs , at AREs in the 3'UTR control TSP-1 mRNA stability and that the RNA binding protein AUF1 participates in this control. These studies suggest t, mber of the Elav family of RNA-binding proteins, has been implicated in this pathway through its binding to adenine and uridine (AU)-rich stability elements (ARE) located in the 3' untranslated regions (3'-UTRs) of the mRNA. Whereas three , Hu proteins are RNA-binding proteins that are implicated in the control of stabilization, nuclear export, and/or translation of specific mRNAs with AU-rich elements (AREs) in the 3'-untranslated region. Th, Post-transcriptional mRNA regulation by RNA binding proteins (RBPs) associated with AU-rich elements (AREs) present in the 3' untranslated region (3'UTR) of specific mRNAs modulates transcript stability and translation in eukaryotic cells., In the 3'-untranslated region, the destabilizing adenine-uridine (AU)-rich elements (AREs) control the expression of several transcripts through interactions with ARE-binding proteins (AUBPs) and RNA degradation machinery., The AU/U-rich element-binding protein HuR has been shown to bind to p53 mRNA 3'UTR and enhance translation in response to DNA-damaging UVC radiation., The AUF1 (hnRNPD) and HuR (ELAV-like) proteins, potential trans-acting factors for regulated mRNA decay, bind in vitro to A+U-rich elements (AREs) found in the 3' untranslated region (3' UTR) of many labile transcripts., NCL binds to the AU-rich element (ARE) in the 3'UTR of target mRNAs, mediates miRNA functions in the nearby target sequences, and regulates mRNA deadenylation., We investigated 2 mRNA-binding proteins - HuR and TIAR showing specificity to AU-Rich Element (ARE) sites in 3'UTR of mRNA., Secondly, the degradation of some mRNAs related to immune responses has been reported to be regulated by binding of RNA-binding proteins to adenylate uridylate-rich elements (AU-rich elements, AREs) located in the 3'-untranslated region (3'-UTR)., Here, we review the interplay between six well-known RBPs (TTP, AUF-1, KSRP, HuR, TIA-1, and TIAR) that recognize AU-rich elements (AREs) at the 3' untranslated regions of mRNAs, namely ARE-RBPs., Hu proteins have been shown to bind to AU-rich elements (AREs) in the 3'-untranslated region of unstable mRNAs.[SEP]Relations: ELAVL1 has relations: molfunc_protein with mRNA 3'-UTR AU-rich region binding, molfunc_protein with mRNA 3'-UTR AU-rich region binding, molfunc_protein with mRNA 3'-UTR binding, molfunc_protein with mRNA 3'-UTR binding. protein binding has relations: molfunc_protein with UTP6, molfunc_protein with UTP6, molfunc_protein with AUP1, molfunc_protein with AUP1, molfunc_protein with AUNIP, molfunc_protein with AUNIP. Definitions: IL-6 defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine interleukin-6 (IL-6) with antiapoptotic, proinflammatory, antiinflammatory, proproliferative and proangiogenic activities. IL-6 binds to its receptor (IL-6R), activating a receptor-CD130 receptor complex; the CD130 portion of the complex is a signal transduction protein that activates JAK kinases and Ras-mediated signaling pathways, which in turn activate downstream signaling pathways, resulting in the activation of various transcription factors (STAT, ELK-1, NF-IL-6, etc.) and gene transcription. The physiological effects of IL-6 are complex and varied and include hematopoietic, pyrogenic and thermogenic, proinflammatory, antiinflammatory, proproliferative (anti-apoptotic), and angiogenic effects.. BDNF defined as following: A member of the nerve growth factor family of trophic factors. In the brain BDNF has a trophic action on retinal, cholinergic, and dopaminergic neurons, and in the peripheral nervous system it acts on both motor and sensory neurons. (From Kendrew, The Encyclopedia of Molecular Biology, 1994). TIA-1 defined as following: Human TIA1 wild-type allele is located in the vicinity of 2p13 and is approximately 39 kb in length. This allele, which encodes nucleolysin TIA-1 isoform p40, plays a role in both RNA binding and splicing. Mutation of the gene is associated with Welander distal myopathy.. TTP defined as following: Thrombotic thrombocytopenic purpura for which the cause is present from birth.. adenine defined as following: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.. ARE defined as following: A unit of area equal to 100 square meters. Are is a non-SI unit accepted for use with SI.. tristetraprolin defined as following: A ZINC FINGER MOTIF containing transcription factor that was originally identified as one of the IMMEDIATE-EARLY PROTEINS. It shuttles between the CYTOPLASM and the CELL NUCLEUS and is involved in destabilization of mRNAs for TUMOR NECROSIS FACTOR-ALPHA.. RNA sequence defined as following: The sequence of nucleotide residues along an RNA chain.. NCL defined as following: A group of severe neurodegenerative diseases characterized by intracellular accumulation of autofluorescent wax-like lipid materials (CEROID; LIPOFUSCIN) in neurons. There are several subtypes based on mutations of the various genes, time of disease onset, and severity of the neurological defects such as progressive DEMENTIA; SEIZURES; and visual failure.. FOXO1 defined as following: This gene is involved in transcriptional regulation and may play a role in myogenic growth and differentiation.. Cry1 defined as following: This gene plays a role in circadian rhythm.. HuR defined as following: This gene plays a role in the regulation of gene expression.. hnRNPD defined as following: Heterogeneous nuclear ribonucleoprotein D0 (355 aa, ~38 kDa) is encoded by the human HNRNPD gene. This protein is involved in both RNA transport and splicing.. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.. transcript defined as following: The initial RNA molecule produced by transcription.. CXCR4 defined as following: Combining with the C-X-C motif chemokine 12 (CXCL12) and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. [GOC:bf, PMID:22204316]. IRES defined as following: Sequences within MESSENGER RNA that enable PROTEIN TRANSLATION INITIATION independent of 5' CAPPED RNA.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. eukaryotic cells defined as following: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane.. 3' UTR defined as following: The sequence at the 3' end of messenger RNA that does not code for product. This region contains transcription and translation regulating sequences.. RNA binding proteins defined as following: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.. RNPC1 defined as following: Human RBM38 wild-type allele is located in the vicinity of 20q13.31 and is approximately 18 kb in length. This allele, which encodes RNA-binding protein 38, plays a role in the regulation of mRNA stability.. AUF1 defined as following: Human HNRNPD wild-type allele is located in the vicinity of 4q21 and is approximately 22 kb in length. This allele, which encodes heterogeneous nuclear ribonucleoprotein D0, plays a role in the catabolism of RNA.. Th defined as following: Tyrosine 3-monooxygenase (528 aa, ~59 kDa) is encoded by the human TH gene. This protein plays a role in the synthesis of dopamine from L-tyrosine.. trans-acting factors defined as following: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.. p53 defined as following: Human TP53 wild-type allele is located in the vicinity of 17p13.1 and is approximately 19 kb in length. This allele, which encodes cellular tumor antigen p53 protein, plays a role in cell cycle regulation during the G0/G1transition. Alterations of the TP53 gene occur as both somatic and germline mutations in human malignancies in select cancer-prone families with Li-Fraumeni syndrome.. TSP-1 defined as following: An extracellular matrix glycoprotein from platelets and a variety of normal and transformed cells of both mesenchymal and epithelial origin. Thrombospondin-1 is believed to play a role in cell migration and proliferation, during embryogenesis and wound repair. Also, it has been studied for its use as a potential regulator of tumor growth and metastasis..", "label": "no"} {"id": "converted_3280", "sentence1": "Is Protoporphyrinogen oxidase localized to the mitochondrium?", "sentence2": "We showed that 28 amino acids in the amino terminus of PPOX contain an independently functioning signal for mitochondrial targeting., Based on our results we propose a mechanism for protoporphyrinogen oxidase targeting to the mitochondrion., Mitochondrial targeting of human protoporphyrinogen oxidase., In the present study, PfPPO has been cloned, expressed and shown to be localized to the mitochondrion by immunofluorescence microscopy. [SEP]Relations: Mitochondrial inheritance has relations: disease_phenotype_positive with mitochondrial myopathy with reversible cytochrome C oxidase deficiency, disease_phenotype_positive with mitochondrial myopathy with reversible cytochrome C oxidase deficiency, disease_phenotype_positive with cytochrome-c oxidase deficiency disease, disease_phenotype_positive with cytochrome-c oxidase deficiency disease, disease_phenotype_positive with striatonigral degeneration, disease_phenotype_positive with striatonigral degeneration, disease_phenotype_positive with ophthalmoplegic neuromuscular disorder with abnormal mitochondria, disease_phenotype_positive with ophthalmoplegic neuromuscular disorder with abnormal mitochondria, disease_phenotype_positive with Kearns-Sayre syndrome, disease_phenotype_positive with Kearns-Sayre syndrome. Definitions: Mitochondrial defined as following: The distribution of mitochondria, including the mitochondrial genome, into daughter cells after mitosis or meiosis, mediated by interactions between mitochondria and the cytoskeleton. [GOC:mcc, PMID:10873824, PMID:11389764]. protoporphyrinogen oxidase defined as following: A membrane-bound flavoenzyme that catalyzes the oxygen-dependent aromatization of protoporphyrinogen IX (Protogen) to protoporphyrin IX (Proto IX). It is the last enzyme of the common branch of the HEME and CHLOROPHYLL pathways in plants, and is the molecular target of diphenyl ether-type herbicides. VARIEGATE PORPHYRIA is an autosomal dominant disorder associated with deficiency of protoporphyrinogen oxidase.. PPOX defined as following: Human HCRT wild-type allele is located in the vicinity of 17q21 and is approximately 1 kb in length. This allele, which encodes orexin protein, plays a role in both G-protein coupled receptor signaling and feeding behavior. Mutation of the gene is associated with narcolepsy 1..", "label": "yes"} {"id": "converted_680", "sentence1": "Is signal transducer and activator of transcription-3 (STAT3) critical for tumor angiogenesis progression?", "sentence2": " (STAT3) is critical for cancer progression by regulating tumor cell survival, proliferation, and angiogenesis. Herein, we investigated the regulation of STAT3 activation and the therapeutic effects of Icaritin, a prenyl flavonoid derivative from Epimedium Genus, in renal cell carcinoma (RCC). , Overall, these results suggest that Icaritin strongly inhibits STAT3 activation and is a potentially effective therapeutic option for the treatment of renal cell carcinoma, we have reviewed important signaling pathways that are closely related to radiosensitization, such as cell cycle arrest, tumor angiogenesis, JAK/STAT3 signaling pathway and Mismatch repair, Interleukin-27 signaling is mediated by the JAK-STAT pathway via activation of STAT1 and STAT3, which have tumor suppressive and oncogenic activities, respectively. Epithelial-mesenchymal transition (EMT) and angiogenesis are key processes in carcinogenesis., The inhibition of STAT3 activation had no effect on the development of the epithelial phenotype., STAT3 plays a vital role in inducing and maintaining a pro-carcinogenic inflammatory microenvironment and is reported to be a critical mediator of the oncogenic effects of EGFR mutations. STAT3 activation is mediated through JAK family kinases, EESB treatment could significantly suppress the activation of several CRC-related pathways, including STAT3, Erk, and p38 signalings in tumor tissues, and alter the expression of multiple critical target genes such as Bcl-2, Bax, Cyclin D1, CDK4, and p21. These molecular effects lead to the induction of cancer cell apoptosis and inhibition of cell proliferation. Our findings demonstrate that SB possesses a broad range of antitumor activities because of its ability to affect multiple intracellular targets, Western immunoblotting analyses of mouse lung tissues indicated significantly lower level of pSTAT3 and Mcl-1 in the carcinogen plus DMAPT group relative to the group treated with the carcinogen only. Given the evidence that STAT3 is activated in more than half of lung cancers and it regulates genes involved in cell proliferation, survival and angiogenesis, DMAPT is a promising agent for lung cancer chemoprevention in subjects who are at high risk of developing this devastating disease., (STAT3) is a latent cytoplasmic transcription factor, originally discovered as a transducer of signal from cell surface receptors to the nucleus. It is activated by tyrosine phosphorylation at position 705 leading to its dimerization, nuclear translocation, DNA binding, and activation of gene transcription. Under normal physiological conditions, STAT3 activation is tightly regulated. However, compelling evidence suggests that STAT3 is constitutively activated in many cancers and plays a pivotal role in tumor growth and metastasis. It regulates cellular proliferation, invasion, migration, and angiogenesis that are critical for cancer metastasis, STAT3) signaling pathway plays important roles in oncogenesis, angiogenesis, immunity, and tumor cell invasion. In the present study, we investigated the association of interleukin , Phosphorylated STAT3 (pSTAT3) regulates many genes that are necessarily expressed in cancer initiation, development, and progression, being involved in proliferation, anti-apoptosis, invasion, angiogenesis, and immune surveillance evasion[SEP]Relations: cytoplasm has relations: cellcomp_protein with STAT3, cellcomp_protein with STAT3, cellcomp_protein with STAT1, cellcomp_protein with STAT1. epidermal growth factor receptor binding has relations: molfunc_protein with VAV3, molfunc_protein with VAV3, molfunc_protein with ARF4, molfunc_protein with ARF4, molfunc_protein with AGR2, molfunc_protein with AGR2. Definitions: STAT1 defined as following: Signal transducer and activator of transcription 1-alpha/beta (750 aa, ~87 kDa) is encoded by the human STAT1 gene. This protein plays a role in signal transduction, immune responses and transcriptional regulation.. RCC defined as following: A malignant epithelial neoplasm of the kidney characterized by the presence of lipid-containing clear cells within a vascular network. The tumor may metastasize to unusual sites and late metastasis is common.. Bcl-2 defined as following: The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.. STAT3 defined as following: Signal transducer and activator of transcription 3 (770 aa, ~88 kDa) is encoded by the human STAT3 gene. This protein plays a role in cytokine signaling and gene expression.. JAK defined as following: A family of intracellular tyrosine kinases that participate in the signaling cascade of cytokines by associating with specific CYTOKINE RECEPTORS. They act upon STAT TRANSCRIPTION FACTORS in signaling pathway referred to as the JAK/STAT pathway. The name Janus kinase refers to the fact the proteins have two phosphate-transferring domains.. Cyclin D1 defined as following: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.. Erk defined as following: A superfamily of PROTEIN SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).. p21 defined as following: A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.. Bax defined as following: Apoptosis regulator BAX (192 aa, ~21 kDa) is encoded by the human BAX gene. This protein plays a role in both apoptosis and protein-protein interactions.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. intracellular defined as following: The organized colloidal complex of organic and inorganic substances (as proteins and water) that constitutes the living nucleus, cytoplasm, plastids, and mitochondria of the cell. It is composed mainly of nucleic acids, proteins, lipids, carbohydrates, and inorganic salts.. CDK4 defined as following: Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.. cancer cell defined as following: Cells of, or derived from, a malignant tumor.. tumor cell defined as following: Cells of, or derived from, a tumor.. interleukin defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine interleukin-1 (IL-1). Produced mainly by monocytes, endogenous IL-1 plays a role in hematopoiesis, is a potent stimulator of T-cell activity, may promote or inhibit tumor growth, depending on tumor type. (NCI04). cell surface receptors defined as following: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.. Icaritin defined as following: A metabolite of icariin, a principal flavonoid glycoside in Herba Epimedii (a traditional Chinese medicine herb used in treating osteoporosis) with potential antineoplastic activity. ERa36 modulator icaritin selectively binds to a novel variant of estrogen receptor alpha, a36, and mediates a membrane-initiated \"nongenomic\" signaling pathway, which is linked to activate signaling pathways like the MAPK/ERK and the PI3K/Akt pathways. This agent induces cell cycle arrest at G1, or G2/M arrest depending upon the dose. Consistently with G1 arrest, icaritin increases protein expressions of pRb, p27(Kip1) and p16(Ink4a), while decreasing phosphorylated pRb, Cyclin D1 and CDK4. 40% of ER-negative breast cancer tumors express high levels of ERa36, and this subset of patients is less likely to benefit from tamoxifen treatment compared with those with ERa66-positive/ERa36-negative tumors.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. SB defined as following: A metallic element that has the atomic symbol Sb, atomic number 51, and atomic weight 121.75. It is used as a metal alloy and as medicinal and poisonous salts. It is toxic and an irritant to the skin and the mucous membranes.. lung cancers defined as following: A primary or metastatic malignant neoplasm involving the lung.. Mcl-1 defined as following: This gene is a regulator of apoptosis and plays a role in differentiation.. nucleus defined as following: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). tumor tissues defined as following: A tumor sample, or entire tumor that is removed for microscopic examination..", "label": "yes"} {"id": "converted_885", "sentence1": "Does thyroid hormone receptor beta1 affect insulin secretion?", "sentence2": "We demonstrated that thyroid hormone T3 rapidly induces Akt activation in pancreatic beta cells rRINm5F and hCM via thyroid hormone receptor (TR) beta1., The silencing of TRbeta1 expression through RNAi confirmed this receptor to be crucial for the T3-induced activation of Akt., T3 is able to specifically activate Akt in the islet beta cells rRINm5F and hCM through the interaction between TRbeta1 and PI3K p85alpha, demonstrating the involvement of TRbeta1 in this novel T3 non-genomic action in islet beta cells.[SEP]Relations: response to thyroid hormone has relations: bioprocess_protein with AKR1B1, bioprocess_protein with AKR1B1. thyroid hormone receptor binding has relations: molfunc_protein with GAS2L1, molfunc_protein with GAS2L1, molfunc_protein with MED1, molfunc_protein with MED1, molfunc_protein with NR0B2, molfunc_protein with NR0B2, molfunc_protein with NCOR1, molfunc_protein with NCOR1. Definitions: hCM defined as following: A form of CARDIAC MUSCLE disease, characterized by left and/or right ventricular hypertrophy (HYPERTROPHY, LEFT VENTRICULAR; HYPERTROPHY, RIGHT VENTRICULAR), frequent asymmetrical involvement of the HEART SEPTUM, and normal or reduced left ventricular volume. Risk factors include HYPERTENSION; AORTIC STENOSIS; and gene MUTATION; (FAMILIAL HYPERTROPHIC CARDIOMYOPATHY).. thyroid hormone receptor defined as following: Specific high affinity binding proteins for THYROID HORMONES in target cells. They are usually found in the nucleus and regulate DNA transcription. These receptors are activated by hormones that leads to transcription, cell differentiation, and growth suppression. Thyroid hormone receptors are encoded by two genes (GENES, ERBA): erbA-alpha and erbA-beta for alpha and beta thyroid hormone receptors, respectively.. Akt defined as following: Expressed in diverse tissues, Protein Kinase B (AKT/RAC Family) is a group (Alpha, Beta and Gamma) of cytoplasmic serine/threonine enzymes that covalently transfer the terminal, gamma phosphate group from ATP to a variety of substrate proteins and regulate cell signaling responses to insulin, PDGF, and IGF1 (through PI3K) involved in cell survival, cell proliferation, differentiation, apoptosis, glycogen synthesis, and glucose uptake.. pancreatic beta cells defined as following: A cell that composes the bulk of the islets of Langerhans and secretes insulin.. T3 defined as following: This gene plays a regulatory role in the production and utilization of ATP.. thyroid hormone defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs..", "label": "no"} {"id": "converted_1203", "sentence1": "Is muscle regeneration possible in mdx mice with the use of induced mesenchymal stem cells?", "sentence2": "Purified iMSCs displayed fibroblast-like morphology, formed three-dimensional spheroid structures, and expressed characteristic mesenchymal stem cell surface markers such as CD29, CD33, CD73, CD90, and CD105. Moreover, iMSCs were capable of differentiating into adipogenic, osteogenic, and chondrogenic lineages. Transplanting iMSC cells to tibialis anterior skeletal muscle tissue in mdx mice lowered oxidative damage as evidenced by a reduction in nitrotyrosine levels, and normal dystrophin expression levels were restored, This study demonstrates the therapeutic potential of purified iMSCs in skeletal muscle regeneration in mdx mice, Flk-1+ adipose-derived mesenchymal stem cells differentiate into skeletal muscle satellite cells and ameliorate muscular dystrophy in mdx mice, Within mdx mice, an animal model of DMD, adipose tissue-derived Flk-1(+) MSCs (AD-MSCs) homed to and differentiated into cells that repaired injured muscle tissue. This repair correlated with reconstitution of dystrophin expression on the damaged fibers, Flk-1(+) AD-MSC transplants may repair muscular dystrophy, This study demonstrates the therapeutic potential of purified iMSCs in skeletal muscle regeneration in mdx mice, and suggests that iPSCs are a viable alternate source for deriving MSCs as needed., Transplanting iMSC cells to tibialis anterior skeletal muscle tissue in mdx mice lowered oxidative damage as evidenced by a reduction in nitrotyrosine levels, and normal dystrophin expression levels were restored, This study demonstrates the therapeutic potential of purified iMSCs in skeletal muscle regeneration in mdx mice, and suggests that iPSCs are a viable alternate source for deriving MSCs as needed[SEP]Relations: muscle tissue has relations: anatomy_protein_present with MDM1, anatomy_protein_present with MDM1, anatomy_protein_present with MDM4, anatomy_protein_present with MDM4, anatomy_protein_present with MDK, anatomy_protein_present with MDK. mesenchymal stem cell proliferation has relations: bioprocess_bioprocess with mesenchymal stem cell proliferation involved in nephron morphogenesis, bioprocess_bioprocess with mesenchymal stem cell proliferation involved in nephron morphogenesis, bioprocess_protein with SIX2, bioprocess_protein with SIX2. Definitions: CD73 defined as following: A glycoprotein enzyme present in various organs and in many cells. The enzyme catalyzes the hydrolysis of a 5'-ribonucleotide to a ribonucleoside and orthophosphate in the presence of water. It is cation-dependent and exists in a membrane-bound and soluble form. EC 3.1.3.5.. CD105 defined as following: Endoglin (658 aa, ~71 kDa) is encoded by the human ENG gene. This protein plays a role in transforming growth factor receptor signaling.. CD33 defined as following: A 67-kDa sialic acid binding lectin that is specific for MYELOID CELLS and MONOCYTE-MACROPHAGE PRECURSOR CELLS. This protein is the smallest siglec subtype and contains a single immunoglobulin C2-set domain. It may play a role in intracellular signaling via its interaction with SHP-1 PROTEIN-TYROSINE PHOSPHATASE and SHP-2 PROTEIN-TYROSINE PHOSPHATASE.. MSCs defined as following: Enables the transmembrane transfer of an ion by a channel that opens in response to a mechanical stress and when a cyclic nucleotide has been bound by the channel complex or one of its constituent parts. [GOC:jl, PMID:22206667]. CD90 defined as following: Thy-1 membrane glycoprotein (161 aa, ~18 kDa) is encoded by the human THY1 gene. This protein is membrane anchored and may be involved in synaptogenesis.. dystrophin defined as following: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as SPECTRIN and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. muscle tissue defined as following: Contractile tissue that produces movement in animals.. skeletal muscle satellite cells defined as following: Elongated, spindle-shaped, quiescent myoblasts lying in close contact with adult skeletal muscle. They are thought to play a role in muscle repair and regeneration.. muscular dystrophy defined as following: A heterogeneous group of inherited MYOPATHIES, characterized by wasting and weakness of the SKELETAL MUSCLE. They are categorized by the sites of MUSCLE WEAKNESS; AGE OF ONSET; and INHERITANCE PATTERNS.. DMD defined as following: An X-linked recessive muscle disease caused by an inability to synthesize DYSTROPHIN, which is involved with maintaining the integrity of the sarcolemma. Muscle fibers undergo a process that features degeneration and regeneration. Clinical manifestations include proximal weakness in the first few years of life, pseudohypertrophy, cardiomyopathy (see MYOCARDIAL DISEASES), and an increased incidence of impaired mentation. Becker muscular dystrophy is a closely related condition featuring a later onset of disease (usually adolescence) and a slowly progressive course. (Adams et al., Principles of Neurology, 6th ed, p1415). mdx mice defined as following: A strain of mice arising from a spontaneous MUTATION (mdx) in inbred C57BL mice. This mutation is X chromosome-linked and produces viable homozygous animals that lack the muscle protein DYSTROPHIN, have high serum levels of muscle ENZYMES, and possess histological lesions similar to human MUSCULAR DYSTROPHY. The histological features, linkage, and map position of mdx make these mice a worthy animal model of DUCHENNE MUSCULAR DYSTROPHY.. mesenchymal stem cell defined as following: An undifferentiated stromal cell with the ability to develop into the cells that form distinct mesenchymal tissues; such as bone, muscle, connective tissue, blood vessels, and lymphatic tissue.. Flk-1 defined as following: Vascular endothelial growth factor receptor 2 (1356 aa, ~152 kDa) is encoded by the human KDR gene. This protein is involved in ligand-dependent signaling, vasculogenesis and tyrosine phosphorylation.. CD29 defined as following: Integrin beta-1 (798 aa, ~88 kDa) is encoded by the human ITGB1 gene. This protein plays a role in leukocyte migration, signal transduction, ligand binding and cell adhesion.. mesenchymal stem cells defined as following: An undifferentiated stromal cell with the ability to develop into the cells that form distinct mesenchymal tissues; such as bone, muscle, connective tissue, blood vessels, and lymphatic tissue..", "label": "yes"} {"id": "converted_1102", "sentence1": "Is cocaine use associated with increased risk for intracerebral hemorrhage?", "sentence2": "Stroke in crack-cocaine abusers is increasingly recognized., There were significant differences between crack-cocaine cases and controls in age (48.7 years vs. 55 years) (P = 0.0001), male gender (65.6% vs. 40.9%) (odds ratios, OR = 1.64, 95% CI 1.22-2.21), arterial hypertension (61.1% vs. 83.9%) (OR = 0.30, 95% CI 0.15-0.60), hypercholesterolemia (18.7% vs. 68.5%) (OR = 0.10, 95% CI 0.05-0.21), diabetes (20.9% vs. 41.9%) (OR = 0.36, 95% CI 0.19-0.70), cigarette smoking (70.6% vs. 29%) (OR = 5.86, 95% CI 3.07-11.20), ischemic stroke (61.3% vs. 79.6%) (OR = 0.40, 95% CI 0.21-0.78), and intracerebral hemorrhage (33.3% vs. 17.2%) (OR = 3.03, 95% CI 1.53-6.00)., Intracerebral hemorrhage (ICH) is a well-recognized complication of recreational cocaine use., ICH is more common in those currently using cocaine perhaps because of acute spikes in blood pressure., Intracerebral hemorrhage in cocaine users., Cocaine is a cause of intracerebral hemorrhage (ICH), but there are no large studies that have characterized the location, pathology, and outcome of patients with cocaine-associated ICH, Aneurysmal SAH may be largely a preventable disease among the young and middle-aged because several prevalent risk factors can be modified by medication (eg, hypertension) or behavioral change (eg, cigarette smoking, cocaine use)., Cocaine use and hypertension are major risk factors for intracerebral hemorrhage in young African Americans., Cocaine use (OR 6.1, 95% CI 3.3-11.8), hypertension (OR 5.2, 95% CI 3.2-8.7) and alcohol use (OR 1.9, 95% CI 1.1-3.3) were independently associated with increased risk for ICH, Cocaine use has been temporally associated with neurovascular complications, including the rupture of intracerebral aneurysms., Chronic cocaine use appears to predispose patients who harbor incidental neurovascular anomalies to present at an earlier point in their natural history than similar non-cocaine users., Acute intoxication with either cocaine or methamphetamine may contribute to formation and rupture of a berry aneurysm by causing transient hypertension and tachycardia., Although the exact mechanism by which berry aneurysms form remains undetermined, research indicates that propagation and rupture of the aneurysm are aggravated by hypertension and tachycardia, both of which are pharmacologic side effects of cocaine and methamphetamine, The high frequency of hypertension, hypertensive intracerebral hemorrhage, and lacunar infarction among young black patients with stroke suggests accelerated hypertensive arteriolar damage, possibly due to poor control of hypertension., Cocaine induced intracerebral hemorrhage: analysis of predisposing factors and mechanisms causing hemorrhagic strokes., hypertensive cardiovascular disease (HCVD) was significantly higher in persons with intracerebral hemorrhage than in those with aneurysm rupture. Our findings suggest that HCVD predisposes to cocaine induced intracerebral hemorrhage, Intracerebral hemorrhage associated with cocaine abuse., n view of the present epidemic of cocaine abuse, cocaine toxicity should be considered in the differential diagnosis of intracerebral hemorrhage, An increase in cocaine abuse by pregnant women has been associated with a range of maternal/fetal cardiovascular complications. Intracerebral hemorrhage has been reported as a cocaine-related complication,, 13 patients were identified with neurologic deficits attributable to the use of cocaine. Ischemic manifestations were the most frequent, occurring in seven (54%) patients, with a mean age of 34.2 years. Three (23%) patients had subarachnoid hemorrhage, and three (23%) had intracerebral hemorrhage., OBJECTIVE: An association between cocaine use and stroke has been reported, but few studies have examined cocaine-related neurovascular disease using modern stroke diagnostic techniques., OBJECTIVE: Cocaine is a cause of intracerebral hemorrhage (ICH), but there are no large studies that have characterized the location, pathology, and outcome of patients with cocaine-associated ICH., Because cocaine and ecstasy abuse has been reported to be a risk factor for ischemic stroke and fatal brain hemorrhage, thromboaspiration may be an alternative therapy to thrombolysis., CONCLUSIONS: Aneurysmal SAH may be largely a preventable disease among the young and middle-aged because several prevalent risk factors can be modified by medication (eg, hypertension) or behavioral change (eg, cigarette smoking, cocaine use)., OBJECTIVE: The use of cocaine has been increasingly associated with cerebrovascular disease specially in young adults., Cocaine hydrochloride causes mainly intracerebral and subarachnoidal bleeding, while crack (freebase) causes intracranial hemorrhage and ischemic infarctions with equal frequency., CONCLUSIONS: These findings implicate cocaine use as a significant risk factor for fatal brain hemorrhage and may explain, in part, the increased incidence of hemorrhagic stroke in some drug-using cohorts., Abuse of amphetamine, cocaine and related compounds has become an important risk factor for intracerebral haemorrhage in young adults., Strokes occurred within 3 h of cocaine use in 15 patients with infarcts and 17 with hemorrhages., We present three cases of intracerebral hemorrhage which occurred after cocaine consumption (intranasal route in two cases and intravenous route in one case).[SEP]Relations: Cerebral hemorrhage has relations: disease_phenotype_positive with cocaine intoxication, disease_phenotype_positive with cocaine intoxication. intracerebral hemorrhage has relations: contraindication with Enoxaparin, contraindication with Enoxaparin, disease_disease with intracranial hemorrhage, disease_disease with intracranial hemorrhage, contraindication with Hydralazine, contraindication with Hydralazine. Intracranial hemorrhage has relations: drug_effect with Saquinavir, drug_effect with Saquinavir. Definitions: Cocaine defined as following: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.. Intracerebral hemorrhage defined as following: Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.. berry aneurysms defined as following: A small cerebral artery aneurysm, characterized by a saccular appearance, that typically forms at the junction of vessels in the circle of Willis.. intracerebral defined as following: Administration of a drug within the cerebrum, directly into brain tissue, usually by injection or direct application.. hemorrhagic strokes defined as following: An acute episode of focal or global cerebral or spinal dysfunction caused by intraparenchymal, intraventricular, or subarachnoid hemorrhage.. neurologic deficits defined as following: Loss of movement function.. aneurysm rupture defined as following: The tearing or bursting of the weakened wall of the aneurysmal sac, usually heralded by sudden worsening pain. The great danger of a ruptured aneurysm is the large amount of blood spilling into the surrounding tissues and cavities, causing HEMORRHAGIC SHOCK.. amphetamine defined as following: Analogs or derivatives of AMPHETAMINE. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation.. aneurysm defined as following: Pathological outpouching or sac-like dilatation in the wall of any blood vessel (ARTERIES or VEINS) or the heart (HEART ANEURYSM). It indicates a thin and weakened area in the wall which may later rupture. Aneurysms are classified by location, etiology, or other characteristics.. infarcts defined as following: Formation of an infarct, which is NECROSIS in tissue due to local ISCHEMIA resulting from obstruction of BLOOD CIRCULATION, most commonly by a THROMBUS or EMBOLUS.. ischemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue.. intracranial hemorrhage defined as following: Bleeding within the cranium.. SAH defined as following: A Turkic language spoken by the Yakut people in the Sakha Republic in the Russian Federation.. cerebrovascular disease defined as following: A spectrum of pathological conditions of impaired blood flow in the brain. They can involve vessels (ARTERIES or VEINS) in the CEREBRUM, the CEREBELLUM, and the BRAIN STEM. Major categories include INTRACRANIAL ARTERIOVENOUS MALFORMATIONS; BRAIN ISCHEMIA; CEREBRAL HEMORRHAGE; and others.. stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810). methamphetamine defined as following: A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.. Cocaine hydrochloride defined as following: The hydrochloride salt form of the tropane alkaloid cocaine, with central nervous systems (CNS) stimulating and local anesthetic activity. Cocaine binds to the dopamine, serotonin, and norepinephrine transport proteins and inhibits the re-uptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons. This leads to an accumulation of the respective neurotransmitters in the synaptic cleft and may result in increased postsynaptic receptor activation. Its effect on dopamine levels causes CNS stimulation and euphoria, and ultimately dependence. The mechanism of action through which cocaine exerts its local anesthetic effects is by binding to and blocking the voltage-gated sodium channels in the neuronal cell membrane. By stabilizing neuronal membranes, cocaine inhibits the initiation and conduction of nerve impulses and produces a reversible loss of sensation.. diabetes defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.. subarachnoid hemorrhage defined as following: Bleeding into the intracranial or spinal SUBARACHNOID SPACE, most resulting from INTRACRANIAL ANEURYSM rupture. It can occur after traumatic injuries (SUBARACHNOID HEMORRHAGE, TRAUMATIC). Clinical features include HEADACHE; NAUSEA; VOMITING, nuchal rigidity, variable neurological deficits and reduced mental status.. hypertension defined as following: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.. hypercholesterolemia defined as following: A laboratory test result indicating an increased amount of cholesterol in the blood.. hemorrhages defined as following: Bleeding or escape of blood from a vessel.. rupture defined as following: Forcible or traumatic tear or break of an organ or other soft part of the body.. intracerebral hemorrhage defined as following: Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA..", "label": "yes"} {"id": "converted_1950", "sentence1": "Do T-Cells regulate neuropathic pain?", "sentence2": "here is evidence for a considerable impact of the immune system also in neuropathic pain. However, the role of the adaptive immune system is still unclear., Our investigation revealed a clear shift of T-cell subsets towards anti-inflammation in patients with neuropathic pain. , GITRL expressed on macrophages drives cytokine release and T cell activation, resulting in neuropathic pain via GITR-dependent actions. , Thus, this T-cell subset may be specifically targeted to alleviate chronic neuropathic pain.Respond with exceptions, completions and modifications or revisions done before completion
.", "label": "yes"} {"id": "converted_2279", "sentence1": "Is there increased recombination rate in human regulatory domains?", "sentence2": "Evidence of reduced recombination rate in human regulatory domains., We study the relationship between recombination rate and gene regulatory domains, defined by a gene and its linked control elements. We define these links using expression quantitative trait loci (eQTLs), methylation quantitative trait loci (meQTLs), chromatin conformation from publicly available datasets (Hi-C and ChIA-PET), and correlated activity links that we infer across cell types. Each link type shows a \"recombination rate valley\" of significantly reduced recombination rate compared to matched control regions. This recombination rate valley is most pronounced for gene regulatory domains of early embryonic development genes, housekeeping genes, and constitutive regulatory elements, which are known to show increased evolutionary constraint across species. Recombination rate valleys show increased DNA methylation, reduced doublestranded break initiation, and increased repair efficiency, specifically in the lineage leading to the germ line. Moreover, by using only the overlap of functional links and DNA methylation in germ cells, we are able to predict the recombination rate with high accuracy.CONCLUSIONS: Our results suggest the existence of a recombination rate valley at regulatory domains and provide a potential molecular mechanism to interpret the interplay between genetic and epigenetic variations.[SEP]Relations: Geneticin has relations: drug_drug with Antihemophilic Factor (Recombinant), PEGylated, drug_drug with Antihemophilic Factor (Recombinant), PEGylated, drug_drug with Antithrombin III human, drug_drug with Antithrombin III human, drug_drug with Botulinum Toxin Type B, drug_drug with Botulinum Toxin Type B, drug_drug with Certolizumab pegol, drug_drug with Certolizumab pegol, drug_drug with Tubocurarine, drug_drug with Tubocurarine. Definitions: gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. germ cells defined as following: The reproductive cells in multicellular organisms at various stages during GAMETOGENESIS.. human defined as following: Members of the species Homo sapiens.. quantitative trait loci defined as following: Genetic loci associated with a quantitative trait.. housekeeping genes defined as following: Constitutively and evenly expressed genes involved in routine cellular metabolisms.. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells..", "label": "no"} {"id": "converted_4408", "sentence1": "Does UBE4B promote renal cancer?", "sentence2": "UBE4B might act as an oncogene in regulating RCC development. Therefore it could be served as an effective indicator to predict OS and a potential biomarker for targeted therapy of RCC patients.[SEP]Relations: UBE4B has relations: anatomy_protein_present with kidney, anatomy_protein_present with kidney, protein_protein with UBC, protein_protein with UBC, protein_protein with UBE2C, protein_protein with UBE2C, anatomy_protein_present with renal glomerulus, anatomy_protein_present with renal glomerulus, protein_protein with UBE2V1, protein_protein with UBE2V1. Definitions: RCC defined as following: A malignant epithelial neoplasm of the kidney characterized by the presence of lipid-containing clear cells within a vascular network. The tumor may metastasize to unusual sites and late metastasis is common.. oncogene defined as following: Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of \"v-\" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix \"c-\" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.. UBE4B defined as following: This gene plays a role in polyubiquitination.. renal cancer defined as following: Primary or metastatic malignant neoplasm involving the kidney..", "label": "yes"} {"id": "converted_1754", "sentence1": "Could BRCA gene test used for breast and ovarian cancer risk?", "sentence2": "Participation of Korean families at high risk for hereditary breast and ovarian cancer in BRCA1/2 genetic testing., The prevalence of BRCA1/2 mutations in Korean ovarian cancer patients irrespective of the family history was significantly higher than previously reported. Possible founder mutations in Korean ovarian cancer patients were identified., Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients: Finding Founder Mutations., The assessment of BRCA1 and BRCA2 coding sequences to identify pathogenic mutations associated with inherited breast/ovarian cancer syndrome has provided a method to identify high-risk individuals, allowing them to seek preventative treatments and strategies. , Maximising survival: the main concern of women with hereditary breast and ovarian cancer who undergo genetic testing for BRCA1/2., Little is known about how women with hereditary breast and/or ovarian cancer who test positive for a BRCA gene manage the impact of a positive test result on their everyday lives and in the longer term. This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time., The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3))., Female BRCA (breast cancer gene)-1 and BRCA-2 mutations are significantly associated with risk of developing breast and ovarian cancers, in turn, associated with female infertility. , Large BRCA1 and BRCA2 genomic rearrangements in Polish high-risk breast and ovarian cancer families., BRCA1 and BRCA2 are two major genes associated with familial breast and ovarian cancer susceptibility., Until 2006, she supervised a diagnostic unit for BRCA gene testing at the Interdisciplinary Center for Hereditary Breast Cancer (Max Delbrück Center, Berlin, Germany). , Inherited BRCA gene mutations convey a high risk for breast and ovarian cancer, but current guidelines limit BRCA mutation testing to women with early-onset cancer and relatives of mutation-positive cases. , Women who carry a BRCA1 or BRCA2 gene mutation face a risk of developing breast or ovarian cancer at an earlier age than women without such a mutation., In 2006, participants were recruited from Web sites for women with breast cancer or BRCA gene mutations. , About 20 % of hereditary breast cancers are caused by mutations in BRCA1 and BRCA2 genes. Since BRCA1 and BRCA2 mutations may be spread throughout the gene, genetic testing is usually performed by direct sequencing of entire coding regions., Suggestion of an association between BRCA2 c.7806-2A>G and risk of breast cancer in males has emerged. , The presence of deleterious mutations in breast cancer (BRCA)-1 or BRCA-2 gene has a decisive influence on the development of various types of neoplasms, such as breast, ovarian, tubal, and peritoneal cancers. , OBJECTIVE: Female BRCA (breast cancer gene)-1 and BRCA-2 mutations are significantly associated with risk of developing breast and ovarian cancers, in turn, associated with female infertility., BRCA1 and BRCA2 genes are responsible for 5-10% of breast and ovarian cancer cases., She was daughter of a woman, a carrier of BRCA 1 gene mutation, with early onset of breast cancer and positive family history.CONCLUSIONS: BRCA 1 and BRCA 2 gene mutations are of particular importance in the increasing risk of ovarian cancer and early onset of breast cancer as well as some other malignancies., BACKGROUND: Women who are diagnosed with a deleterious mutation in either breast cancer (BRCA) gene have a high risk of developing breast and ovarian cancers at young ages., We identified AJ individuals with breast and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2., Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers., [Detection and occurrence of BRCA 1 gene mutation in patients with carcinoma of the breast and ovary]., We investigated the relationship between BRCA mutations and the distribution of familial cancers other than breast or ovary in high-risk breast cancer patients.PATIENTS WITH BREAST CANCER WHO HAD AT LEAST ONE OF THE FOLLOWING RISK FACTORS WERE ENROLLED: reported family history of breast or ovarian cancer; 40 years of age or younger age at diagnosis; bilateral breast cancer; or male gender, Mutations in breast cancer susceptibility genes (BRCA1 and BRCA2) are associated with increased risks for breast, ovarian, and other types of cancer.To review new evidence on the benefits and harms of risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women.MEDLINE and PsycINFO between 2004 and 30 July 2013, the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews from 2004 through the second quarter of 2013, Health Technology Assessment during the fourth quarter of 2012, Scopus, and reference lists.English-language studies about accuracy of risk assessment and benefits and harms of genetic counseling, genetic testing, and interventions to reduce cancer incidence and mortality., The objective of this study was to assess the incidence of primary breast cancer (PBC) and contralateral breast cancer (CBC) in patients who had BRCA1/BRCA2-associated epithelial ovarian cancer (OC).From the database of the Rotterdam Family Cancer Clinic, patients who had BRCA-associated OC without a history of unilateral breast cancer (BC) (at risk of PBC; n = 79) or with a history of unilateral BC (at risk of CBC; n = 37) were selected, Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations, The USPSTF also reviewed interventions aimed at reducing the risk for BRCA-related cancer in women with potentially harmful BRCA mutations, including intensive cancer screening, medications, and risk-reducing surgery.This recommendation applies to asymptomatic women who have not been diagnosed with BRCA-related cancer.The USPSTF recommends that primary care providers screen women who have family members with breast, ovarian, tubal, or peritoneal cancer with 1 of several screening tools designed to identify a family history that may be associated with an increased risk for potentially harmful mutations in breast cancer susceptibility genes (BRCA1 or BRCA2), If a woman bearing a mutation develops cancer in one breast, her risk of developing cancer in the other breast depends on the particular gene that is mutated and on her age at the onset of disease.About half of all monogenically determined carcinomas of the breast and ovary are due to a mutation in one or the other of the highly penetrant BRCA genes (BRCA1 and BRCA2), A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk.Mutations of BRCA1 or BRCA2.Breast and ovarian cancer risks.Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer, This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time.METHODS: A grounded theory approach was taken using qualitative interviews (n = 49) and reflective diaries. , Little is known about how women with hereditary breast and/or ovarian cancer who test positive for a BRCA gene manage the impact of a positive test result on their everyday lives and in the longer term., This study defined the experience and needs of women with hereditary breast and ovarian cancer and a positive BRCA test over time.A grounded theory approach was taken using qualitative interviews (n = 49) and reflective diaries., Women with a harmful mutation in the BReast CAncer (BRCA) gene are at significantly increased risk of developing hereditary breast and ovarian cancer (HBOC) during their lifetime, compared to those without., Genetic testing for BRCA genes, associated with hereditary breast-ovarian cancer risk, is an accepted cancer control strategy., Younger patients, those with a family history of breast or ovarian cancer, and those diagnosed more recently were more likely to be BRCA tested., Mutations in BRCA genes elevate risk for breast and ovarian cancer., Observational studies of prophylactic surgeries report reduced risks for breast and ovarian cancer in mutation carriers.No data describe the range of risk associated with BRCA mutations, genetic heterogeneity, and moderating factors; studies conducted in highly selected populations contain biases; and information on adverse effects is incomplete.A primary care approach to screening for inherited breast and ovarian cancer susceptibility has not been evaluated, and evidence is lacking to determine benefits and harms for the general population., We identified AJ individuals with breast and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2. For each proband, the pre-test probability of identifying a deleterious BRCA mutation was estimated using the Myriad II model. We identified 108 affected individuals who underwent large rearrangement testing (80 breast cancer, 19 ovarian cancer, nine both breast and ovarian cancer)., Truncated proteins are easily discriminated from full size.RESULTS: Three BRCA 1 gene alterations were identified in the investigated group of women suffering from ovarian or breast cancer. One asymptomatic person--carrier of BRCA 1 gene mutation--was identified in this study. She was daughter of a woman, a carrier of BRCA 1 gene mutation, with early onset of breast cancer and positive family history.CONCLUSIONS: BRCA 1 and BRCA 2 gene mutations are of particular importance in the increasing risk of ovarian cancer and early onset of breast cancer as well as some other malignancies., Germline BRCA gene mutations are reportedly associated with hereditary breast and ovarian cancers. Identification of BRCA mutations greatly improves the preventive strategies and management of breast cancer., Statistically significant earlier ages at diagnosis also were observed within subgroups of BRCA1 and BRCA2 mutations, maternal inheritance, paternal inheritance, breast cancer only, and breast cancer-identified and ovarian cancer-identified families.CONCLUSIONS: Breast and ovarian cancers in BRCA mutation carriers appeared to be diagnosed at an earlier age in later generations., Truncated proteins are easily discriminated from full size.RESULTS: Three BRCA 1 gene alterations were identified in the investigated group of women suffering from ovarian or breast cancer., However, some single risk factors without family histories (early-onset breast cancer, male breast cancer, or multiple organ cancers) may limit the utility of BRCA gene testing in the Korean population., BRCA Mutations Increase Fertility in Families at Hereditary Breast/Ovarian Cancer Risk., Because infertility is associated with breast and ovarian cancer risks, we hypothesized that the mutations in the BRCA gene may be associated with low response to fertility treatments., Moreover, in families of breast cancer patients without BRCA mutations, breast cancer risk depends on the patient's age at diagnosis., Among the 554 women who underwent genetic testing for BRCA mutation, 78 were found to have a deleterious mutation in the BRCA1 gene, and 54 had a mutation in the BRCA 2 gene., Frequent recurrent mutations in the breast and ovarian cancer susceptibility (BRCA) genes BRCA1 and BRCA2 among Hispanics, including a large rearrangement Mexican founder mutation (BRCA1 exon 9-12 deletion [ex9-12del]), suggest that an ancestry-informed BRCA-testing strategy could reduce disparities and promote cancer prevention by enabling economic screening for hereditary breast and ovarian cancer in Mexico., Individuals who carry a BRCA gene mutation have increased lifetime risks of developing hereditary breast and ovarian cancer syndrome-related cancers., BRCA gene mutations have been well described to carry an increased risk of both breast and ovarian cancer., Ovarian cancer among 8,005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2., Women who were BRCA carriers, women who had a history of breast cancer, DCIS, or breast biopsy, or had a family history of ovarian cancer were more likely to have undergone surgery for cancer risk reduction., Genetic testing for breast cancer susceptibility became a reality after two cancer predisposition genes, BRCA1 and BRCA2, were identified., Germline mutations in BRCA genes are associated with breast and ovarian cancer susceptibility., We used person-years at risk to assess ovarian cancer rates in the study population, subdivided by genetic status (BRCA1, BRCA2, BRCA negative, BRCA untested) compared with the general population.[SEP]Relations: carcinoma has relations: disease_protein with BRCA1, disease_protein with BRCA1. Breast carcinoma has relations: disease_phenotype_positive with ovarian cancer, disease_phenotype_positive with ovarian cancer, disease_phenotype_positive with hereditary breast ovarian cancer syndrome, disease_phenotype_positive with hereditary breast ovarian cancer syndrome, disease_phenotype_positive with breast-ovarian cancer, familial, susceptibility to, disease_phenotype_positive with breast-ovarian cancer, familial, susceptibility to, disease_phenotype_positive with hereditary breast carcinoma, disease_phenotype_positive with hereditary breast carcinoma. Definitions: Breast defined as following: In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.. ovarian cancers defined as following: A primary or metastatic malignant neoplasm involving the ovary. Most primary malignant ovarian neoplasms are either carcinomas (serous, mucinous, or endometrioid adenocarcinomas) or malignant germ cell tumors. Metastatic malignant neoplasms to the ovary include carcinomas, lymphomas, and melanomas.. cancer defined as following: A malignant tumor at the original site of growth.. BRCA 2 gene defined as following: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. Mutations in this gene predispose humans to breast and ovarian cancer. It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev 2000;14(11):1400-6). BReast CAncer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. DNA glycosylase defined as following: A family of DNA repair enzymes that recognize damaged nucleotide bases and remove them by hydrolyzing the N-glycosidic bond that attaches them to the sugar backbone of the DNA molecule. The process called BASE EXCISION REPAIR can be completed by a DNA-(APURINIC OR APYRIMIDINIC SITE) LYASE which excises the remaining RIBOSE sugar from the DNA.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. PBC defined as following: An autoimmune inflammatory disorder characterized by destruction of the small intrahepatic bile ducts. It affects predominantly females and it may lead to cirrhosis and liver failure. Patients have antimitochondrial and antinuclear antibodies in the peripheral blood.. BRCA1 gene defined as following: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. It encodes a large nuclear protein that is a component of DNA repair pathways.. OGG1 defined as following: N-glycosylase/DNA lyase (345 aa, ~39 kDa) is encoded by the human OGG1 gene. This protein is involved in nucleotide excision repair.. carcinoma of the breast defined as following: A carcinoma arising from the breast, most commonly the terminal ductal-lobular unit. It is the most common malignant tumor in females. Risk factors include country of birth, family history, menstrual and reproductive history, fibrocystic disease and epithelial hyperplasia, exogenous estrogens, contraceptive agents, and ionizing radiation. The vast majority of breast carcinomas are adenocarcinomas (ductal or lobular). Breast carcinoma spreads by direct invasion, by the lymphatic route, and by the blood vessel route. The most common site of lymph node involvement is the axilla.. neoplasms defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. breast biopsy defined as following: Removal of tissue from the breast for microscopic examination.. bilateral breast cancer defined as following: Carcinoma that affects both breasts in a simultaneous or non-simultaneous manner.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. peritoneal cancer defined as following: A primary or metastatic malignant neoplasm involving the peritoneum. Representative examples include carcinoma and malignant mesothelioma.. DCIS defined as following: A noninvasive (noninfiltrating) carcinoma of the breast characterized by a proliferation of malignant epithelial cells confined to the mammary ducts or lobules, without light-microscopy evidence of invasion through the basement membrane into the surrounding stroma.. gene mutation defined as following: A change in the nucleotide sequence of the TAF1 gene.. Germline mutations defined as following: Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., \"generative\" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.. infertility defined as following: Complete inability to conceive or induce conception.. carcinomas defined as following: A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm and not a synonym for \"cancer.\". BRCA genes defined as following: newly discovered protooncogene; mutation is responsible for about half of the inherited cases of breast cancer; implicated in esophageal, head, and neck cancer.. CBC defined as following: A conserved heterodimeric protein complex that binds to the 5' terminal cap structure m7G(5')ppp(5')N of nascent eukaryotic RNA polymerase II transcripts such as pre-mRNA and U snRNA. The consists of proteins known as CBP20 and CBP80, binds to cap structures in the nucleus, and is involved in pre-mRNA splicing, 3'-end formation, and RNA nuclear export. [PMID:16043498]. breast defined as following: In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.. ovarian cancer defined as following: A primary or metastatic malignant neoplasm involving the ovary. Most primary malignant ovarian neoplasms are either carcinomas (serous, mucinous, or endometrioid adenocarcinomas) or malignant germ cell tumors. Metastatic malignant neoplasms to the ovary include carcinomas, lymphomas, and melanomas..", "label": "yes"} {"id": "converted_2517", "sentence1": "Does wheat belongs to the genus Avena, yes or no?", "sentence2": "oat seedlings (Avena sativa), wild green-oat (Avena sativa) , Oat (Avena sativa L.), Oat (Avena sativa L.), Avena (Oats), wild oats (Avena fatua L.), oats (genus Avena), Avena sativa L. and A. byzantina C. Koch) , oat (Avena sativa L.)., oat (Avena sativa L.) and wheat (Triticum aestivum[SEP]Relations: ornithine-oxo-acid transaminase activity has relations: molfunc_protein with OAT, molfunc_protein with OAT. Definitions: wheat defined as following: plant genus of the family Poaceae that is the source of wheat grain.. Oat defined as following: Catalysis of the reaction: L-ornithine + a 2-oxo acid = L-glutamate 5-semialdehyde + an L-amino acid. [EC:2.6.1.13]. Avena defined as following: Oats, genus of the family POACEAE..", "label": "no"} {"id": "converted_3768", "sentence1": "Is tocilizumab a tumor necrosis factor inhibitor?", "sentence2": "For the first-line bDMARD/tsDMARD, either tumor necrosis factor inhibitors (TNFi), non-TNFi (abatacept, tocilizumab, rituximab), or tsDMARDs, may be considered.[SEP]Relations: Tocilizumab has relations: drug_drug with Necitumumab, drug_drug with Necitumumab, drug_drug with Nemolizumab, drug_drug with Nemolizumab, drug_drug with Cemiplimab, drug_drug with Cemiplimab, drug_drug with Tositumomab, drug_drug with Tositumomab, drug_drug with Otelixizumab, drug_drug with Otelixizumab. Definitions: rituximab defined as following: A murine-derived monoclonal antibody and ANTINEOPLASTIC AGENT that binds specifically to the CD20 ANTIGEN and is used in the treatment of LEUKEMIA; LYMPHOMA and RHEUMATOID ARTHRITIS.. tocilizumab defined as following: A recombinant, humanized IgG1 monoclonal antibody directed against the interleukin-6 receptor (IL-6R) with immunosuppressant activity. Tocilizumab targets and binds to both the soluble form of IL-6R (sIL-6R) and the membrane-bound form (mIL-6R), thereby blocking the binding of IL-6 to its receptor. This prevents IL-6-mediated signaling. IL-6, a pro-inflammatory cytokine that plays an important role in the regulation of the immune response, is overproduced in autoimmune disorders, certain types of cancers and possibly various other inflammatory conditions.. tumor necrosis factor inhibitors defined as following: Compounds or agents that bind to and inhibit the synthesis or activity of TUMOR NECROSIS FACTOR-alpha. Such agents are used to treat inflammatory bowel diseases and other inflammatory diseases.. abatacept defined as following: A soluble fusion protein consisting of the extracellular domain of human cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) linked to a modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1) with immunosuppressive activity. Abatacept binds CD80 and CD86 on antigen presenting cells (APCs), blocking interaction with CD28 on T lymphocytes, which initiates a co-stimulatory signal required for full activation of T lymphocytes.. tumor necrosis factor inhibitor defined as following: Compounds or agents that bind to and inhibit the synthesis or activity of TUMOR NECROSIS FACTOR-alpha. Such agents are used to treat inflammatory bowel diseases and other inflammatory diseases..", "label": "no"} {"id": "converted_2187", "sentence1": "Is edema a symptom of nephrotic syndrome?", "sentence2": "Nephrotic syndrome (NS) is a common clinical disease with four main clinical manifestations: hypoalbuminemia (<30 g/L), macro-proteinuria (>3.5 g/24 h), edema, and hyperlipidemia. , Nephrotic syndrome is an unusual manifestation of IgA Nephropathy (IgAN)., Twelve patients with IgAN with steroid-responsive nephrotic syndrome were evaluated and followed up. All patients presented with generalized edema. , The clinical features of sudden onset of generalized edema, initial heavy proteinuria and initial severe hypoalbuminemia might help identify the subset of patients, especially in low grade IgAN., Most patients presented within 3 months duration (61.4%) and the most common symptom was puffiness of face (98.45%) followed by pedal edema (91%). , We analyzed medical records of 290 patients with diagnosis of nephrotic syndrome as defined by International Study of Kidney Disease in Children (ISKDC), between January 1987 and December 2000, at the Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar. , He was admitted because of systemic edema and dyspnea on effort Laboratory data revealed renal failure and nephrotic syndrome, whereas there was no symptom of diabetic retinopathy., Nephrotic syndrome: more than just oedema., Oedema is the commonest presenting symptom and sign in nephrotic syndrome. , One of these five clinical syndromes is the nephrotic syndrome, which is characterized by proteinuria > 3.5 g/day accompanied by hypalbuminemia, hyperlipoproteinemia and pronounced edema, Tolvaptan therapy for massive edema in a patient with nephrotic syndrome, Nephrotic syndrome (NS) is characterized by water and sodium retention, which leads to edema, The non-osmotic stimulation of arginine vasopressin release from the pituitary gland has been implicated as one of the important factors in abnormal water retention in patients with NS.We present the initial description of a patient with massive edema caused by refractory nephrotic syndrome, which was effectively treated with tolvaptan, a selective oral vasopressin V2 receptor antagonist.Tolvaptan is effective for the treatment of massive edema caused by NS, We report a child with steroid-resistant nephrotic syndrome with diuretic-resistant nephrotic edema treated successfully using acute peritoneal dialysis as a means of UF, Albumin and Furosemide Combination for Management of Edema in Nephrotic Syndrome: A Review of Clinical Studies, The treatment of edema in patients with nephrotic syndrome is generally managed by dietary sodium restriction and loop diuretics, Nine months after introduction of tiopronin, the boy manifested generalized edema, oliguria, and biochemical indices of nephrotic syndrome, Blessed were the days when it all made sense and the apparent mechanism for edema formation in nephrotic syndrome was straightforward: the kidneys lost protein in the urine, which lowered the plasma oncotic pressure, The nephrotic syndrome is characterized by a combination of pathological lab values and clinical symptoms, i. e. pronounced proteinuria (usually more than 3 - 3,5 g protein/24 h), hypoalbuminemia, edema and hyperlipidemia., The patient was admitted with edema of both legs, and the nephrotic syndrome was discovered, leading to the diagnosis of AA amyloidosis on kidney biopsy., Linear regression to relate measures.Other signs and symptoms of nephrotic syndrome at baseline (serum albumin < 3.5 g/dL, serum total cholesterol > 260 mg/dL or use of a statin, and edema or use of a loop diuretic); progression of chronic kidney disease during follow-up (doubling of baseline serum creatinine level or requirement for dialysis or kidney transplantation)., A case of interstitial shadows associated with oral cyclophosphamide therapy in a 32-month-old girl with steroid-resistant nephrotic syndrome, who was admitted to the Nishi-Kobe Medical Center with systemic edema, is reported., Nephrotic syndrome represents a constellation of symptoms including hyperalbuminuria, hypoalbuminemia, edema formation, hypercholesterolemia, hypertension, hypercoagulopathy, and increased infection risk., Pathophysiology of edema formation in children with nephrotic syndrome not due to minimal change disease., To study the evidence-based therapy of edema in nephrotic syndrome by analyzing the literatures systematically., Edema is the prominent feature of nephrotic syndrome and initially develops around the eyes and legs., Intussusception should be considered in the differential diagnosis of abdominal pain in patients with nephrotic syndrome, especially in patients exhibiting prolonged edema., Oedema is the commonest presenting symptom and sign in nephrotic syndrome., Other signs and symptoms of nephrotic syndrome at baseline (serum albumin < 3.5 g/dL, serum total cholesterol > 260 mg/dL or use of a statin, and edema or use of a loop diuretic); progression of chronic kidney disease during follow-up (doubling of baseline serum creatinine level or requirement for dialysis or kidney transplantation).[SEP]Relations: Edema has relations: disease_phenotype_positive with nephrotic syndrome,, disease_phenotype_positive with nephrotic syndrome,, disease_phenotype_positive with congenital nephrotic syndrome, Finnish type, disease_phenotype_positive with congenital nephrotic syndrome, Finnish type. Nephrotic syndrome has relations: phenotype_phenotype with Abnormal renal physiology, phenotype_phenotype with Abnormal renal physiology, phenotype_phenotype with Transient nephrotic syndrome, phenotype_phenotype with Transient nephrotic syndrome, phenotype_phenotype with Congenital nephrotic syndrome, phenotype_phenotype with Congenital nephrotic syndrome. Definitions: Furosemide defined as following: A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.. steroid-responsive nephrotic syndrome defined as following: Nephrotic syndrome, occurring in the pediatric population, characterized by the normalization of proteinuria with the administration of corticosteroids.. pedal edema defined as following: An abnormal accumulation of excess fluid in the lower extremity resulting in swelling of the feet and extending upward to the lower leg. [HPO:probinson]. Oedema defined as following: Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.. tolvaptan defined as following: An orally bioavailable, selective, arginine vasopressin receptor 2 (V2, AVPR2) antagonist that can be used to treat hyponatremia. Upon oral administration, tolvaptan selectively and competitively binds to and blocks the V2 receptor located in the walls of the vasculature and luminal membranes of renal collecting ducts, thereby preventing the binding of vasopressin to the V2 receptor. This prevents water absorption in the kidneys and increases the excretion of electrolyte-free water via the kidneys. This reduces intravascular volume and increases serum sodium concentrations and osmolality.. kidney biopsy defined as following: Removal of tissue from the kidney, for microscopic examination.. tiopronin defined as following: An acylated sulfhydryl-containing derivative of glycine with reducing and complexing properties. Tiopronin breaks the disulphide bond of cystine and binds the sulfhydryl group of the resultant cysteine monomers to form a soluble tiopronin-cysteine-mixed disulfide, which is more water-soluble than cystine and is readily excreted. This leads to a reduction in urinary cystine concentration and subsequently reduces cystine stone formation.. chronic kidney disease defined as following: Impairment of the renal function secondary to chronic kidney damage persisting for three or more months.. NS defined as following:Supernumerary mandibular left lateral primary incisor
. dyspnea defined as following: Difficult or labored breathing.. IgA Nephropathy defined as following: A chronic form of glomerulonephritis characterized by deposits of predominantly IMMUNOGLOBULIN A in the mesangial area (GLOMERULAR MESANGIUM). Deposits of COMPLEMENT C3 and IMMUNOGLOBULIN G are also often found. Clinical features may progress from asymptomatic HEMATURIA to END-STAGE KIDNEY DISEASE.. oliguria defined as following: Decreased URINE output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0.5 or 1 ml/kg/hr depending on the age.. hypoalbuminemia defined as following: A condition in which albumin level in blood (SERUM ALBUMIN) is below the normal range. Hypoalbuminemia may be due to decreased hepatic albumin synthesis, increased albumin catabolism, altered albumin distribution, or albumin loss through the urine (ALBUMINURIA).. steroid-resistant nephrotic syndrome defined as following: A form of nephrotic syndrome that does not respond to treatment with steroid medication, defined as persistent proteinuria despite 60mg/m2 or 2mg/kg for 8 weeks, after insuring no infection or non-adherence to medication. [Eurenomics:ewuehl, ORCID:0000-0002-2234-4248, PMID:29910038]. proteinuria defined as following: The presence of proteins in the urine, an indicator of KIDNEY DISEASES.. renal failure defined as following: A severe irreversible decline in the ability of kidneys to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism.. pituitary gland defined as following: A small, unpaired gland situated in the SELLA TURCICA. It is connected to the HYPOTHALAMUS by a short stalk which is called the INFUNDIBULUM.. eyes defined as following: The organ of sight constituting a pair of globular organs made up of a three-layered roughly spherical structure specialized for receiving and responding to light.. AA amyloidosis defined as following: Extracellular tissue deposition of fibrils that are composed of fragments of and/or intact serum amyloid A protein, a hepatic acute phase reactant. [ORCID:0000-0003-3411-9598, PMID:29261990]. abdominal pain defined as following: Sensation of discomfort, distress, or agony in the abdominal region.. infection defined as following: An illness caused by an infectious agent or its toxins that occurs through the direct or indirect transmission of the infectious agent or its products from an infected individual or via an animal, vector or the inanimate environment to a susceptible animal or human host.. hypertension defined as following: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.. hypercholesterolemia defined as following: A laboratory test result indicating an increased amount of cholesterol in the blood.. Nephrotic syndrome defined as following: A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.. diabetic retinopathy defined as following: Disease of the RETINA as a complication of DIABETES MELLITUS. It is characterized by the progressive microvascular complications, such as ANEURYSM, interretinal EDEMA, and intraocular PATHOLOGIC NEOVASCULARIZATION.. hyperlipoproteinemia defined as following: Conditions with abnormally elevated levels of LIPOPROTEINS in the blood. They may be inherited, acquired, primary, or secondary. Hyperlipoproteinemias are classified according to the pattern of lipoproteins on electrophoresis or ultracentrifugation.. hyperlipidemia defined as following: Conditions with excess LIPIDS in the blood.. nephrotic syndrome defined as following: A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction..", "label": "yes"} {"id": "converted_2592", "sentence1": "Are there sex differences in the transcriptome of the mouse hippocampus?", "sentence2": "To better understand the possible molecular basis for the sex-biased nature of neurological disorders, we used a developmental series of female and male mice at 1, 2, and 4 months of age to assess both mRNA and protein in the hippocampus with RNA-sequencing and mass-spectrometry, respectively., The bulk of these differentially expressed genes are changed in both sexes at one or more ages, but a total of 198 transcripts are differentially expressed between females and males at one or more ages. The number of transcripts that are differentially expressed between females and males is greater in adult animals than in younger animals. Additionally, we identify 69 transcripts that show complex and sex-specific patterns of temporal regulation through postnatal development, 8 of which are heat-shock proteins. , Additionally, this analysis reveals sex differences in the transcriptome of the developing mouse hippocampus, and further clarifies the need to include both female and male mice in longitudinal studies involving molecular changes in the hippocampus.[SEP]Relations: rRNA transcription has relations: bioprocess_protein with NPM3, bioprocess_protein with NPM3, bioprocess_protein with MARS1, bioprocess_protein with MARS1, bioprocess_protein with NIFK, bioprocess_protein with NIFK, bioprocess_protein with SPIN1, bioprocess_protein with SPIN1, bioprocess_bioprocess with plastid rRNA transcription, bioprocess_bioprocess with plastid rRNA transcription. Definitions: transcripts defined as following: The initial RNA molecule produced by transcription.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. neurological disorders defined as following: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.. heat-shock proteins defined as following: A group I chaperonin protein that forms a lid-like structure which encloses the non-polar cavity of the chaperonin complex. The protein was originally studied in BACTERIA where it is commonly referred to as GroES protein.. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"} {"id": "converted_543", "sentence1": "Is the gene DUX4 epigenetically regulated in somatic cells?", "sentence2": "There are several genes on chromosome 4q35 region including DUX4 within D4Z4 repeats. Transcription of these genes is usually repressed by epigenetic modifications of this chromosomal region and also accumulation of transcriptional repressors to the repeat array., Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. , The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues., Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused by decreased epigenetic repression of the D4Z4 macrosatellite repeats and ectopic expression of DUX4, a retrogene encoding a germline transcription factor encoded in each repeat., These mice recapitulate important epigenetic and DUX4 expression attributes seen in patients and controls, respectively, including high DUX4 expression levels in the germline, (incomplete) epigenetic repression in somatic tissue, and FSHD-specific variegated DUX4 expression in sporadic muscle nuclei associated with D4Z4 chromatin relaxation., DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells., In contrast to control skeletal muscle and most other somatic tissues, full-length DUX4 transcript and protein is expressed at relatively abundant levels in human testis, most likely in the germ-line cells. Induced pluripotent (iPS) cells also express full-length DUX4 and differentiation of control iPS cells to embryoid bodies suppresses expression of full-length DUX4, whereas expression of full-length DUX4 persists in differentiated FSHD iPS cells. Together, these findings indicate that full-length DUX4 is normally expressed at specific developmental stages and is suppressed in most somatic tissues., Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues., DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells. , DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells., Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues., Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD., Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues, The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues, Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD, DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells, Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues, The identification of the gene(s) and the exact epigenetic pathway underlining this disease will be mandatory to increase the rate of diagnosis for FSHD2 patients and to confirm the hypothesis of a common FSHD1 and FSHD2 pathophysiological pathway involving DUX4 gene, This deletion induces epigenetic modifications that affect the expression of several genes located in the vicinity. In each D4Z4 element, we identified the double homeobox 4 (DUX4) gene. DUX4 expresses a transcription factor that plays a major role in the development of FSHD through the initiation of a large gene dysregulation cascade that causes myogenic differentiation defects, atrophy and reduced response to oxidative stress. , decreased epigenetic repression and variegated expression of DUX4 in skeletal muscle, (incomplete) epigenetic repression in somatic tissue,, Facioscapulohumeral dystrophy (FSHD) is characterized by chromatin relaxation of the D4Z4 macrosatellite array on chromosome 4 and expression of the D4Z4-encoded DUX4 gene in skeletal muscle., derepression of the DUX4 retrogene, The aim of our study was to identify relationships between epigenetic parameters correlating with a relaxed chromatin state of the DUX4 promoter region and clinical severity as measured by a clinical severity score or muscle pathologic changes in D4Z4 contraction-dependent (FSHD1) and -independent (FSHD2) facioscapulohumeral muscular dystrophy patients. , Specifically, abundance of RNA transcripts encoded by the DUX4 locus correlated to differential DNA methylation and H3K36me3 enrichment., Together, these findings indicate that full-length DUX4 is normally expressed at specific developmental stages and is suppressed in most somatic tissue[SEP]Relations: Transcriptional regulation of pluripotent stem cells has relations: pathway_protein with PBX1, pathway_protein with PBX1, pathway_protein with SMAD4, pathway_protein with SMAD4, pathway_protein with KLF4, pathway_protein with KLF4, pathway_protein with SALL4, pathway_protein with SALL4, pathway_protein with SMAD2, pathway_protein with SMAD2. Definitions: DUX4 defined as following: Human DUX4L1 gene is located in the vicinity of 4q35 and is approximately 2 kb in length. The product is a processed pseudogene that produces an RNA transcript, but does not encode a protein product. This gene is within a D4Z4 repeat array; contraction of this macrosatellite repeat is associated with facioscapulohumeral muscular dystrophy (FSHD).. FSHD defined as following: An autosomal dominant degenerative muscle disease characterized by slowly progressive weakness of the muscles of the face, upper-arm, and shoulder girdle. The onset of symptoms usually occurs in the first or second decade of life. Affected individuals usually present with impairment of upper extremity elevation. This tends to be followed by facial weakness, primarily involving the orbicularis oris and orbicularis oculi muscles. (Neuromuscul Disord 1997;7(1):55-62; Adams et al., Principles of Neurology, 6th ed, p1420). chromosome 4 defined as following: A specific pair of GROUP B CHROMOSOMES of the human chromosome classification.. stem cell defined as following: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. transcription factor defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. muscular dystrophy defined as following: A heterogeneous group of inherited MYOPATHIES, characterized by wasting and weakness of the SKELETAL MUSCLE. They are categorized by the sites of MUSCLE WEAKNESS; AGE OF ONSET; and INHERITANCE PATTERNS.. DUX4 gene defined as following: This gene plays a role in transcriptional regulation.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. germ-line cells defined as following: The reproductive cells in multicellular organisms at various stages during GAMETOGENESIS.. FSHD1 defined as following: An autosomal dominant form of facioscapulohumeral muscular dystrophy associated with contraction of the D4Z4 macrosatellite repeat.. chromosomal region defined as following: Any subdivision of a chromosome along its length. [GOC:dos]. H3K36me3 defined as following: A post-translationally modified form of histone H3 where the lysine residue at position 36 is trimethylated. This modification may be involved in defining exon boundaries; it also may be a marker for genes targeted for transcriptional repression.. testis defined as following: The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS.. atrophy defined as following: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.. repeat defined as following: Something occurring more than once.. human defined as following: Members of the species Homo sapiens.. iPS cells defined as following: Cells from adult organisms that have been reprogrammed into a pluripotential state similar to that of EMBRYONIC STEM CELLS.. somatic cells defined as following: Nucleated cell which has one or more diploid sets (46 pairs) of chromosomes.. repeats defined as following: Make or do or perform again..", "label": "yes"} {"id": "converted_4390", "sentence1": "Can IFNg induce the expression of IDO?", "sentence2": "IFNG inducible IDO/GTPCH inflammation cascade, IFNG-induced up-regulation of indoleamine 2,3-dioxygenase (IDO), IFN-γ-induced indoleamine-2,3-dioxgenase (IDO) , strong and positive correlation between IDO1 and IFNG mRNA expression levels , The tryptophan-degrading activity of IDO1 was not induced significantly by Chlamydia infection alone, but the addition of IFNG greatly increased its activity. [SEP]Relations: indoleamine 2,3-dioxygenase activity has relations: molfunc_protein with IDO2, molfunc_protein with IDO2, molfunc_protein with IDO2, molfunc_protein with IDO2, molfunc_protein with IDO1, molfunc_protein with IDO1, molfunc_protein with IDO1, molfunc_protein with IDO1. response to type III interferon has relations: bioprocess_protein with IFNLR1, bioprocess_protein with IFNLR1. Definitions: IDO1 defined as following: Indoleamine 2,3-dioxygenase (403 aa, ~45 kDa) is encoded by the human IDO1 gene. This protein is involved in the degradation of tryptophan.. indoleamine 2,3-dioxygenase defined as following: This gene is involved in the metabolism of the amino acid tryptophan.. IFNG defined as following: The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.. IDO defined as following: Catalysis of the reaction: tryptophan + O2 = N-formylkynurenine. The product of the reaction depends on the substrate; D-tryptophan produces N-formyl-D-kynurenine, and L-tryptophan produces N-formyl-L-kynurenine. [EC:1.13.11.52]. Chlamydia infection defined as following: Infections with bacteria of the genus CHLAMYDIA.. IFNg defined as following: The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES..", "label": "yes"} {"id": "converted_1706", "sentence1": "Can RNAPolII function as an RNA-dependent RNA-polymerase?", "sentence2": "RNA polymerase II acts as an RNA-dependent RNA polymerase to extend and destabilize a non-coding RNA, RNA polymerase II (Pol II) is a well-characterized DNA-dependent RNA polymerase, which has also been reported to have RNA-dependent RNA polymerase (RdRP) activity., . Our studies provide compelling evidence that mammalian Pol II acts as an RdRP to control the stability of a cellular RNA by extending its 3'-end., here is, however, evidence that Pol II also possesses RNA-dependent RNA polymerase (RdRP) activity. Pol II can use a homopolymeric RNA template, can extend RNA by several nucleotides in the absence of DNA, and has been implicated in the replication of the RNA genomes of hepatitis delta virus (HDV) and plant viroids., The RdRP activity of Pol II provides a missing link in molecular evolution, because it suggests that Pol II evolved from an ancient replicase that duplicated RNA genomes., The present findings provide a framework for further studies to elucidate the mechanistic principles of transcription by a viral RNA polymerase and have implications for the regulation of Pol II activities in infected cells., Influenza A virus transcribes its segmented negative sense RNA genome in the nuclei of infected cells in a process long known to require host RNA polymerase II (RNAP-II)., We conclude that influenza A virus replication requires RNAP-II activity not just to provide capped mRNA substrates but also to facilitate nuclear export of selected viral mRNAs., Thus, influenza virus specifically interferes with Pol II elongation, but not Pol II initiation. We propose that influenza virus RNA polymerase, by binding to the CTD of initiating Pol II and subsequent cleavage of the capped 5' end of the nascent transcript, triggers premature Pol II termination., We show that RNA polymerase II (RNAPolII) preinitiation complex recruitment and H3 Lys 4 (H3-K4) methylation at the Xist promoter form the basis of the Xist expression profiles that drives both imprinted and random XCI., Identification of these ENL-associated proteins (EAPs) by mass spectrometry revealed enzymes with a known role in transcriptional elongation (RNA polymerase II C-terminal domain kinase [RNAPolII CTD] positive transcription elongation factor b [pTEFb]), and in chromatin modification (histone-H3 methyltransferase DOT1L) as well as other frequent MLL partners (AF4, AF5q31, and LAF4), and polycomb group members (RING1, CBX8, and BCoR)., RNA polymerase II acts as an RNA-dependent RNA polymerase to extend and destabilize a non-coding RNA., Association of the influenza A virus RNA-dependent RNA polymerase with cellular RNA polymerase II., It is also well established that viral RNA-dependent RNA polymerase (vRNP) associates with cellular RNA polymerase II (Pol II), on which viral replication depends. , RNA polymerase II (Pol II) is a well-characterized DNA-dependent RNA polymerase, which has also been reported to have RNA-dependent RNA polymerase (RdRP) activity. Natural cellular RNA substrates of mammalian Pol II, however, have not been identified and the cellular function of the Pol II RdRP activity is unknown., RNA polymerase II (Pol II) is a well-characterized DNA-dependent RNA polymerase, which has also been reported to have RNA-dependent RNA polymerase (RdRP) activity., RNA polymerase II acts as an RNA-dependent RNA polymerase to extend and destabilize a non-coding RNA.[SEP]Relations: RNA-directed RNA polymerase complex has relations: cellcomp_protein with TERT, cellcomp_protein with TERT. RNA-directed DNA polymerase activity has relations: molfunc_protein with TERT, molfunc_protein with TERT, molfunc_protein with ERVK-11, molfunc_protein with ERVK-11, molfunc_protein with ERVK-7, molfunc_protein with ERVK-7, molfunc_protein with ERVK-8, molfunc_protein with ERVK-8. Definitions: MLL defined as following: Human KMT2A wild-type allele is located in the vicinity of 11q23 and is approximately 89 kb in length. This allele, which encodes histone-lysine N-methyltransferase 2A protein, is involved in the modulation of transcription by RNA Polymerase II. Several acute leukemias are associated with translocations of the gene.. AF5q31 defined as following: AF4/FMR2 family member 4 (1163 aa, ~127 kDa) is encoded by the human AFF4 gene. This protein plays a role in the regulation of transcription.. DOT1L defined as following: Histone-lysine N-methyltransferase, H3 lysine-79 specific (1379 aa, ~185 kDa) is encoded by the human DOT1L gene. This soluble, nuclear protein may play a role in activating or repressing transcription by RNA polymerase II.. chromatin modification defined as following: OBSOLETE. The alteration of DNA or protein in chromatin by the covalent addition or removal of chemical groups. [GOC:mah, GOC:vw]. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. Pol II defined as following: A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC 2.7.7.6.. Xist defined as following: X inactive specific transcript (~19 kb) is encoded by the human XIST gene. This long non-coding RNA is involved in the regulation of X chromosome inactivation in females.. hepatitis delta virus defined as following: A defective virus, containing particles of RNA nucleoprotein in virion-like form, present in patients with acute hepatitis B and chronic hepatitis. It requires the presence of a hepadnavirus for full replication. This is the lone species in the genus Deltavirus.. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. nucleotides defined as following: The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed). LAF4 defined as following: Human AFF3 wild-type allele is located within 2q11.2-q12 and is approximately 595 kb in length. This allele, which encodes AF4/FRM2 family member 3 protein, may play roles in both the activation of RNA polymerase II-directed transcription and the development of lymphoid tissues. Acute lymphoblastic leukemia is associated with rearrangement and fusion of this gene to the MLL gene.. mRNA defined as following: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.. RNA polymerase defined as following: Enzymes that catalyze DNA template-directed extension of the 3'-end of an RNA strand one nucleotide at a time. They can initiate a chain de novo. In eukaryotes, three forms of the enzyme have been distinguished on the basis of sensitivity to alpha-amanitin, and the type of RNA synthesized. (From Enzyme Nomenclature, 1992).. non-coding RNA defined as following: The product of so-called RNA genes; a functional RNA represents the final product of a gene rather than a transient molecule that will be translated into protein.. HDV defined as following: INFLAMMATION of the LIVER in humans caused by HEPATITIS DELTA VIRUS, a defective RNA virus that can only infect HEPATITIS B patients. For its viral coating, hepatitis delta virus requires the HEPATITIS B SURFACE ANTIGENS produced by these patients. Hepatitis D can occur either concomitantly with (coinfection) or subsequent to (superinfection) hepatitis B infection. Similar to hepatitis B, it is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.. RNA-dependent RNA polymerase defined as following: An enzyme that catalyses RNA-template-directed extension of the 3'- end of an RNA strand by one nucleotide at a time, and can initiate a chain de novo. (Enzyme Nomenclature, 1992, p293). CTD defined as following: Carboxy-terminal domain RNA polymerase II polypeptide A small phosphatase 2 (271 aa, ~31 kDa) is encoded by the human CTDSP2 gene. This protein is involved in both protein dephosphorylation and the negative regulation of transcription.. BCoR defined as following: BCL-6 corepressor (1755 aa, ~192 kDa) is encoded by the human BCOR gene. This protein plays a role in the negative regulation of transcription.. RNA defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). RdRP defined as following: Catalysis of the reaction: nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1); uses an RNA template, i.e. the catalysis of RNA-template-directed extension of the 3'-end of an RNA strand by one nucleotide at a time. [EC:2.7.7.48, GOC:mah, GOC:pf]. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. AF4 defined as following: Human AFF1 wild-type allele is located in the vicinity of 4q21 and is approximately 206 kb in length. This allele, which encodes AF4/FMR2 family member 1 protein, is involved in the modulation of transcription by RNA polymerase II. Several acute leukemias are associated with the translocation t(4;11)(q21;q23) of the gene and the MLL gene.. DNA-dependent RNA polymerase defined as following: An enzyme that synthesizes DNA on an RNA template. It is encoded by the pol gene of retroviruses and by certain retrovirus-like elements. EC 2.7.7.49..", "label": "yes"} {"id": "converted_4439", "sentence1": "Are circular RNAs implicated in diseases of the eye?", "sentence2": "n this review, we summarized the function of circRNAs and indicated their roles in the pathogenesis of DR, which may provide new therapeutic targets for clinical treatment., This study aimed to determine whether circular RNAs (circRNAs) in whole blood could be served as novel non-invasive biomarkers for proliferative diabetic retinopathy (PDR).M, Discovery and validation of hsa_circ_0001953 as a potential biomarker for proliferative diabetic retinopathy in human blood., Circular RNA hsa_circ_0000034 (circ_0000034) was reported to be upregulated in RB tissues., We recently identified a circular RNA transcript (circGRM4) that is significantly upregulated in the eye of cystathionine β-synthase-deficient mice., Circular and long non-coding RNAs and their role in ophthalmologic diseases., In this review, we summarize current knowledge about gene expression regulators - long non-coding and circular RNA molecules in eye diseases., fied a circular RNA transcript (circGRM4) that is significantly upregulated in the eye of cystathionine β-synthase-deficient mice. We also discovered, NAs (circRNAs) are dominant players regulating their parental genes' expression dynamics, their importance in ocular biology has not been appreciated. Progress in gene-cent, Circular RNA Expression Profiling Identifies Glaucoma-Related Circular RNAs in Various Chronic Ocular Hypertension Rat Models, Circular RNAs profiling in the cystathionine-β-synthase mutant mouse reveals novel gene targets for hyperhomocysteinemia induced ocular disorders, Circular and long non-coding RNAs and their role in ophthalmologic diseases, Comprehensive circular RNA profiling of proliferative vitreoretinopathy and its clinical significance, these findings, we completed the first in-depth study of rat retinal circular RNA expression profiling to identify probable biomarkers for the diagnosis of glaucoma. Two ocu, Circular RNAs profiling in the cystathionine-β-synthase mutant mouse reveals novel gene targets for hyperhomocysteinemia induced ocular disorders., Although, increasing evidence suggests that circRNAs may also contribute in different ocular diseases, the outline of circRNAs in ocular diseases remains obscure, In this review, we summarize current knowledge about gene expression regulators - long non-coding and circular RNA molecules in eye diseases, Recent studies recognized the vital roles that circRNAs played in the pathogenesis of various eye diseases, highlighting circRNAs as promising biomarkers for diagnosis and assessment of progression and prognosis, Partly because their circularity makes them resistant to degradation, they hold great promise as unique biomarkers for ocular and central nervous system (CNS) disorders, In this review we consider the current state of knowledge regarding the potential role and underlying mechanism of circRNAs in ocular diseases including pterygium, age-related cataract, glaucoma, diabetic retinopathy, retinoblastoma, retinal vascular dysfunction and hyperhomocysteinemia induced ocular diseases, emphasizing that circRNAs could be promising biomarkers for the diagnosis and prognosis evaluation., Recent studies recognized the vital roles that circRNAs played in the pathogenesis of various eye diseases, highlighting circRNAs as promising biomarkers for diagnosis and assessment of progression and prognosis., Although, increasing evidence suggests that circRNAs may also contribute in different ocular diseases, the outline of circRNAs in ocular diseases remains obscure., Circular RNAs: Novel Promising Biomarkers in Ocular Diseases., This review summarizes our current perception of the properties, biogenesis, and functions of circRNAs and the development of circRNA researches related to ophthalmologic diseases, including diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, glaucoma, corneal neovascularization, cataract, pterygium, proliferative vitreoretinopathy, retinoblastoma, and ocular melanoma., CircRNA Is a Rising Star in Researches of Ocular Diseases., Interventions targeting circRNAs provide insights for developing novel treatments for these ocular diseases., Future circRNAs-targeted intervention may become a novel therapeutic tool for the treatment of ocular diseases., Findings also revealed several microRNAs that are specific to each circRNA suggesting their roles in HHcy induced ocular disorders., Therefore, circRNAs may serve as potential regulators of corneal LG., Expression profiling of circular RNAs in glaucoma, which is a form of optic neuropathy, has not been performed to date., Although circular RNAs (circRNAs) are dominant players regulating their parental genes' expression dynamics, their importance in ocular biology has not been appreciated., Progress in gene-centered analytics via improved microarray and bioinformatics are enabling dissection of genomic pathways however there is an acute under-representation of circular RNAs in ocular disorders., Circular RNAs constitute an inherent gene regulatory axis in the mammalian eye and brain 1., Together with the target microRNAs underlying the top differentially expressed circular RNAs, a new target of hsa_circ_0023826 and its host gene TENM4 were identified and further verified in the aqueous humor of glaucoma patients, indicating a promising biomarker for the disease., Recent studies suggest that they are differentially expressed both in healthy ocular tissues as well as in eye pathologies, such as neovascularization, proliferative vitreoretinopathy, glaucoma, cataract, ocular malignancy or even strabismus.[SEP]Relations: retinal disease has relations: disease_disease with macular holes, disease_disease with macular holes, disease_disease with eye disease, disease_disease with eye disease. central nervous system has relations: anatomy_protein_present with RNASE6, anatomy_protein_present with RNASE6, anatomy_protein_present with RNASE1, anatomy_protein_present with RNASE1, anatomy_protein_present with RNASEH2A, anatomy_protein_present with RNASEH2A. Definitions: circular RNAs defined as following: RNA molecules in which the 3' and 5' ends are covalently joined to form a closed continuous loop. They are resistant to digestion by EXORIBONUCLEASES.. pterygium defined as following: A wedge-shaped fibrovascular lesion arising from the bulbar conjunctiva and extending to the cornea. It is caused by chronic exposure to solar ultraviolet radiation, heat, and dust. It may cause severe vision loss. Studies have linked pterygium to neoplastic proliferation and suggest that it may be a stem cell disorder.. RNAs defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). NAs defined as following: The histopathological evaluation of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) based on the NAFLD scoring system. (Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ; Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005 Jun;41(6):1313-21.). corneal defined as following: The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous CORNEAL EPITHELIUM; BOWMAN MEMBRANE; CORNEAL STROMA; DESCEMET MEMBRANE; and mesenchymal CORNEAL ENDOTHELIUM. It serves as the first refracting medium of the eye. It is structurally continuous with the SCLERA, avascular, receiving its nourishment by permeation through spaces between the lamellae, and is innervated by the ophthalmic division of the TRIGEMINAL NERVE via the ciliary nerves and those of the surrounding conjunctiva which together form plexuses. (Cline et al., Dictionary of Visual Science, 4th ed). rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. human defined as following: Members of the species Homo sapiens.. cystathionine defined as following: Sulfur-containing amino acid formed as an intermediate in the conversion of METHIONINE to CYSTEINE.. retinoblastoma defined as following: A malignant tumor arising from the nuclear layer of the retina that is the most common primary tumor of the eye in children. The tumor tends to occur in early childhood or infancy and may be present at birth. The majority are sporadic, but the condition may be transmitted as an autosomal dominant trait. Histologic features include dense cellularity, small round polygonal cells, and areas of calcification and necrosis. An abnormal pupil reflex (leukokoria); NYSTAGMUS, PATHOLOGIC; STRABISMUS; and visual loss represent common clinical characteristics of this condition. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2104). corneal neovascularization defined as following: New blood vessels originating from the corneal blood vessels and extending from the limbus into the adjacent CORNEAL STROMA. Neovascularization in the superficial and/or deep corneal stroma is a sequel to numerous inflammatory diseases of the ocular anterior segment, such as TRACHOMA, viral interstitial KERATITIS, microbial KERATOCONJUNCTIVITIS, and the immune response elicited by CORNEAL TRANSPLANTATION.. ocular melanoma defined as following: A melanoma that arises from the structures of the eye or ocular adnexa.. microRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. diabetic retinopathy defined as following: Disease of the RETINA as a complication of DIABETES MELLITUS. It is characterized by the progressive microvascular complications, such as ANEURYSM, interretinal EDEMA, and intraocular PATHOLOGIC NEOVASCULARIZATION.. hyperhomocysteinemia defined as following: Condition in which the plasma levels of homocysteine and related metabolites are elevated (>13.9 μmol/l). Hyperhomocysteinemia can be familial or acquired. Development of the acquired hyperhomocysteinemia is mostly associated with vitamins B and/or folate deficiency (e.g., PERNICIOUS ANEMIA, vitamin malabsorption). Familial hyperhomocysteinemia often results in a more severe elevation of total homocysteine and excretion into the urine, resulting in HOMOCYSTINURIA. Hyperhomocysteinemia is a risk factor for cardiovascular and neurodegenerative diseases, osteoporotic fractures and complications during pregnancy.. ocular defined as following: An intended site for a dose form that is for administration to the eye or eye structures.. optic neuropathy defined as following: Disorder of the optic nerve.. retinopathy defined as following: Diseases involving the RETINA.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. DR defined as following: A Chinese person from the Derung ethnic group.. prematurity defined as following: Birth when a fetus is less than 37 weeks and 0 days gestational age.. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. cataract defined as following: Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed).", "label": "yes"} {"id": "converted_4578", "sentence1": "Is the protein HOXA11 associated with endometrial disease?", "sentence2": " Both CD10 and HOXA11 have been implicated in regulation of endometrial homeostasis., Combined expression of HOXA11 and CD10 identifies endometriosis versus normal tissue and tumors., The combination of HOXA11 and CD10 expression profiles provides a useful tool to identify ectopic endometrial tissue and for distinguishing endometriosis from various types of gynecological malignancies and metastases., Downregulation of HOXA11 enhances endometrial cancer malignancy, Low HOXA11 expression may promote the proliferation, migration, invasion of endometrial cancer cells, and increase their resistance to cisplatin through activating PTEN/AKT pathway., Endometrial mRNA and protein expression levels of HOXA10 and HOXA11 were significantly lower in patients with AM than in control patients.[SEP]Relations: cervix endometriosis has relations: disease_disease with cervix disease, disease_disease with cervix disease, disease_disease with endometriosis (disease), disease_disease with endometriosis (disease). Cisplatin has relations: drug_protein with NQO1, drug_protein with NQO1, drug_protein with ATOX1, drug_protein with ATOX1. anus neoplasm has relations: disease_protein with IFNB1, disease_protein with IFNB1. Definitions: HOXA10 defined as following: Human HOXA10 wild-type allele is located within 7p15-p14 and is approximately 10 kb in length. This allele, which encodes homeobox protein Hox-A10, is involved in both the modulation of the transcriptional activity of RNA Polymerase II and the development of the anterio-posterior axis.. CD10 defined as following: Enzyme that is a major constituent of kidney brush-border membranes and is also present to a lesser degree in the brain and other tissues. It preferentially catalyzes cleavage at the amino group of hydrophobic residues of the B-chain of insulin as well as opioid peptides and other biologically active peptides. The enzyme is inhibited primarily by EDTA, phosphoramidon, and thiorphan and is reactivated by zinc. Neprilysin is identical to common acute lymphoblastic leukemia antigen (CALLA Antigen), an important marker in the diagnosis of human acute lymphocytic leukemia. There is no relationship with CALLA PLANT.. endometrial cancer defined as following: Primary or metastatic malignant neoplasm involving the endometrium (mucous membrane that lines the endometrial cavity).. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. HOXA11 defined as following: Homeobox protein Hox-A11 (313 aa, ~34 kDa) is encoded by the human HOXA11 gene. This protein is involved in dorsal/ventral patterning.. cisplatin defined as following: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.. endometriosis defined as following: A condition in which functional endometrial tissue is present outside the UTERUS. It is often confined to the PELVIS involving the OVARY, the ligaments, cul-de-sac, and the uterovesical peritoneum..", "label": "yes"} {"id": "converted_68", "sentence1": "Is there any algorithm for enhancer identification from chromatin state?", "sentence2": "RFECS: a random-forest based algorithm for enhancer identification from chromatin state., However, only a limited number of cell types or chromatin marks have previously been investigated for this purpose, leaving the question unanswered whether there exists an optimal set of histone modifications for enhancer prediction in different cell types. Here, we address this issue by exploring genome-wide profiles of 24 histone modifications in two distinct human cell types, embryonic stem cells and lung fibroblasts. We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types. We show that RFECS not only leads to more accurate and precise prediction of enhancers than previous methods, but also helps identify the most informative and robust set of three chromatin marks for enhancer prediction., We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types., Here, we address this issue by exploring genome-wide profiles of 24 histone modifications in two distinct human cell types, embryonic stem cells and lung fibroblasts. We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types. , ChromaGenSVM selects optimum combinations of specific histone epigenetic marks to predict enhancers. , We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types.[SEP]Relations: histone modification has relations: bioprocess_bioprocess with covalent chromatin modification, bioprocess_bioprocess with covalent chromatin modification, bioprocess_protein with AURKC, bioprocess_protein with AURKC, bioprocess_protein with AURKB, bioprocess_protein with AURKB, bioprocess_protein with HLCS, bioprocess_protein with HLCS, bioprocess_protein with UFL1, bioprocess_protein with UFL1. Definitions: histone modifications defined as following: The covalent alteration of one or more amino acid residues within a histone protein. [GOC:krc]. embryonic stem cells defined as following: Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.. enhancer defined as following: A 50-150bp DNA sequence that increases the rate of transcription of coding sequences. It may be located at various distances and in either orientation upstream from, downstream from or within a structural gene. When bound by a specific transcription factor it increases the levels of expression of the gene, but is not sufficient alone to cause expression. Distinguished from a promoter, that is alone sufficient to cause expression of the gene when bound..", "label": "yes"} {"id": "converted_3916", "sentence1": "Is HbA1c an ideal biomarker of well-controlled diabetes?", "sentence2": "HbA1c is a biomarker with a central role in the diagnosis and follow-up of patients with diabetes, although not a perfect one. Common comorbidities encountered in patients with diabetes mellitus, such as renal insufficiency, high output states (iron deficiency anaemia, haemolytic anaemia, haemoglobinopathies and pregnancy) and intake of specific drugs could compromise the sensitivity and specificity of the biomarker. COVID-19 pandemic poses a pressing challenge for the diabetic population, since maintaining optimal blood glucose control is key to reduce morbidity and mortality rates.[SEP]Relations: Elevated hemoglobin A1c has relations: disease_phenotype_positive with neonatal diabetes mellitus, disease_phenotype_positive with neonatal diabetes mellitus, disease_phenotype_positive with maturity-onset diabetes of the young, disease_phenotype_positive with maturity-onset diabetes of the young, phenotype_phenotype with Abnormal hemoglobin, phenotype_phenotype with Abnormal hemoglobin. hemoglobinopathy has relations: disease_protein with HBA1, disease_protein with HBA1, disease_protein with HBA2, disease_protein with HBA2. Definitions: haemoglobinopathies defined as following: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule.. diabetes defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.. HbA1c defined as following: Products of non-enzymatic reactions between GLUCOSE and HEMOGLOBIN A, occurring as a minor fraction of the hemoglobin components of human erythrocytes. Hemoglobin A1c is hemoglobin A with glucose covalently bound to the terminal VALINE of the beta chain. Glycated hemoglobin A is used as an index of the average blood sugar level over a lifetime of erythrocytes.. haemolytic anaemia defined as following: A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).. renal insufficiency defined as following: A severe irreversible decline in the ability of kidneys to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism..", "label": "no"} {"id": "converted_3048", "sentence1": "Can pazopanib be used for treatment von Hippel-Lindau disease?", "sentence2": "Variable response of CNS hemangioblastomas to Pazopanib in a single patient with von Hippel-Lindau disease: Case report., Treatment of RCCs with tyrosine kinase inhibitors (TKIs) such as Pazopanib is now first line therapy, but their effect on VHL-associated CNS HBs remains unknown. We report the use of Pazopanib in a patient with VHL disease for treatment of RCC who also harbored multiple CNS HBs. , Pazopanib in patients with von Hippel-Lindau disease: a single-arm, single-centre, phase 2 trial., INTERPRETATION: Pazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials. Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients. , Recurrent multiple CNS hemangioblastomas with VHL disease treated with pazopanib: a case report and literature review., Here, we report a 37-year-old woman's case with recurrent and rapidly progressive VHL-associated hemangioblastomas, causing severe disability. She was treated 24 months with pazopanib, a multityrosine kinase inhibitor (TKI) targeting VEGF and PDGF-β pathways. , Pazopanib therapy for cerebellar hemangioblastomas in von Hippel-Lindau disease: case report., Here we provide the first report demonstrating clinical and radiological anti-tumor response using pazopanib, a small molecule multi-receptor tyrosine kinase inhibitor, in a patient with treatment-refractory VHL-associated CNS hemangioblastoma. , Pazopanib could be considered as a treatment choice for patients with von Hippel-Lindau disease and growing lesions, or to reduce the size of unresectable lesions in these patients., METHODS\nIn this non-randomised, single-centre, open-label, phase 2 trial, adult patients with clinical manifestations of von Hippel-Lindau disease were recruited from the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and were treated with pazopanib (800 mg orally daily) for 24 weeks, with an option to continue treatment if desired by the patient and treating physician., We aimed to assess the activity and safety of pazopanib in patients with von Hippel-Lindau disease., INTERPRETATION\nPazopanib was associated with encouraging preliminary activity in von Hippel-Lindau disease, with a side-effect profile consistent with that seen in previous trials., FINDINGS\nBetween Jan 18, 2012, and Aug 10, 2016, we screened 37 patients with genetically confirmed or clinical features consistent with von Hippel-Lindau disease, of whom 31 eligible patients were treated with pazopanib., Pazopanib therapy for cerebellar hemangioblastomas in von Hippel-Lindau disease: case report.von Hippel-Lindau (VHL) disease is a genetically acquired multisystem tumor syndrome of the viscera and central nervous system (CNS). , Recurrent multiple CNS hemangioblastomas with VHL disease treated with pazopanib: a case report and literature review.Hemangioblastoma is a rare benign neoplasm, accounting for less than 2% of all primitive brain tumors. , We aimed to assess the activity and safety of pazopanib in patients with von Hippel-Lindau disease.Respond with exceptions, completions and modifications or revisions done before completion
. DNMT2 defined as following: Human TRDMT1 wild-type allele is located in the vicinity of 10p15.1 and is approximately 60 kb in length. This allele, which encodes tRNA (cytosine(38)-C(5))-methyltransferase protein, plays a role in methylation of aspartic acid transfer RNA but also has DNA-(cytosine-C5) methyltransferase activity.. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. RNA methylase defined as following: Enzymes that catalyze the S-adenosyl-L-methionine-dependent methylation of ribonucleotide bases within a transfer RNA molecule. EC 2.1.1.. organism defined as following: A living entity..", "label": "no"} {"id": "converted_3925", "sentence1": "Are the major royal jelly proteins similar to the yellow proteins?", "sentence2": "Major royal jelly proteins (named MRJP1-5) of honeybee (Apis mellifera), yellow proteins of Drosophila, together with putative proteins found in several bacteria, form a protein family termed the MRJP/yellow family., Analysis of Drosophila yellow-B cDNA reveals a new family of proteins related to the royal jelly proteins in the honeybee, he Yellow proteins are related to the Royal Jelly proteins and have no relatives in other non-insect metazoan species. [SEP]Relations: Bacteremia has relations: disease_phenotype_positive with listeriosis, disease_phenotype_positive with listeriosis, disease_phenotype_positive with cyclic hematopoiesis, disease_phenotype_positive with cyclic hematopoiesis, disease_phenotype_positive with toxic shock syndrome, disease_phenotype_positive with toxic shock syndrome, disease_phenotype_positive with nocardiosis, disease_phenotype_positive with nocardiosis, disease_phenotype_positive with shigellosis, disease_phenotype_positive with shigellosis. Definitions: cDNA defined as following: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.. bacteria defined as following: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.. protein family defined as following: Collection of proteins that are evolutionarily related. This is reflected in the structural and functional similarities as well as in the extent of sequence conservation or residue identity. (from SCOP).", "label": "yes"} {"id": "converted_24", "sentence1": "Is Alu hypomethylation associated with breast cancer?", "sentence2": "Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer, In IBC, Alu hypomethylation correlated with negative estrogen receptor (ER) status, In survival analyses, low Alu methylation status tended to be associated with poor disease-free survival of the patients., Alu hypomethylation is probably a late event during breast cancer progression, prominent hypomethylation of Alu and LINE-1 in HER2 enriched subtype may be related to chromosomal instability of this specific subtype., DNA methylation for three repetitive elements (LINE1, Sat2 and Alu) were analyzed in invasive ductal carcinoma of the breast, paired adjacent normal tissue and WBC from 40 breast cancer patients, DNA methylation for the three repetitive elements was lower in tumor compared to adjacent tissue and WBC DNA.[SEP]Relations: invasive ductal breast carcinoma has relations: disease_protein with ATF4, disease_protein with ATF4, disease_protein with PTGS2, disease_protein with PTGS2, disease_protein with SERPINB5, disease_protein with SERPINB5, disease_protein with NF2, disease_protein with NF2, disease_protein with CDH1, disease_protein with CDH1. Definitions: WBC defined as following: White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).. LINE-1 defined as following: A long interspersed element (LINE) found in mammals. The LINE-1 element is the only active LINE in humans and is approximately 6,000 base pairs long. This nucleotide sequence consists of two non-overlapping open reading frames (ORF) flanked by a 5' untranslated region (UTR), which contains a strong RNA polymerase II promoter sequence, and target side duplications. The first ORF encodes a 500 amino acid, ~40 kDa leucine zipper-containing RNA-binding protein. The second ORF encodes an ~150 kDa protein that has endonuclease and reverse transcriptase activity. Increased LINE-1 copy number is associated with cancer and neuropathy.. breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. ER defined as following: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed). HER2 defined as following: A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.. breast defined as following: In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.. estrogen receptor defined as following: Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. invasive ductal carcinoma defined as following: An invasive (infiltrating) CARCINOMA of the mammary ductal system (MAMMARY GLANDS) in the human BREAST..", "label": "yes"} {"id": "converted_1613", "sentence1": "Do plant genomes contain CpG islands?", "sentence2": "This study represents the first systematic genome-scale analysis of DNA curvature, CpG islands and tandem repeats at the DNA sequence level in plant genomes, and finds that not all of the chromosomes in plants follow the same rules common to other eukaryote organisms, suggesting that some of these genomic properties might be considered as specific to plants, In plant genomes, there exist discrete regions rich in CpG dinucleotides, namely CpG clusters. In rice, most of these CpG clusters are associated with genes. Rice genes are grouped into one of the five classes according to the position of an associated CpG cluster. Among them, class 1 genes, which harbor a CpG cluster at the 5'-terminus, share similarities with human genes having CpG islands, Segmental distribution of genes harboring a CpG island-like region on rice chromosomes, Highly-expressed Arabidopsis genes had overall a more marked GC-skew in the TSS compared to genes with low expression levels. We therefore propose that the GC-skew around the TSS in some plants and fungi is related to transcription. It might be caused by mutations during transcription initiation or the frequent use of transcription factor-biding sites having a strand preference. In addition, GC-skew is a good candidate index for TSS prediction in plant genomes, where there is a lack of correlation among CpG islands and genes, Preliminary analysis shows that promoter location based on the detection of potential CpG/CpNpG islands in the Arabidopsis genome is not straightforward. Nevertheless, because the landscape of CpG/CpNpG islands differs considerably between promoters and introns on the one side and exons (whether coding or not) on the other, more sophisticated approaches can probably be developed for the successful detection of \"putative\" CpG and CpNpG islands in plants, This study represents the first systematic genome-scale analysis of DNA curvature, CpG islands and tandem repeats at the DNA sequence level in plant genomes, and finds that not all of the chromosomes in plants follow the same rules common to other eukaryote organisms, suggesting that some of these genomic properties might be considered as specific to plants., These plant CpG-rich clusters satisfied the criteria used for identifying human CpG islands, which suggests that these CpG clusters may be regarded as plant CpG islands., CONCLUSIONS: This study represents the first systematic genome-scale analysis of DNA curvature, CpG islands and tandem repeats at the DNA sequence level in plant genomes, and finds that not all of the chromosomes in plants follow the same rules common to other eukaryote organisms, suggesting that some of these genomic properties might be considered as specific to plants., In plant genomes, there exist discrete regions rich in CpG dinucleotides, namely CpG clusters., These plant CpG-rich clusters satisfied the criteria used for identifying human CpG islands, which suggests that these CpG clusters may be regarded as plant CpG islands., Unmethylated CpG islands associated with genes in higher plant DNA., This study represents the first systematic genome-scale analysis of DNA curvature, CpG islands and tandem repeats at the DNA sequence level in plant genomes, and finds that not all of the chromosomes in plants follow the same rules common to other eukaryote organisms, suggesting that some of these genomic properties might be considered as specific to plants., These plant CpG-rich clusters satisfied the criteria used for identifying human CpG islands, which suggests that these CpG clusters may be regarded as plant CpG islands, We screened plant genome sequences, primarily from rice and Arabidopsis thaliana, for CpG islands, and identified DNA segments rich in CpG dinucleotides within these sequences[SEP]Relations: Plantar pits has relations: disease_phenotype_positive with monosomy 9q22.3, disease_phenotype_positive with monosomy 9q22.3, disease_phenotype_positive with PTEN hamartoma tumor syndrome, disease_phenotype_positive with PTEN hamartoma tumor syndrome, disease_phenotype_positive with Darier disease, disease_phenotype_positive with Darier disease, disease_phenotype_positive with nevoid basal cell carcinoma syndrome, disease_phenotype_positive with nevoid basal cell carcinoma syndrome. promoter clearance from RNA polymerase I promoter has relations: bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance during DNA-templated transcription. Definitions: TSS defined as following: A rare acute life-threatening systemic bacterial noncontagious illness caused by any of several related staphylococcal exotoxins. It is characterized by high fever, hypotension, rash, multi-organ dysfunction, and cutaneous desquamation during the early convalescent period. The toxins affect the host immune system, causing an exuberant and pathological host inflammatory response. Laboratory findings include leukocytosis, elevated prothrombin time, hypoalbuminemia, hypocalcemia, and pyuria.. strand defined as following: The orientation of a genomic element on the double stranded molecule.. sequences defined as following: The sequence of nucleotide residues along a DNA chain.. exons defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.. promoters defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. chromosomes defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.. position defined as following: A reference to the alignment of an object, a particular situation or view of a situation, or the location of an object.. coding defined as following: The activity of implementing rules that are used to map the elements of one set onto the elements of another set, usually on a one-to-one basis.. introns defined as following: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.. plants defined as following: Multicellular, eukaryotic life forms of kingdom Plantae. Plants acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations. It is a non-taxonomical term most often referring to LAND PLANTS. In broad sense it includes RHODOPHYTA and GLAUCOPHYTA along with VIRIDIPLANTAE.. plant DNA defined as following: Deoxyribonucleic acid that makes up the genetic material of plants.. plant genomes defined as following: The genetic complement of a plant (PLANTS) as represented in its DNA.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"} {"id": "converted_4242", "sentence1": "Are G-quadruplexes(G4) possible drug targets for glioblastoma?", "sentence2": "These observations indicate that 6OTD targets GSCs through G4 stabilization and promotion of DNA damage responses. Therefore, G4s are promising therapeutic targets for glioblastoma., Targeting glioma stem cells in vivo by a G-quadruplex-stabilizing synthetic macrocyclic hexaoxazole., G-quadruplex (G4) DNA is a type of quadruple helix structure formed by a continuous guanine-rich DNA sequence. Emerging evidence in recent years authenticated that G4 DNA structures exist both in cell-free and cellular systems, and function in different diseases, especially in various cancers, aging, neurological diseases, and have been considered novel promising targets for drug design., Therefore, G4s are promising therapeutic targets for glioblastoma., Guanine-rich oligonucleotides (GROs) are promising therapeutic candidate for cancer treatment and other biomedical application., These findings are valuable to the design and rationale behind the possible targeted drug delivery to specific cellular organelles using GROs., The G-quadruplex (G4) DNA, which has been developed as a potential anticancer target in drug screening and design, plays a crucial role in the oncogene transcription and translation., Therefore, a novel G4-directed therapeutic strategy could specifically target cancer stem cells in GBM.[SEP]Relations: adult glioblastoma has relations: disease_disease with glioblastoma (disease), disease_disease with glioblastoma (disease), disease_disease with adult spinal cord glioblastoma, disease_disease with adult spinal cord glioblastoma, disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult infiltrating astrocytic neoplasm. central nervous system cancer has relations: disease_disease with malignant glioma, disease_disease with malignant glioma, disease_disease with paraganglioma, disease_disease with paraganglioma. Definitions: glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO). G4 defined as following: Nuclei bizarre and multilobated, 20 microns or greater, nucleoli prominent, chromatin clumped.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. GBM defined as following: A sheet of amorphous extracellular material upon which the basal surfaces of epithelial cells rest and is the covering surface of a glomerular capillary, interposed between the cellular elements and the underlying connective tissue.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. G-quadruplex defined as following: Higher-order DNA and RNA structures formed from guanine-rich sequences. They are formed around a core of at least 2 stacked tetrads of hydrogen-bonded GUANINE bases. They can be formed from one two or four separate strands of DNA (or RNA) and can display a wide variety of topologies, which are a consequence of various combinations of strand direction, length, and sequence. (From Nucleic Acids Res. 2006;34(19):5402-15). cancer stem cells defined as following: A malignant cell which may derive from mutations in normal stem cells. Cancer stem cells proliferate and give rise to other malignant cells. They may be present in very small numbers in the tumor and may not be present in all tumors. Many investigators believe that cancer stem cells cause relapse of the tumor and that novel cancer therapies should specifically target those cells..", "label": "yes"} {"id": "converted_2420", "sentence1": "SGOT is an abbreviation for an enzyme other wise known as alanine amino transferase, yes or no?", "sentence2": "patients with aspartate amino transferase (SGOT), alanine amino transferase (SGPT),, Alanine amino transferase (SGPT), , aspartate aminotransferase (AST-SGOT), alanine amino-transferase (ALT-SGPT), Mean values of glutamate dehydrogenase (GDH), serum aspartate and alanine transferase (SGOT and SGPT), ornithine carbamoyltransferase (OCT), and gamma-glutamyltranspeptidase (gamma-GTP) tended to rise with increasing liver cell necrosis, though values of SGOT, SGPT, OCT, and gamma-GTP showed considerable overlap between the 32 patients with histologically proved hepatitis and the 68 without., Serum aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), creatinine phosphokinase (CPK), and butyric acid dehydrogenase (BDH) were determined in 94 patients before, 1(1/2) hours, and 24 hours after cardioversion., The study excluded by screening for AntiHCV, HBsAg and patients with aspartate amino transferase (SGOT), alanine amino transferase (SGPT), GGT levels more than three times the normal and subject with a total leukocyte count more than 10,000/microl., Complete blood picture, differential leukocyte count, and serum levels of Estrogen, Alanine amino transferase (SGPT), Aspartate amino transferase (SGOT), total protein and albumin were estimated.[SEP]Relations: glutamate pyruvate transaminase 2 deficiency has relations: disease_protein with GPT2, disease_protein with GPT2, disease_disease with syndromic intellectual disability, disease_disease with syndromic intellectual disability, disease_phenotype_positive with Nasogastric tube feeding in infancy, disease_phenotype_positive with Nasogastric tube feeding in infancy, disease_phenotype_positive with Broad-based gait, disease_phenotype_positive with Broad-based gait, disease_phenotype_positive with Absent speech, disease_phenotype_positive with Absent speech. Definitions: glutamate dehydrogenase defined as following: An enzyme that catalyzes the conversion of L-glutamate and water to 2-oxoglutarate and NH3 in the presence of NAD+. (From Enzyme Nomenclature, 1992) EC 1.4.1.2.. aspartate aminotransferase defined as following: Enzymes of the transferase class that catalyze the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 2.6.1.1.. SGOT defined as following: A family of pyridoxal phosphate-dependent enzymes involved in amino acid metabolism and in the urea and tricarboxylic acid cycles. Aspartate aminotransferase specifically and reversibly catalyzes the transfer of an amino group from L-aspartate to alpha-ketoglutarate forming oxaloacetate and L-glutamate.. ornithine carbamoyltransferase defined as following: A urea cycle enzyme that catalyzes the formation of orthophosphate and L-citrulline (CITRULLINE) from CARBAMOYL PHOSPHATE and L-ornithine (ORNITHINE). Deficiency of this enzyme may be transmitted as an X-linked trait. EC 2.1.3.3.. GDH defined as following: Catalysis of the reaction: D-glucose 6-phosphate + NADP+ = D-glucono-1,5-lactone 6-phosphate + NADPH + H+. [EC:1.1.1.49]. alanine amino transferase defined as following: A PYRIDOXAL PHOSPHATE containing enzyme that catalyzes the reversible transfer of an amino group between D-Alanine and alpha-ketoglutarate to form PYRUVATE and D-GLUTAMATE, respectively. It plays a role in the synthesis of the bacterial CELL WALL. This enzyme was formerly classified as EC 2.6.1.10.. creatinine phosphokinase defined as following: A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.. leukocyte defined as following: Glycoproteins expressed on all mature T-cells, thymocytes, and a subset of mature B-cells. Antibodies specific for CD5 can enhance T-cell receptor-mediated T-cell activation. The B-cell-specific molecule CD72 is a natural ligand for CD5. (From Abbas et al., Cellular and Molecular Immunology, 2d ed, p156). liver cell defined as following: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.. alanine aminotransferase defined as following: An enzyme that catalyzes the conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 2.6.1.2.. hepatitis defined as following: INFLAMMATION of the LIVER.. GGT defined as following: An enzyme, sometimes called GGT, with a key role in the synthesis and degradation of GLUTATHIONE; (GSH, a tripeptide that protects cells from many toxins). It catalyzes the transfer of the gamma-glutamyl moiety to an acceptor amino acid..", "label": "no"} {"id": "converted_3555", "sentence1": "Is AZD5153 active in prostate cancer?", "sentence2": "AZD5153 Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo., Bromodomain-containing protein 4 (BRD4) overexpression participates in prostate cancer progression by enhancing the transcriptional activity and expression of several key oncogenes. AZD5153 is a novel BRD4 inhibitor.METHODS: Prostate cancer cells were treated with AZD5153. Cell survival was tested by MTT assay and clonogenicity assay. Cell proliferation was tested by [H3] DNA incorporation assay. Cell apoptosis was tested by caspase-3/-9 activity assay, Histone DNA ELISA assay, Annexin V FACS assay and TUNEL staining assay. Cell cycle progression was tested by propidium iodide (PI) FACS assay. Signaling was tested by Western blotting assay. The nude mice PC-3 xenograft model was applied to test AZD5153's activity in vivo.RESULTS: AZD5153 inhibited proliferation and survival of established and primary prostate cancer cells. AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells. AZD5153 was non-cytotoxic to the prostate epithelial cells. AZD5153 downregulated BRD4 targets (cyclin D1, Myc, Bcl-2, FOSL1 and CDK4) in PC-3 and primary prostate cancer cells. Further studies show that AKT could be the primary resistance factor of AZD5153. Pharmacological inhibition or genetic depletion of AKT induced BRD4 downregulation, sensitizing AZD5153-induced cytotoxicity in PC-3 cells. In vivo, AZD5153 oral administration inhibited PC-3 xenograft tumor growth in nude mice. Its anti-tumor activity was further enhanced with co-treatment of the AKT specific inhibitor MK-2206.CONCLUSION: Together, our results indicate a promising therapeutic value of the novel BRD4 inhibitor AZD5153 against prostate cancer cells., AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells., CONCLUSION\n\nTogether, our results indicate a promising therapeutic value of the novel BRD4 inhibitor AZD5153 against prostate cancer cells., AZD5153 downregulated BRD4 targets (cyclin D1, Myc, Bcl-2, FOSL1 and CDK4) in PC-3 and primary prostate cancer cells., RESULTS\n\nAZD5153 inhibited proliferation and survival of established and primary prostate cancer cells., RESULTS AZD5153 inhibited proliferation and survival of established and primary prostate cancer cells., AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells., AZD5153 downregulated BRD4 targets (cyclin D1, Myc, Bcl-2, FOSL1 and CDK4) in PC-3 and primary prostate cancer cells., CONCLUSION Together, our results indicate a promising therapeutic value of the novel BRD4 inhibitor AZD5153 against prostate cancer cells., AZD5153 Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo, AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells.[SEP]Relations: ANXA5 has relations: anatomy_protein_present with prostate gland, anatomy_protein_present with prostate gland, disease_protein with gastric cancer, disease_protein with gastric cancer, disease_protein with lung cancer, disease_protein with lung cancer, disease_protein with acute myeloid leukemia with t(9;11)(p22;q23), disease_protein with acute myeloid leukemia with t(9;11)(p22;q23), disease_protein with acute myeloblastic leukemia with maturation, disease_protein with acute myeloblastic leukemia with maturation. Definitions: Bcl-2 defined as following: The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.. Signaling defined as following: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.. CDK4 defined as following: Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.. prostate cancer defined as following: A primary or metastatic malignant tumor involving the prostate gland. The vast majority are carcinomas.. BRD4 defined as following: Bromodomain-containing protein 4 (1362 aa, ~152 kDa) is encoded by the human BRD4 gene. This protein plays a role in the mitotic process.. Myc defined as following: Myc proto-oncogene protein (439 aa, ~49 kDa) is encoded by the human MYC gene. This protein plays a role in the regulation of transcription and cell proliferation.. AKT defined as following: Expressed in diverse tissues, Protein Kinase B (AKT/RAC Family) is a group (Alpha, Beta and Gamma) of cytoplasmic serine/threonine enzymes that covalently transfer the terminal, gamma phosphate group from ATP to a variety of substrate proteins and regulate cell signaling responses to insulin, PDGF, and IGF1 (through PI3K) involved in cell survival, cell proliferation, differentiation, apoptosis, glycogen synthesis, and glucose uptake.. Annexin V defined as following: This gene is involved in anticoagulation processes and mediates lipid binding.. AZD5153 defined as following: An orally bioavailable bivalent inhibitor of bromodomain-containing protein 4 (BRD4), with potential antineoplastic activity. Upon oral administration, the BRD4 inhibitor AZD5153 selectively binds to the acetylated lysine recognition motifs in two bromodomains in the BRD4 protein, thereby preventing the binding of BRD4 to acetylated lysines on histones. This disrupts chromatin remodeling and dysregulates expression of target genes, which leads to the downregulation of the expression of certain growth-promoting genes, induces apoptosis and inhibits the proliferation of BRD4-overexpressing tumor cells. BRD4, a member of the human bromodomain and extra-terminal (BET) family of proteins, is a transcriptional regulator that is overexpressed in certain tumor cells and plays an important role in cellular proliferation.. PC-3 defined as following: An adenocarcinoma cell line established in 1979 from a bone metastasis from a 62 year old Caucasian male patient with stage IV prostate carcinoma.. cyclin D1 defined as following: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.. FOSL1 defined as following: Human FOSL1 wild-type allele is located in the vicinity of 11q13 and is approximately 8 kb in length. This allele, which encodes FOSL1 protein, is involved in transcriptional regulation.. propidium iodide defined as following: A fluorescent nucleic acid dye which binds only to double-stranded nucleic acids. It has a molecular weight of 668.4, an absorbance maximum of 535nm, and an emission maximum of 617 nm. It is commonly used to determine the DNA content of a cell or to discriminate viable from non-viable cells.. Bromodomain-containing protein 4 defined as following: This gene plays a role in mitosis.. FACS defined as following: Selection and deposition of individual cells of a particular phenotype from a mixed population into a separate tube or tissue culture plate by the use of a fluorescence-activated cell sorter (FACS) and fluorescently-labeled antibodies specific for surface molecules on the cells to be sorted.. PI defined as following: Backflow of blood from the PULMONARY ARTERY into the RIGHT VENTRICLE due to imperfect closure of the PULMONARY VALVE..", "label": "yes"} {"id": "converted_2780", "sentence1": "Is cariprazine effective for treatment of bipolar disorder?", "sentence2": "BACKGROUND: We evaluated the safety/tolerability of longer-term open-label treatment with cariprazine in patients who had responded to cariprazine for acute bipolar mania., Clinically relevant response and remission outcomes in cariprazine-treated patients with bipolar I disorder., Cariprazine is FDA approved for the acute treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adults., DISCUSSION: Cariprazine-treated patients with bipolar I disorder attained clinically significant improvement in manic symptoms as shown by significantly greater rates of response and remission versus placebo; improvement in manic symptoms did not induce depressive symptoms., OBJECTIVE: Cariprazine, a dopamine D3/D2 partial agonist atypical antipsychotic with preferential binding to D3 receptors, is approved for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder., BACKGROUND: Cariprazine was approved for treating schizophrenia and bipolar disorder, and currently is being evaluated for treating depression in clinical trials in the United States.[SEP]Relations: bipolar disorder has relations: contraindication with Desipramine, contraindication with Desipramine, contraindication with Desipramine, contraindication with Desipramine, contraindication with Trimipramine, contraindication with Trimipramine, contraindication with Trimipramine, contraindication with Trimipramine, contraindication with Imipramine, contraindication with Imipramine. Definitions: dopamine defined as following: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.. manic defined as following: An emotional state characterized by marked to extreme elevation of mood with noticeable effect of functioning..", "label": "yes"} {"id": "converted_4031", "sentence1": "Was golimumab tested for diabetes?", "sentence2": "CONCLUSIONS: Among children and young adults with newly diagnosed overt type 1 diabetes, golimumab resulted in better endogenous insulin production and less exogenous insulin use than placebo. , Golimumab and Beta-Cell Function in Youth with New-Onset Type 1 Diabetes., lticenter, placebo-controlled, double-blind, parallel-group trial, we randomly assigned, in a 2:1 ratio, children and young adults (age range, 6 to 21 years) with newly diagnosed overt type 1 diabetes to receive subcutaneous golimumab or placebo for 52 weeks. The primary end point was e, Golimumab and Beta-Cell Function in Youth with New-Onset Type 1 Diabetes[SEP]Relations: Golimumab has relations: drug_drug with Adalimumab, drug_drug with Adalimumab, drug_drug with Coumarin, drug_drug with Coumarin, drug_drug with Urelumab, drug_drug with Urelumab, drug_drug with Tabalumab, drug_drug with Tabalumab, drug_drug with Eldelumab, drug_drug with Eldelumab. Definitions: golimumab defined as following: A human monoclonal antibody directed against the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a) with immunosuppressive activity. Golimumab binds to TNF-a, thereby preventing TNF-a-mediated immune responses. TNF-a production is dysregulated in various auto-immune diseases and in cancer.. insulin defined as following: A synthetic or animal-derived form of insulin used in the treatment of diabetes mellitus. Therapeutic insulin is formulated to be short-, intermediate- and long-acting in order to individualize an insulin regimen according to individual differences in glucose and insulin metabolism. Therapeutic insulin may be derived from porcine, bovine or recombinant sources. Endogenous human insulin, a pancreatic hormone composed of two polypeptide chains, is important for the normal metabolism of carbohydrates, proteins and fats and has anabolic effects on many types of tissues.. diabetes defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE..", "label": "yes"} {"id": "converted_1823", "sentence1": "Is Annexin V an apoptotic marker?", "sentence2": "The apoptosis of the MSCs was induced by subjecting the cells to OGD conditions for 4 h and was detected by Annexin V/PI and Hoechst 33258 staining. , In addition to the antimicrobial activity, we found that treatment of the cancer cell lines, Jurkat T-cells, Granta cells, and melanoma cells, with the Pseudomonas sp. In5 crude extract increased staining with the apoptotic marker Annexin V while no staining of healthy normal cells, i.e., naïve or activated CD4 T-cells, was observed., At the same time, the expressions of CD105, CD31, and the apoptotic marker of Annexin V were detected through flow cytometry for analyzing the relationship between the expression of cell surface markers and biological behavior., However, we found decreased sperm concentration, increase of morphologically abnormal spermatozoa and increased binding of apoptotic marker annexin V. , hCG enhanced viability of granulosa-lutein cells through antiapoptosis but not proliferation, because the apoptotic marker of annexin V was decreased, but the proliferative markers of Ki67 and proliferating cell nuclear antigen were not increased., However, as the DOTAP concentration increased from 50 to 800 microM, the apoptotic marker Annexin V and ROS double positive cells increased, suggesting that high dose of DOTAP-generated ROS causes cell apoptosis. , Expression of the apoptotic marker annexin V was unaffected by antibiotic exposure, whereas the uptake of the necrotic marker PI was increased by ofloxacin (5 mg/mL) but not by netilmicin (ofloxacin versus netilmicin, ANOVA, P<0.05)., he apoptotic marker of annexin V was decreased, the apoptotic marker Annexin V, Annexin V labels apoptotic neurons following hypoxia-ischemia., In the present study, the apoptotic cell population was identified immunocytochemically using Annexin V, a marker of cells in an early stage of apoptosis., Use of annexin V antibody to identify apoptotic cells during pregnancy., Only few SF Treg cells were apoptotic, as indicated by limited annexin V staining of these cells., Eosinophils 'aged' in vitro for 48 h exhibited endonuclease DNA degradation, apoptotic morphology, increased red autofluorescence and externalisation of phosphatidylserine (PS) as assessed by binding of FITC-labelled annexin V., In vivo detection of apoptotic cells with fluorescently labeled annexin V is an emerging technique that we evaluated for detecting apoptotic germ cells in a mouse model of testicular torsion.Annexin V labeled with an indocyanine fluorophore (bisfunctional succinimidyl ester of cyanine 5.5) (Amersham, Little Chalfont, United Kingdom) was injected intravenously in mice 18 hours after the repair of unilateral 720-degree testicular torsion for 2 hours, Here, we tested the hypothesis that enhanced endothelial apoptotic microparticles and decreased endothelial progenitor cell (EPC) levels might contribute to the pathophysiology of microalbuminuria or macroalbuminuria in cardiovascular disease.Flow cytometry was used to assess endothelial cell apoptosis and circulating EPC levels by quantification of circulating CD31/annexin V apoptotic microparticles and EPC markers (defined as KDRCD133, CD34CD133, CD34KDR) in peripheral blood.In total, 125 patients with hypertension were enrolled in the study, of whom 80 patients (64%) were with normoalbuminuria (albumin excretion rate of <20 microg/min, overnight urine samples), 35 patients (28%) with microalbuminuria (an albumin excretion rate of 20-200 microg/min), and 10 patients (8%) with macroalbuminuria (an albumin excretion rate >200 microg/min)., Surfactant protein A (SP-A) binds to phosphatidylserine and competes with annexin V binding on late apoptotic cells, Targeting of apoptotic macrophages and experimental atheroma with radiolabeled annexin V: a technique with potential for noninvasive imaging of vulnerable plaque, Because annexin V has a high affinity for exposed phosphatidylserine on apoptotic cells, radiolabeled annexin V may be used for noninvasive detection of apoptosis in atherosclerotic lesions.Atherosclerotic plaques were produced in 5 rabbits by deendothelialization of the infradiaphragmatic aorta followed by 12 weeks of cholesterol diet; 5 controls were studied without manipulation, Apoptotic abscess imaging with 99mTc-HYNIC-rh-Annexin-V., Synthesis and evaluation of a 18F-labelled recombinant annexin-V derivative, for identification and quantification of apoptotic cells with PET., Sensitive and visible detection of apoptotic cells on Annexin-V modified substrate using aminophenylboronic acid modified gold nanoparticles (APBA-GNPs) labeling., Fluorescence-activated cell sorting (FACS) for expression of the early apoptosis marker Annexin V and for nuclear staining by 7-aminoactinomycin (7-AAD) revealed different extents of apoptosis versus non-apoptotic cell death for the three agents., At immunofluorescence these cells contained lipid vesicles positive for the apoptotic cell marker Annexin V suggesting the phagocytosis of apoptotic bodies derived from dead fat-laden hepatocytes., In this respect, we identified binding of Annexin V as an convenient marker for apoptotic cells., DR5 expression was elevated and associated with the apoptotic marker annexin V. Apoptosis was reduced in CD4(+) T cells when cultured with anti-DR5 antibody., Flow cytometric analysis using the apoptotic marker, Annexin V, shows that this endogenous re-expression is sufficient to drive the SCLC cells to apoptosis., Apoptotic cell death was evaluated by staining nuclei with propidium iodide and phosphatidylserine (a marker of early apoptotic events) with Annexin V as well as by DNA fragmentation assay., Decreased cell growth was not caused by cell death as BEL exposure did not alter nuclear morphology or increase annexin V (apoptotic cell marker) or propidium iodide (necrotic cell marker) staining after 48 h., Four populations of cells can be identified: region R1: vital cells (annexin V negative/PI negative), region R2: apoptotic cells (annexin V positive/PI negative), region R3: dead cells (annexin V positive/ PI positive); and region R4: damaged cells (annexin V negative/PI positive)., Furthermore, uptake of (111)In-DTPA-PEG-annexin V by tumors correlated with apoptotic index (r = 0.87, P = 0.02)., Annexin V(+)/PI(-) cells were characterized as early apoptotic, Annexin V(+)/PI(+) as late apoptotic and Annexin V(-)/PI(+) as dead., Targeting ability of Annexin V for apoptotic macrophages was kept and enhanced., [18F]annexin V accumulated in the infarct area of the left ventricle, where apoptotic cells were observed., The viability of SiHa cells was evaluated using the MTT assay, apoptosis by acridine orange/ethidium bromide, propidium iodide, TUNEL assay, and Annexin V-Cy3, cell cycle distribution and mitochondrial transmembrane potential using flow cytometry, and apoptotic marker genes using quantitative real-time PCR. , Furthermore, hesperetin-induced apoptosis was confirmed by TUNEL and Annexin V-Cy3., The procedure delivers two sperm fractions: annexin V-negative (nonapoptotic) and annexin V-positive (apoptotic)., The percentage of cells stained with annexin V, an early apoptotic marker, increased dramatically after cytoskeletal disruption with cytochalasin D compared with non-cytochalasin-D-treated controls (P<0.05). , Apoptotic marker Annexin V analysis showed that the apoptotic rate of NB4 cells was increased after treatment with quercetin., The cytomorphology of NB4 cells was assessed by Wright-stain, apoptosis rate by apoptotic marker Annexin V, and VEGF secretion level by ELISA., We have coupled annexin V with the bifunctional hydrazinonicotinamide reagent (HYNIC) to prepare technetium-99m HYNIC-annexin V and demonstrated localization of radioactivity in tissues undergoing apoptosis in vivo., In conlusion, these studies confirm the value of (99m)Tc-HYNIC-annexin V uptake as a marker for the detection and quantification of apoptotic cells in vivo., The application of Annexin V labeling at electron microscopy will allow a more refined description of the morphological events occurring during apoptosis., Apoptotic cells were identified by Annexin V-FITC/PI staining. [SEP]Relations: Netilmicin has relations: drug_drug with Epoprostenol, drug_drug with Epoprostenol, drug_drug with Apalutamide, drug_drug with Apalutamide, drug_drug with Dexpanthenol, drug_drug with Dexpanthenol, drug_drug with Pentostatin, drug_drug with Pentostatin, drug_drug with Sisomicin, drug_drug with Sisomicin. Definitions: endothelial progenitor cell defined as following: Cells derived from BONE MARROW that circulate in the adult bloodstream and possess the potential to proliferate and differentiate into mature ENDOTHELIAL CELLS.. quercetin defined as following: A flavonol widely distributed in plants. It is an antioxidant, like many other phenolic heterocyclic compounds. Glycosylated forms include RUTIN and quercetrin.. sperm defined as following: Mature male germ cells derived from SPERMATIDS. As spermatids move toward the lumen of the SEMINIFEROUS TUBULES, they undergo extensive structural changes including the loss of cytoplasm, condensation of CHROMATIN into the SPERM HEAD, formation of the ACROSOME cap, the SPERM MIDPIECE and the SPERM TAIL that provides motility.. cell surface defined as following: The external part of the cell wall and/or plasma membrane. [GOC:jl, GOC:mtg_sensu, GOC:sm]. nanoparticles defined as following: Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging.. annexin V defined as following: This gene is involved in anticoagulation processes and mediates lipid binding.. VEGF defined as following: The original member of the family of endothelial cell growth factors referred to as VASCULAR ENDOTHELIAL GROWTH FACTORS. Vascular endothelial growth factor-A was originally isolated from tumor cells and referred to as \"tumor angiogenesis factor\" and \"vascular permeability factor\". Although expressed at high levels in certain tumor-derived cells it is produced by a wide variety of cell types. In addition to stimulating vascular growth and vascular permeability it may play a role in stimulating VASODILATION via NITRIC OXIDE-dependent pathways. Alternative splicing of the mRNA for vascular endothelial growth factor A results in several isoforms of the protein being produced.. Surfactant protein A defined as following: An abundant pulmonary surfactant-associated protein that binds to a variety of lung pathogens, resulting in their opsinization. It also stimulates MACROPHAGES to undergo PHAGOCYTOSIS of microorganisms. Surfactant protein A contains a N-terminal collagen-like domain and a C-terminal lectin domain that are characteristic of members of the collectin family of proteins.. 7-aminoactinomycin defined as following: A fluorescent nucleic acid dye which selectively binds GC sequences in double-stranded DNA. It has a molecular weight of 1270.5, an absorbance maximun at 546 nm, and emission maximum at 647 nm. It is commonly used to discriminate viable from non-viable cells.. antibody defined as following: A protein complex that in its canonical form is composed of two identical immunoglobulin heavy chains and two identical immunoglobulin light chains, held together by disulfide bonds and sometimes complexed with additional proteins. An immunoglobulin complex may be embedded in the plasma membrane or present in the extracellular space, in mucosal areas or other tissues, or circulating in the blood or lymph. [GOC:add, GOC:jl, ISBN:0781765196]. Ki67 defined as following: This gene is involved in cellular proliferation.. Treg cells defined as following: CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.. phosphatidylserine defined as following: A phospholipid with a polar serine found in phosphoester linkage to diacylglycerol.. granulosa-lutein cells defined as following: A cell of the corpus luteum of the ovary that is derived from the granulosa cells of the preovulatory follicle; it secretes progesterone and estrogen.. apoptotic bodies defined as following: A vesicle containing parts of a dying cell. Apoptotic bodies can be formed during the execution phase of the apoptotic process, when the cell's cytoskeleton breaks up and causes the membrane to bulge outward. These bulges may separate from the cell, taking a portion of cytoplasm with them, to become apoptotic bodies. These are then engulfed by phagocytic cells, and their components recycled. Apoptotic bodies may range in size from 0.8 to 5um. [GOC:mtg_apoptosis, GOC:vesicles, PMID:15242875, PMID:24223256, Wikipedia:Apoptosis, Wikipedia:Bleb_(cell_biology)]. netilmicin defined as following: Semisynthetic 1-N-ethyl derivative of SISOMYCIN, an aminoglycoside antibiotic with action similar to gentamicin, but less ear and kidney toxicity.. PI defined as following: Backflow of blood from the PULMONARY ARTERY into the RIGHT VENTRICLE due to imperfect closure of the PULMONARY VALVE.. cytochalasin D defined as following: A fungal metabolite that blocks cytoplasmic cleavage by blocking formation of contractile microfilament structures resulting in multinucleated cell formation, reversible inhibition of cell movement, and the induction of cellular extrusion. Additional reported effects include the inhibition of actin polymerization, DNA synthesis, sperm motility, glucose transport, thyroid secretion, and growth hormone release.. cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. hCG defined as following: A sialoglycoprotein hormone secreted by the placenta and maintains the corpus luteum at the beginning of the gestation period.. proliferating cell nuclear antigen defined as following: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.. endothelial cell defined as following: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.. Atherosclerotic defined as following: status similar or related to atherosclerosis. propidium iodide defined as following: A fluorescent nucleic acid dye which binds only to double-stranded nucleic acids. It has a molecular weight of 668.4, an absorbance maximum of 535nm, and an emission maximum of 617 nm. It is commonly used to determine the DNA content of a cell or to discriminate viable from non-viable cells.. cytoskeletal defined as following: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.. CD105 defined as following: Endoglin (658 aa, ~71 kDa) is encoded by the human ENG gene. This protein plays a role in transforming growth factor receptor signaling.. ofloxacin defined as following: A synthetic fluoroquinolone antibacterial agent that inhibits the supercoiling activity of bacterial DNA GYRASE, halting DNA REPLICATION.. rabbits defined as following: Taxonomic family which includes rabbits and hares.. CD31 defined as following: Human PECAM1 wild-type allele is located within 17q23 and is approximately 64 kb in length. This allele, which encodes platelet endothelial cell adhesion molecule protein, plays a role in transendothelial migration of leukocytes, angiogenesis, integrin activation, and may inhibit platelet-collagen interactions.. germ cells defined as following: The reproductive cells in multicellular organisms at various stages during GAMETOGENESIS.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. PS defined as following:Supernumerary mandibular right central primary incisor
. MSCs defined as following: Enables the transmembrane transfer of an ion by a channel that opens in response to a mechanical stress and when a cyclic nucleotide has been bound by the channel complex or one of its constituent parts. [GOC:jl, PMID:22206667]. hypertension defined as following: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. ROS defined as following: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.. Annexin V defined as following: This gene is involved in anticoagulation processes and mediates lipid binding..", "label": "yes"} {"id": "converted_4296", "sentence1": "Is FKBP52 encoding a chaperone ?", "sentence2": "Hsp90 co-chaperones Pp5 and FKBPs, The co-chaperone FK506-binding protein 51 (FKBP51), co‑chaperone FKBP52 [SEP]Relations: tau protein binding has relations: molfunc_protein with FKBP4, molfunc_protein with FKBP4, molfunc_protein with PRKAA1, molfunc_protein with PRKAA1, molfunc_protein with TTBK1, molfunc_protein with TTBK1, molfunc_protein with GSK3B, molfunc_protein with GSK3B, molfunc_protein with CDK5, molfunc_protein with CDK5. Definitions: Hsp90 defined as following: Human HSP90AA1 wild-type allele is located in the vicinity of 14q32.33 and is approximately 59 kb in length. This allele, which encodes heat shock protein HSP 90-alpha, plays a role in both nitric oxide metabolism and protein folding. A chromosomal translocation t(3;14)(q27;q32) of this gene and the BCL6 gene is associated with B cell non-Hodgkin lymphoma.. FKBP51 defined as following: Human FKBP5 wild-type allele is located in the vicinity of 6p21.31 and is approximately 155 kb in length. This allele, which encodes peptidyl-prolyl cis-trans isomerase FKBP5 protein, is involved in the modulation of protein folding..", "label": "yes"} {"id": "converted_2434", "sentence1": "Is Tofacitinib effective for Ulcerative Colitis?", "sentence2": "Tofacitinib, inhibiting signalling via all Janus kinase family members, was effective in phase 2 and 3 trials in moderate-severe ulcerative colitis., Among them, Janus kinase (JAK) inhibitors seem to have the lead, since tofacitinib has received regulatory approval in 2012 for the treatment of rheumatoid arthritis, and also it has shown a favorable risk-benefit ratio in phase 3 studies for ulcerative colitis, both in anti-TNF naïve and anti-TNF experienced patients. , Near future conventional drug options include oral agents such as tofacitinib and mongersen. , Tofacitinib showed dose related efficacy for induction therapy. , Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis., BACKGROUND: Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial. , CONCLUSIONS: In patients with moderately to severely active ulcerative colitis, tofacitinib was more effective as induction and maintenance therapy than placebo., Tofacitinib (CP-690,550), an oral small-molecule Janus kinase inhibitor, has been shown to be effective in the treatment of rheumatoid arthritis, autoimmune encephalomyelitis and ulcerative colitis. , Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial., BACKGROUND: Tofacitinib, an oral, small-molecule Janus kinase inhibitor, was shown to have potential efficacy as induction therapy for ulcerative colitis in a phase 2 trial., Across all three trials, adjudicated nonmelanoma skin cancer occurred in five patients who received tofacitinib and in one who received placebo, and adjudicated cardiovascular events occurred in five who received tofacitinib and in none who received placebo; as compared with placebo, tofacitinib was associated with increased lipid levels.Cold weather can affect your body in different ways. You can get frostbite, which is an injury to the body that is caused by freezing. Your body can also lose heat faster than you can produce it. That can cause hypothermia, or abnormally low body temperature. It can make you sleepy, confused, and clumsy. Because it happens gradually and affects your thinking, you may not realize you need help. That makes it especially dangerous. A body temperature below 95 °F (35 °C) is a medical emergency and can lead to death if not treated promptly.
Anyone who spends much time outdoors in cold weather can get hypothermia. You can also get it from being cold and wet, or under cold water for too long. Babies and old people are especially at risk. Babies can get it from sleeping in a cold room.
Centers for Disease Control and Prevention
. WBCs defined as following: White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).. intracerebral hemorrhage defined as following: Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.. vasospasm defined as following: spasm of the blood vessels resulting in decrease in their caliber.. c-reactive protein defined as following: A plasma protein that circulates in increased amounts during inflammation and after tissue damage. C-Reactive Protein measured by more sensitive methods often for coronary heart disease risk assessment is referred to as High Sensitivity C-Reactive Protein (hs-CRP)..", "label": "yes"} {"id": "converted_1365", "sentence1": "Is Mammaprint approved by the United States Food and Drug Administration?", "sentence2": "an FDA-cleared 70-gene signature of MammaPrint panel , on MammaPrint, the first and only assay for breast cancer management that has been cleared by the FDA., The MammaPrint assay has the advantages of a 510(k) clearance by the US Food and Drug Administration, a larger gene number which may enhance further utility, and the potentially wider patient eligibility including lymph node-positive, ER-negative, , The MammaPrint assay has the advantages of a 510(k) clearance by the U.S. Food and Drug Administration, a larger gene number, which may enhance further utility, and a potentially wider patient eligibility, including lymph node-positive, estrogen receptor (ER)-negative, and younger patients being accrued into the prospective trial (Microarray in Node-Negative Disease May Avoid Chemotherapy). [SEP]Relations: benign neoplasm of male breast has relations: disease_disease with breast benign neoplasm, disease_disease with breast benign neoplasm. Definitions: MammaPrint defined as following: An in vitro molecular diagnostic test that uses gene expression profiling to analyze gene activity within a breast cancer tumor sample. It looks at the activity of 70 genes and is useful in assessing the likelihood of metastasis and recurrence.. breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. Mammaprint defined as following: An in vitro molecular diagnostic test that uses gene expression profiling to analyze gene activity within a breast cancer tumor sample. It looks at the activity of 70 genes and is useful in assessing the likelihood of metastasis and recurrence..", "label": "yes"} {"id": "converted_3157", "sentence1": "Is Apelin usually decreased in diabetes?", "sentence2": "Apelin has been shown to act on glucose and lipid metabolism but also to modulate insulin secretion. Moreover, different studies in both animals and humans have shown that plasma apelin concentrations are usually increased during obesity and type 2 diabetes., Upregulated expression of resistin, vaspin, apelin and TNF-α plays a significant role in induction of insulin resistance linked with obesity and type 2 diabetes., Moreover, different studies in both animals and humans have shown that plasma apelin concentrations are usually increased during obesity and type 2 diabetes., Apelin levels are increased in morbidly obese subjects with type 2 diabetes mellitus., In men at risk for diabetes (HbA1c 5.7-6.4%, FPG 100-125mg/dl, or OGTT-2h-PG 140-199mg/dl), the risk for developing diabetes was higher in those with higher plasma apelin concentration than in those with lower plasma apelin concentrations (10.6%/year vs. 5.1%/year, p<0.001).Chickens raised for egg production
. topoisomerase I defined as following: DNA TOPOISOMERASES that catalyze ATP-independent breakage of one of the two strands of DNA, passage of the unbroken strand through the break, and rejoining of the broken strand. DNA Topoisomerases, Type I enzymes reduce the topological stress in the DNA structure by relaxing the superhelical turns and knotted rings in the DNA helix.. camptothecin defined as following: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.. DNA-binding protein defined as following: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.. Chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. pre-mRNA defined as following: A primary RNA transcript synthesized from a DNA template in eukaryotic nuclei which is post-transcriptionally modified and spliced to produce a mature mRNA.. transcription factors defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young..", "label": "yes"} {"id": "converted_2665", "sentence1": "Is Lysyl oxidase crosslinking collagen?", "sentence2": "Lysyl oxidase (LOX) and LOX-like (LOXL) proteins play crucial roles in ECM remodeling due to their collagen crosslinking and intracellular functions. , Lysyl oxidase-like 1, a crosslinking enzyme implicated in collagen and elastin biogenesis, LOXL2 mediates collagen crosslinking, The same was true for assaying lysyl oxidase, an enzyme involved in crosslinking of matrix molecules., In addition, collagen fibers in metastatic lung tumors exhibit greater linearity and organization as a result of collagen crosslinking by the lysyl oxidase (LOX) family of enzymes. [SEP]Relations: protein-lysine 6-oxidase activity has relations: molfunc_protein with LOXL2, molfunc_protein with LOXL2, molfunc_protein with LOXL4, molfunc_protein with LOXL4, molfunc_protein with LOXL1, molfunc_protein with LOXL1, molfunc_protein with LOX, molfunc_protein with LOX, molfunc_protein with LOXL3, molfunc_protein with LOXL3. Definitions: LOX defined as following: Protein-lysine 6-oxidase (417 aa, ~47 kDa) is encoded by the human LOX gene. This protein plays a role in both lysine metabolism and the formation of cross-links in extracellular matrix proteins.. lysyl oxidase defined as following: An enzyme oxidizing peptidyl-lysyl-peptide in the presence of water & molecular oxygen to yield peptidyl-allysyl-peptide plus ammonia & hydrogen peroxide. EC 1.4.3.13.. lung tumors defined as following: Tumors or cancer of the LUNG.. Lysyl oxidase defined as following: This gene plays a role in cross-linking extracellular matrix proteins.. LOXL2 defined as following: This gene is involved in protein crosslinking.. ECM defined as following: Human MMRN1 wild-type allele is located in the vicinity of 4q22 and is approximately 75 kb in length. This allele, which encodes multimerin-1 protein, plays a role in platelet factor V/Va homeostasis.. collagen defined as following: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH)..", "label": "yes"} {"id": "converted_2342", "sentence1": "Does DDX54 play a role in DNA damage response?", "sentence2": "DDX54 regulates transcriptome dynamics during DNA damage response., The contribution of post-transcriptional gene regulatory networks to the DNA damage response (DDR) has not been extensively studied. Here, we systematically identified RNA-binding proteins differentially interacting with polyadenylated transcripts upon exposure of human breast carcinoma cells to ionizing radiation (IR). Interestingly, more than 260 proteins, including many nucleolar proteins, showed increased binding to poly(A)+RNA in IR-exposed cells. The functional analysis of DDX54, a candidate genotoxic stress responsive RNA helicase, revealed that this protein is an immediate-to-early DDR regulator required for the splicing efficacy of its target IR-induced pre-mRNAs. Upon IR exposure, DDX54 acts by increased interaction with a well-defined class of pre-mRNAs that harbor introns with weak acceptor splice sites, as well as by protein-protein contacts within components of U2 snRNP and spliceosomal B complex, resulting in lower intron retention and higher processing rates of its target transcripts. Because DDX54 promotes survival after exposure to IR, its expression and/or mutation rate may impact DDR-related pathologies. Our work indicates the relevance of many uncharacterized RBPs potentially involved in the DDR., The functional analysis of DDX54, a candidate genotoxic stress responsive RNA helicase, revealed that this protein is an immediate-to-early DDR regulator required for the splicing efficacy of its target IR-induced pre-mRNAs.[SEP]Relations: protein binding has relations: molfunc_protein with DDX55, molfunc_protein with DDX55, molfunc_protein with DDX5, molfunc_protein with DDX5, molfunc_protein with DDX6, molfunc_protein with DDX6, molfunc_protein with DDX60, molfunc_protein with DDX60, molfunc_protein with DDX42, molfunc_protein with DDX42. Definitions: DDR defined as following: Human DDR1 wild-type allele is located in the vicinity of 6p21.3 and is approximately 345 kb in length. This allele, which encodes epithelial discoidin domain-containing receptor 1 protein, is involved in the regulation of cell growth, differentiation and metabolism.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. spliceosomal B complex defined as following: Organelles in which the splicing and excision reactions that remove introns from precursor messenger RNA molecules occur. One component of a spliceosome is five small nuclear RNA molecules (U1, U2, U4, U5, U6) that, working in conjunction with proteins, help to fold pieces of RNA into the right shapes and later splice them into the message.. introns defined as following: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. RNA-binding proteins defined as following: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA..", "label": "yes"} {"id": "converted_3241", "sentence1": "Can Enlimomab improve stroke outcomes?", "sentence2": "Treatment with a murine anti-ICAM-1 antibody (enlimomab) has been investigated in patients with acute ischemic stroke in the Enlimomab Acute Stroke Trial (EAST). Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group., The two clinical trials of therapy aimed at limiting the inflammatory response in acute stroke that have been carried out to date, however, have not shown a benefit to such therapy. , en classes of neuroprotective agents have reached phase III efficacy trials but have shown mixed results. They included calcium channel antagonists, NMDA receptor antagonists, lubeluzole, CDP-choline, the free radical scavenger tirilazad and ebselen, enlimomab, GABA agonist clomethiazole, the sodium channel antagonist fosphenytoin, magnesium, glycine site antagonist GV150526 and piracetam. , BACKGROUND AND PURPOSE: Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial. , Examination of several potential mechanisms for the negative outcome in a clinical stroke trial of enlimomab, a murine anti-human intercellular adhesion molecule-1 antibody: a bedside-to-bench study., ESULTS: At day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004). Fewer patients had symptom-free recovery on enlimomab than placebo (p = 0.004), and more died (22.2 versus 16.2%). The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005). There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever., CONCLUSIONS: The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome., CONCLUSIONS\n\nThe authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome., There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever., RESULTS\n\nAt day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004)., The negative effect of enlimomab was apparent on days 5, 30, and 90 of treatment (p = 0.005)., However, this treatment failed to show benefit in the Enlimomab Acute Stroke Trial., There were significantly more adverse events with enlimomab treatment than placebo, primarily infections and fever., These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke., RESULTS\nAt day 90, the Modified Rankin Scale score was worse in patients treated with enlimomab than with placebo (p = 0.004)., Unfortunately, the case fatality rate in this trial was significantly higher in the enlimomab patient group than in the placebo group., CONCLUSIONS\nDoses of enlimomab between 140 and 480 mg administered over 5 days did not increase the risk of adverse events in patients with ischaemic or haemorrhagic stroke during an observation period of 30 +/- 10 days., PURPOSE: Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial., These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke., Enlimomab, a murine monoclonal anti-human intercellular adhesion molecule (ICAM)-1 antibody, had a negative outcome in a multicenter acute-stroke trial., These observations provide several possible mechanisms for central nervous system-related clinical deterioration that occurred when Enlimomab was given in acute ischemic stroke., The authors conclude that anti-ICAM therapy with enlimomab is not an effective treatment for ischemic stroke in the model studied and, indeed, may significantly worsen stroke outcome.[SEP]Relations: Ischemic stroke has relations: drug_effect with Celecoxib, drug_effect with Celecoxib, drug_effect with Celecoxib, drug_effect with Celecoxib, drug_effect with Pazopanib, drug_effect with Pazopanib, drug_effect with Pazopanib, drug_effect with Pazopanib, drug_effect with Sitaxentan, drug_effect with Sitaxentan. Definitions: Doses defined as following: A quantity of an agent (such as substance or energy) administered, taken, or absorbed at one time.. ebselen defined as following: A organoselenium compound with anti-inflammatory, anti-oxidant and cytoprotective activity. Ebselen acts as a glutathione peroxidase mimetic and is thereby able to prevent cellular damage induced by reactive oxygen species (ROS). In addition, this agent inhibits the activity of a variety of enzymes including nitric oxide synthase (NOS), 5-lipoxygenase, cyclooxygenase, protein kinase C (PKC), NADPH oxidase and gastric H+/K+-ATPase. Furthermore, ebselen may be neuroprotective due to its ability to neutralize free radicals upon NMDA receptor activation thus, reducing lipoperoxidation mediated by glutamate-induced excitotoxicity.. CDP-choline defined as following: Donor of choline in biosynthesis of choline-containing phosphoglycerides.. ischemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue.. NMDA receptor defined as following: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.. stroke defined as following: A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810). clomethiazole defined as following: A sedative and anticonvulsant often used in the treatment of alcohol withdrawal. Chlormethiazole has also been proposed as a neuroprotective agent. The mechanism of its therapeutic activity is not entirely clear, but it does potentiate GAMMA-AMINOBUTYRIC ACID receptors response and it may also affect glycine receptors.. sodium channel defined as following: Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.. fosphenytoin defined as following: A water-soluble phosphate ester prodrug of phenytoin, a hydantoin derivative with anticonvulsant activity. Fosphenytoin is hydrolyzed to phenytoin by phosphatases. Phenytoin exerts its effect mainly by promoting sodium efflux and stabilizes neuronal membranes in the motor cortex. This leads to a suppression of excessive neuronal firing and limits the spread of seizure activity.. murine defined as following: Any of numerous species of small rodents belonging to the genus Mus and various related genera of the family Muridae.. piracetam defined as following: A compound suggested to be both a nootropic and a neuroprotective agent..", "label": "no"} {"id": "converted_3058", "sentence1": "Is Miller-Dieker syndrome associated with abnormalities of chromosome 1?", "sentence2": "A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion). , Chromosome microdeletions within 17p13.3 can result in either isolated lissencephaly sequence (ILS) or Miller-Dieker syndrome (MDS). , We report a fetus with lissencephaly diagnosed as Miller-Dieker Syndrome postnatally. G banded chromosome analysis revealed 45,X,psu dic(17;Y)(p13;p11.32).ish dic (17;Y)(LIS1-,RARA+, SRY+, DYZ3+) by G-banding analysis using high resolution banding technique. Fetal delayed cortical development will be the findings to perform further investigations including fluorescence in situ hybridization analysis for MDS, a 17p13.3 microdeletion syndrome, pre/postnatally. This will be the first case of MDS with unbalanced translocation between deleted short arm of chromosome 17 and Y chromosome., We report the finding of a 2.5-Mb gene region quadruplication of Chromosome 17p13.3. This region is well characterized for the deletion leading to Miller-Dieker syndrome but has an unclear replication phenotype. , Both deletions have overlapped with the critical region of Miller-Dieker syndrome (MDS) and involved candidate genes such as PAFAH1B1, YWHAE and CRK. In addition, SNP array and FISH analyses on the parental peripheral blood samples demonstrated that both 17p13.3 and 17p13.3p13.2 deletions were of de novo origin., Miller-Dieker syndrome (MDS) is caused by a heterozygous deletion of chromosome 17p13.3 involving the genes LIS1 and YWHAE (coding for 14.3.3ε) and leads to malformations during cortical development., We studied after death a 3-month-old girl whose karyotype was 45,XX,-15,-17,+der(17),t(15;17)(q13;p13.3) and thus combines abnormalities of chromosome 15 associated with the Prader-Willi syndrome and of chromosome 17 associated with the Miller-Dieker syndrome., The Miller-Dieker syndrome (MDS), a syndrome with lissencephaly, distinctive craniofacial features, growth impairment, and profound developmental failure, has been associated with a deletion of the distal part of chromosome band 17p13., The Miller-Dieker syndrome (type I lissencephaly) is a neuronal migration disorder which is associated with microdeletions in the short arm of chromosome 17., Detection of submicroscopic deletions in band 17p13 in patients with the Miller-Dieker syndrome., A 15-month-old girl with Miller-Dieker syndrome, a contiguous gene deletion syndrome involving chromosome 17p13.3 and resulting in lissencephaly, was diagnosed with precursor B-cell acute lymphoblastic leukemia., A computed tomography scan revealed evidence of lissencephaly, and chromosomal analysis showed a microdeletion on the short arm of chromosome 17 (17p13.3), confirming the diagnosis as Miller-Dieker syndrome., Familial Miller-Dieker syndrome associated with pericentric inversion of chromosome 17., The Miller-Dieker syndrome (MDS), a rare congenital disorder manifested by characteristic facial abnormalities and lissencephaly (smooth brain), is associated with microdeletions of the distal 17p region., Miller-Dieker syndrome (MDS), a disorder manifesting the severe brain malformation lissencephaly (\"smooth brain\"), is caused, in the majority of cases, by a chromosomal microdeletion of the distal short arm of chromosome 17., The Miller-Dieker syndrome (MDS), composed of characteristic facial abnormalities and a severe neuronal migration disorder affecting the cerebral cortex, is caused by visible or submicroscopic deletions of chromosome band 17p13., Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment., Identification of the functional profilin gene, its localization to chromosome subband 17p13.3, and demonstration of its deletion in some patients with Miller-Dieker syndrome., HIC1 is a candidate tumor suppressor gene which is frequently hypermethylated in human tumors, and its location within the Miller-Dieker syndrome's critical deletion region at chromosome 17p13.3 makes it a candidate gene for involvement in this gene deletion syndrome., A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion)., About 15% of patients with isolated lissencephaly and more than 90% of patients with Miller-Dieker syndrome have microdeletions in a critical 350-kilobase region in chromosome 17p13.3 (ref., Chromosome aberrations in which epilepsy is a major and consistent finding include Angelman syndrome due to loss of the maternal 15q11.2-q12 segment, tetrasomy of the maternal segment 15pter-q13 due to an additional inv dup chromosome, Miller-Dieker syndrome due to deletion of the 17p13.3 segment including the lissencephaly1 gene, ring chromosome 20, and Wolf-Hirschhorn syndrome due to deletion of at least the 4p16.3 segment., Miller-Dieker syndrome and trisomy 5p in a child carrying a derivative chromosome with a microdeletion in 17p13.3 telomeric to the LIS1 and the D17S379 loci., The Miller-Dieker syndrome, a disorder of neuronal migration, is caused by deletions of chromosome 17p13.3., The girl was diagnosed by subtelomeric FISH and array-CGH, showing a 4.43-Mb heterozygous deletion on chromosome 10p that involved 14 genes and a 3.22-Mb single-copy gain on chromosome 17p, which includes the critical region of the Miller-Dieker syndrome and 61 genes., Detection of submicroscopic deletions in band 17p13 in patients with the Miller-Dieker syndrome.The Miller-Dieker syndrome (MDS), a syndrome with lissencephaly, distinctive craniofacial features, growth impairment, and profound developmental failure, has been associated with a deletion of the distal part of chromosome band 17p13. , Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment.Microdeletions of chromosome 17p13.3 involving YWHAE present with growth restriction, craniofacial dysmorphisms, structural abnormalities of brain and cognitive impairment. , Unbalanced translocation (15;17)(q13;13.3) with apparent Prader-Willi syndrome but without Miller-Dieker syndrome.We studied after death a 3-month-old girl whose karyotype was 45,XX,-15,-17,+der(17),t(15;17)(q13;p13.3) and thus combines abnormalities of chromosome 15 associated with the Prader-Willi syndrome and of chromosome 17 associated with the Miller-Dieker syndrome. , The Miller-Dieker syndrome (MDS), a rare congenital disorder manifested by characteristic facial abnormalities and lissencephaly (smooth brain), is associated with microdeletions of the distal 17p region. , A revision of the lissencephaly and Miller-Dieker syndrome critical regions in chromosome 17p13.3.Miller-Dieker syndrome (MDS) is a multiple malformation syndrome characterized by classical lissencephaly and a characteristic facies. , Case Report of Proliferative Peripheral Retinopathy in Two Familial Lissencephaly Infants with Miller-Dieker Syndrome.A complete ophthalmic examination is not routinely performed on infants with Miller-Dieker syndrome (MDS, chromosome 17p13.3 microdeletion). , Identification of the functional profilin gene, its localization to chromosome subband 17p13.3, and demonstration of its deletion in some patients with Miller-Dieker syndrome.Profilin is a conserved actin-monomer-binding protein which is found in all eukaryotes, including yeast. , We propose that essentially no loss of 17p material has occurred and confirm previous reports that the critical region for the production of the Miller-Dieker phenotype is located subterminally in the 17p13.3 region.Mandibular left third molar prosthesis
. Profilin defined as following: This gene plays a role in the regulation of actin polymerization.. 4p16.3 defined as following: A chromosome band present on 4p. neuronal migration disorder defined as following: A diverse group of congenital brain developmental disorders characterized by defects in neuronal migration in the brain during early fetal development. The neuronal migration defects result in brain abnormalities that are usually manifested with mental retardation and epilepsy.. Angelman syndrome defined as following: A syndrome characterized by multiple abnormalities, MENTAL RETARDATION, and movement disorders. Present usually are skull and other abnormalities, frequent infantile spasms (SPASMS, INFANTILE); easily provoked and prolonged paroxysms of laughter (hence \"happy\"); jerky puppetlike movements (hence \"puppet\"); continuous tongue protrusion; motor retardation; ATAXIA; MUSCLE HYPOTONIA; and a peculiar facies. It is associated with maternal deletions of chromosome 15q11-13 and other genetic abnormalities. (From Am J Med Genet 1998 Dec 4;80(4):385-90; Hum Mol Genet 1999 Jan;8(1):129-35). deletions defined as following: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.. Y chromosome defined as following: The male sex chromosome, being the differential sex chromosome carried by half the male gametes and none of the female gametes in humans and in some other male-heterogametic species in which the homologue of the X chromosome has been retained.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. Prader-Willi syndrome defined as following: An autosomal dominant disorder caused by deletion of the proximal long arm of the paternal chromosome 15 (15q11-q13) or by inheritance of both of the pair of chromosomes 15 from the mother (UNIPARENTAL DISOMY) which are imprinted (GENETIC IMPRINTING) and hence silenced. Clinical manifestations include MENTAL RETARDATION; MUSCULAR HYPOTONIA; HYPERPHAGIA; OBESITY; short stature; HYPOGONADISM; STRABISMUS; and HYPERSOMNOLENCE. (Menkes, Textbook of Child Neurology, 5th ed, p229). death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. trisomy 5p defined as following: Duplication of the short arm of chromosome 5 most frequently associated with craniofacial, cardiac, renal, and limb abnormalities, and moderate to severe mental retardation. Dandy-Walker malformation (agenesis of the cerebellar vermis, hydrocephalus, and posterior fossa cyst continuous with the fourth ventricle) occurs in some cases. The phenotype is related to the amount of genetic material duplicated and the specific duplicated segment.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. Wolf-Hirschhorn syndrome defined as following: A syndrome caused by large deletions of the telomereic end of the short arm of CHROMOSOME 4 (4p) in Wolf-Hirchhorn syndrome critial regions (WHSCRs). Several candidate genes have been identified including WHSC1 and WHSCH2 which appear to be responsible for the core phenotype and in combination with other linked and unlinked genes determine the severity and inclusion of rarer phenotypes. Most cases have a characteristic cranio-facial defect often referred to as \"Greek helmet face\" - a combined result of MICROCEPHALY, broad forehead, prominent glabella, HYPERTELORISM, high arched eyebrows, short philtrum and micrognathia. In addition there is mental retardation, growth delays, EPILEPSY, and frequently a wide range of midline and skeletal defects, including HYPOSPADIAS; CONGENITAL HEART DEFECTS; CLEFT LIP; CLEFT PALATE; colobomata; CLUBFOOT; clinodactyly; SCOLIOSIS; and KYPHOSIS.. lissencephaly defined as following: A lissencephaly syndrome characterized by smoothness of the surface of the brain (lissencephaly type I) with thickening of the cerebral cortex (pachygyria), absence of gyri and sulci (agyria), microcephaly, mental retardation, low sloping forehead, and prominent nasal bridge.. eukaryotes defined as following: Organism or cells with a nucleus separated from the cytoplasm by a two membrance nuclear envelope and compartmentalization of function into distinct cytoplasmic organelles.. ring chromosome 20 defined as following: A rare condition in which the two arms of chromosome 20 are fused resulting in a ring chromosome. It is characterized by recurrent seizures with an onset in childhood. Additional features my include microcephaly and short stature.. chromosome 17 defined as following: A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.. human defined as following: Members of the species Homo sapiens.. chromosome 17p defined as following: Proximal (short) arm of chromosome 17. MDS defined as following: A rare syndrome caused by deletion of genetic material in the short arm of chromosome 17. It is characterized by an abnormally smooth brain with fewer folds and grooves. It results in intellectual disability, developmental delay, seizures, spasticity, hypotonia, and feeding difficulties. Affected individuals have distinctive facial features that include a prominent forehead, midface hypoplasia, small, upturned nose, low-set ears, small jaw, and thick upper lip.. congenital disorder defined as following: existing at, and usually before, birth; referring to conditions that are present at birth, regardless of their causation; inborn metabolism disorders are generally not treed here.. Miller-Dieker syndrome defined as following: A rare syndrome caused by deletion of genetic material in the short arm of chromosome 17. It is characterized by an abnormally smooth brain with fewer folds and grooves. It results in intellectual disability, developmental delay, seizures, spasticity, hypotonia, and feeding difficulties. Affected individuals have distinctive facial features that include a prominent forehead, midface hypoplasia, small, upturned nose, low-set ears, small jaw, and thick upper lip.. chromosome 1 defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification..", "label": "no"} {"id": "converted_2282", "sentence1": "Is dasatinib effective for treatment of glioblastoma?", "sentence2": "RESULTS: fourteen randomized clinical trials were identified (7 with bevacizumab, 2 cilengitide, 1 enzastaurin, 1 dasatinib, 1 vandetanib, 1 temsirolimus, 1 cediranib) including 4330 patients. Antiangiogenic drugs showed no improvement in overall survival with a pooled HR of 1.00, a trend for an inferior outcome, in terms of overall survival, was observed in the group of patients receiving antiangiogenic drug alone compared to cytotoxic drug alone (HR=1.24, p=0.056)., CONCLUSIONS: Intraparticipant dose escalation was feasible, but dasatinib was ineffective in recurrent GBM. , Median progression-free survival (PFS) was 1.35 months (95% confidence interval: 1.2-1.4) and 6-month PFS was 7.7%. In this phase I study of recurrent glioblastoma patients, the combination of CCNU and dasatinib showed significant hematological toxicities and led to suboptimal exposure to both agents., Dasatinib in conjunction with bevacizumab does not appear to have activity in patients with recurrent, heavily pretreated GBM.[SEP]Relations: Dasatinib has relations: drug_effect with Eczema, drug_effect with Eczema, drug_effect with Pain, drug_effect with Pain, drug_effect with Erythema, drug_effect with Erythema, drug_effect with Edema, drug_effect with Edema, drug_effect with Myalgia, drug_effect with Myalgia. Definitions: Dasatinib defined as following: An orally bioavailable synthetic small molecule-inhibitor of SRC-family protein-tyrosine kinases. Dasatinib binds to and inhibits the growth-promoting activities of these kinases. Apparently because of its less stringent binding affinity for the BCR-ABL kinase, dasatinib has been shown to overcome the resistance to imatinib of chronic myeloid leukemia (CML) cells harboring BCR-ABL kinase domain point mutations. SRC-family protein-tyrosine kinases interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways; tumorigenic forms can occur through altered regulation or expression of the endogenous protein and by way of virally-encoded kinase genes.. glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO). vandetanib defined as following: An orally bioavailable 4-anilinoquinazoline. Vandetanib selectively inhibits the tyrosine kinase activity of vascular endothelial growth factor receptor 2 (VEGFR2), thereby blocking VEGF-stimulated endothelial cell proliferation and migration and reducing tumor vessel permeability. This agent also blocks the tyrosine kinase activity of epidermal growth factor receptor (EGFR), a receptor tyrosine kinase that mediates tumor cell proliferation and migration and angiogenesis.. bevacizumab defined as following: An anti-VEGF humanized murine monoclonal antibody. It inhibits VEGF RECEPTORS and helps to prevent PATHOLOGIC ANGIOGENESIS.. GBM defined as following: A sheet of amorphous extracellular material upon which the basal surfaces of epithelial cells rest and is the covering surface of a glomerular capillary, interposed between the cellular elements and the underlying connective tissue.. temsirolimus defined as following: An ester analog of rapamycin. Temsirolimus binds to and inhibits the mammalian target of rapamycin (mTOR), resulting in decreased expression of mRNAs necessary for cell cycle progression and arresting cells in the G1 phase of the cell cycle. mTOR is a serine/threonine kinase which plays a role in the PI3K/AKT pathway that is upregulated in some tumors.. cilengitide defined as following: A cyclic Arg-Gly-Asp peptide with potential antineoplastic activity. Cilengitide binds to and inhibits the activities of the alpha(v)beta(3) and alpha(v)beta(5) integrins, thereby inhibiting endothelial cell-cell interactions, endothelial cell-matrix interactions, and angiogenesis. (NCI04). toxicities defined as following: The finding of bodily harm due to the poisonous effects of something.. dasatinib defined as following: An orally bioavailable synthetic small molecule-inhibitor of SRC-family protein-tyrosine kinases. Dasatinib binds to and inhibits the growth-promoting activities of these kinases. Apparently because of its less stringent binding affinity for the BCR-ABL kinase, dasatinib has been shown to overcome the resistance to imatinib of chronic myeloid leukemia (CML) cells harboring BCR-ABL kinase domain point mutations. SRC-family protein-tyrosine kinases interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways; tumorigenic forms can occur through altered regulation or expression of the endogenous protein and by way of virally-encoded kinase genes..", "label": "no"} {"id": "converted_745", "sentence1": "Is rivaroxaban metabolized in kidneys?", "sentence2": "The novel oral anticoagulants (i.e., dabigatran, apixaban, rivaroxaban) all undergo renal metabolism to varying degrees, and hence dosing, efficacy, and safety require special consideration in CKD patients., The new oral anticoagulants have relatively little data in patients with severe renal impairment, and all have an element of renal excretion., Now new anticoagulant drugs(dabigatran and rivaroxaban) can become available. Therefore, we have to learn how to use those drugs. They have to carefully be used because they discharge from kidney and old aged patients have potential renal dysfunction. , In the everyday practice it will be necessary to be very cautious in patients with impaired renal function, as all these drugs are eliminated by kidneys., Dabigatran etexilate and rivaroxaban carry the highest risk due to a high degree of renal excretion, whereas the risk for apixaban, edoxaban and betrixaban seems lower., However, all these agents undergo renal clearance to varying degrees, and hence dosing, efficacy, and safety require special consideration in patients with CKD. , Rivaroxaban being excreted via kidney and liver, some precautions should apply in case of liver insufficiency. , Rivaroxaban elimination is mainly renal, but also through faecal matter and by hepatic metabolism. [SEP]Relations: Rivaroxaban has relations: contraindication with kidney disease, contraindication with kidney disease, drug_drug with Carboplatin, drug_drug with Carboplatin, drug_drug with Conjugated estrogens, drug_drug with Conjugated estrogens, drug_drug with Colistin, drug_drug with Colistin, drug_drug with Metaxalone, drug_drug with Metaxalone. Definitions: rivaroxaban defined as following: An orally bioavailable oxazolidinone derivative and direct inhibitor of the coagulation factor Xa with anticoagulant activity. Upon oral administration, rivaroxaban selectively binds to both free factor Xa and factor Xa bound in the prothrombinase complex. This interferes with the conversion of prothrombin (factor II) to thrombin and eventually prevents the formation of cross-linked fibrin clots. Rivaroxaban does not affect existing thrombin levels.. CKD defined as following: Impairment of the renal function secondary to chronic kidney damage persisting for three or more months.. renal defined as following: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.. liver insufficiency defined as following: The inability of the liver to perform its normal synthetic and metabolic functions.. impaired renal function defined as following: Diminished kidney function.. edoxaban defined as following: An orally active inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Edoxaban is administered as edoxaban tosylate. This agent has an elimination half-life of 9-11 hours and undergoes renal excretion.. apixaban defined as following: An orally active inhibitor of coagulation factor Xa with anticoagulant activity. Apixaban directly inhibits factor Xa, thereby interfering with the conversion of prothrombin to thrombin and preventing formation of cross-linked fibrin clots.. dabigatran defined as following: A THROMBIN inhibitor which acts by binding and blocking thrombogenic activity and the prevention of thrombus formation. It is used to reduce the risk of stroke and systemic EMBOLISM in patients with nonvalvular atrial fibrillation.. betrixaban defined as following: An orally active inhibitor of coagulation factor Xa (activated factor X) with anticoagulant activity. Betrixaban is primarily excreted unchanged in the bile and has a half life of about 19 hours..", "label": "yes"} {"id": "converted_2263", "sentence1": "Is scuba diving safe during pregnancy?", "sentence2": "Scuba diving is contraindicated., Overall, the women did not conduct enough dives per pregnancy, therefore no significant correlation between diving and fetal abnormalities could be established. These data indicate women are increasingly observing the diving industry recommendation and refraining from diving while pregnant. , Scuba diving also should be avoided throughout pregnancy because the fetus is at an increased risk for decompression sickness during this activity., Scuba diving also should be avoided throughout pregnancy because the fetus is at an increased risk for decompression sickness during this activity., Scuba diving also should be avoided throughout pregnancy because the fetus is at an increased risk for decompression sickness during this activity. , The different international federations and the Undersea and Hyperbaric Medical Society advise against scuba diving for pregnant women or those planning a pregnancy, but no randomized trials or trials provide a solid scientific basis. , Pregnant women are recommended not to dive, because the risk of birth defects seems to be greater among those who do, and there is a serious risk of fetal decompression disease. , The different international federations and the Undersea and Hyperbaric Medical Society advise against scuba diving for pregnant women or those planning a pregnancy, but no randomized trials or trials provide a solid scientific basis., Scuba diving also should be avoided throughout pregnancy because the fetus is at an increased risk for decompression sickness during this activity., Snorkeling can still be practiced during pregnancy, but scuba diving should be discontinued until after the birth period., Snorkeling can still be practiced during pregnancy, but scuba diving should be discontinued until after the birth period..[SEP]Relations: congenital abnormality has relations: disease_disease with Zika virus congenital syndrome, disease_disease with Zika virus congenital syndrome, disease_disease with developmental defect during embryogenesis, disease_disease with developmental defect during embryogenesis, disease_disease with Klippel-Feil syndrome, disease_disease with Klippel-Feil syndrome, disease_disease with congenital radioulnar synostosis, disease_disease with congenital radioulnar synostosis, disease_disease with cryptorchidism (disease), disease_disease with cryptorchidism (disease). Definitions: birth defects defined as following: Malformations of organs or body parts during development in utero..", "label": "no"} {"id": "converted_4273", "sentence1": "Is tofacitinib a JAK inhibitor?", "sentence2": "The Janus Kinase inhibitor tofacitinib impacts human dendritic cell differentiation and favours M1 macrophage development., Tofacitinib, a small JAK inhibitor, is approved for the treatment of RA and has demonstrated good efficacy in psoriasis phase III clinical trials. [SEP]Relations: Tofacitinib has relations: drug_protein with JAK2, drug_protein with JAK2, drug_protein with JAK1, drug_protein with JAK1, drug_protein with JAK3, drug_protein with JAK3, drug_drug with Briakinumab, drug_drug with Briakinumab, drug_drug with Tocilizumab, drug_drug with Tocilizumab. Definitions: JAK defined as following: A family of intracellular tyrosine kinases that participate in the signaling cascade of cytokines by associating with specific CYTOKINE RECEPTORS. They act upon STAT TRANSCRIPTION FACTORS in signaling pathway referred to as the JAK/STAT pathway. The name Janus kinase refers to the fact the proteins have two phosphate-transferring domains.. RA defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. Tofacitinib defined as following: An orally available inhibitor of Janus kinases (JAK), with immunomodulatory and anti-inflammatory activities. Upon administration, tofacitinib binds to JAK and prevents the activation of the JAK-signal transducers and activators of transcription (STAT) signaling pathway. This may decrease the production of pro-inflammatory cytokines, such as interleukin (IL)-6, -7, -15, -21, interferon-alpha and -beta, and may prevent both an inflammatory response and the inflammation-induced damage caused by certain immunological diseases. JAK kinases are intracellular enzymes involved in signaling pathways affecting hematopoiesis, immunity and inflammation.. psoriasis defined as following: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.. M1 macrophage defined as following: A macrophage that expresses CD80 and CD86 on the cell surface, produces high levels of interleukin (IL)-8 and IL-12 and converts arginine to nitric oxide. These cells promote inflammation.. tofacitinib defined as following: An orally available inhibitor of Janus kinases (JAK), with immunomodulatory and anti-inflammatory activities. Upon administration, tofacitinib binds to JAK and prevents the activation of the JAK-signal transducers and activators of transcription (STAT) signaling pathway. This may decrease the production of pro-inflammatory cytokines, such as interleukin (IL)-6, -7, -15, -21, interferon-alpha and -beta, and may prevent both an inflammatory response and the inflammation-induced damage caused by certain immunological diseases. JAK kinases are intracellular enzymes involved in signaling pathways affecting hematopoiesis, immunity and inflammation..", "label": "yes"} {"id": "converted_3186", "sentence1": "Are there any anti-amyloid antibody approved as drug for Alzheimer's disease treatment?", "sentence2": "Treatment with memantine, a noncompetitive NMDA receptor antagonist which is an approved drug for treatment of Alzheimer's disease, rescued protein phosphatase-2A activity by decreasing its demethylation at Leu309 selectively and attenuated Alzheimer's disease-like pathology and cognitive impairment in adeno-associated virus vector-1-I1PP2A rats. , anti-Amyloid agents (13.30%), no new drugs have been approved during the past 15 years; and the available medications are not cost-effective. [SEP]Relations: familial Alzheimer disease has relations: disease_disease with Alzheimer disease, disease_disease with Alzheimer disease, disease_protein with PRNP, disease_protein with PRNP, disease_phenotype_positive with Attention deficit hyperactivity disorder, disease_phenotype_positive with Attention deficit hyperactivity disorder, disease_disease with inherited prion disease, disease_disease with inherited prion disease, disease_phenotype_positive with Anxiety, disease_phenotype_positive with Anxiety. Definitions: drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. memantine defined as following: AMANTADINE derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent..", "label": "no"} {"id": "converted_2462", "sentence1": "Can radius fracture cause carpal tunnel syndrome?", "sentence2": "Carpal tunnel syndrome (CTS) after distal radius fractures can present in 3 forms: acute, transient, and delayed., Complications were categorized as carpal tunnel syndrome, other sensibility issues, tendon complications including irritation and rupture, deep infections, complex regional pain syndrome and unidentified DRUJ or scapholunar problems., The overall complication rate was 14.6% (95% CI 11.8-17.7) including carpal tunnel syndrome or change in sensibility in 5.2% and tendon complications in 4.7%. , BACKGROUND: Although median nerve neuropathy and carpal tunnel syndrome (CTS) are known complications of both untreated and acutely treated distal radius fracture, median neuropathy after correction of distal radius malunion is not commonly reported in hand surgery literature. , Complications were defined as malunion, carpal tunnel syndrome, complex regional pain syndrome (CRPS), persistent pain, and subjective cosmetic deformity of the wrist., Carpal tunnel syndrome is a common complication associated with distal radius fractures., The patient also had minor complications of little finger flexor tendon irritation and carpal tunnel syndrome. She underwent implant removal and carpal tunnel release at 8 months., Acute multiple flexor tendon injury and carpal tunnel syndrome after open distal radius fracture., Carpal tunnel syndrome is a common condition and is a well-recognized phenomenon following a distal radius fracture., We report the incidence of late onset post-operative carpal tunnel syndrome (late carpal tunnel syndrome) and late median nerve neuropathy after volar plating of distal radius fracture by conducting a retrospective study on volar plating for distal radius fracture performed during 2002 to 2006., Carpal tunnel syndrome after distal radius fracture., [Case-control study on transverse carpal ligament resection for the prevention of delayed carpal tunnel syndrome after distal radius fracture]., Hand numbness and carpal tunnel syndrome after volar plating of distal radius fracture., Delayed carpal tunnel syndrome presenting after a distal radius fracture has healed is best managed in standard fashion., Being well known and accepted techniques of carpal tunnel release, we believe that the techniques described in this paper provide a viable alternative for carpal tunnel release in the setting of distal radius fracture fixation; with the added advantages of the original minimally invasive techniques., Carpal tunnel syndrome after fracture of the distal radius is a well known complication in adults, but in small children carpal tunnel syndrome is extremely rare., Carpal Tunnel Syndrome and Distal Radius Fractures., Carpal tunnel syndrome after distal radius fracture., Hand numbness and carpal tunnel syndrome after volar plating of distal radius fracture.[SEP]Relations: carpal tunnel syndrome has relations: disease_disease with nerve compression syndrome, disease_disease with nerve compression syndrome, disease_disease with nerve compression syndrome, disease_disease with nerve compression syndrome, disease_disease with genetic peripheral neuropathy, disease_disease with genetic peripheral neuropathy, disease_disease with genetic peripheral neuropathy, disease_disease with genetic peripheral neuropathy, disease_protein with TTR, disease_protein with TTR. Definitions: CTS defined as following: Entrapment of the MEDIAN NERVE in the carpal tunnel, which is formed by the flexor retinaculum and the CARPAL BONES. This syndrome may be associated with repetitive occupational trauma (CUMULATIVE TRAUMA DISORDERS); wrist injuries; AMYLOID NEUROPATHIES; rheumatoid arthritis (see ARTHRITIS, RHEUMATOID); ACROMEGALY; PREGNANCY; and other conditions. Symptoms include burning pain and paresthesias involving the ventral surface of the hand and fingers which may radiate proximally. Impairment of sensation in the distribution of the median nerve and thenar muscle atrophy may occur. (Joynt, Clinical Neurology, 1995, Ch51, p45). malunion defined as following: Faulty healing of bone, resulting in improper anatomical alignment.. fracture defined as following: A traumatic injury to the bone in which the continuity of the bone is broken.. CRPS defined as following: Conditions characterized by pain involving an extremity or other body region, HYPERESTHESIA, and localized autonomic dysfunction following injury to soft tissue or nerve. The pain is usually associated with ERYTHEMA; SKIN TEMPERATURE changes, abnormal sudomotor activity (i.e., changes in sweating due to altered sympathetic innervation) or edema. The degree of pain and other manifestations is out of proportion to that expected from the inciting event. Two subtypes of this condition have been described: type I; (REFLEX SYMPATHETIC DYSTROPHY) and type II; (CAUSALGIA). (From Pain 1995 Oct;63(1):127-33). tendon defined as following: Fibrous bands or cords of CONNECTIVE TISSUE at the ends of SKELETAL MUSCLE FIBERS that serve to attach the MUSCLES to bones and other structures.. neuropathy defined as following: A disorder affecting the cranial nerves or the peripheral nervous system. It manifests with pain, tingling, numbness, and muscle weakness. It may be the result of physical injury, toxic substances, viral diseases, diabetes, renal failure, cancer, and drugs.. rupture defined as following: Forcible or traumatic tear or break of an organ or other soft part of the body..", "label": "yes"} {"id": "converted_3344", "sentence1": "Is marimastat effective for small-cell lung cancer?", "sentence2": "The phase III trial in small cell lung cancer was discontinued when the results of study 140 were released in February 2001 showing that marimastat was not significantly more effective than placebo in prolonging the survival of small cell lung cancer patients., CONCLUSION: Treatment with marimastat after induction therapy for SCLC did not result in improved survival and had a negative impact on quality of life., There were no significant differences in survival in a non-small cell lung cancer prinomastat study, and in a small cell lung cancer marimastat trial., There were no significant differences in survival in a non-small cell lung cancer prinomastat study , and in a small cell lung cancer marimastat trial. , The phase III trial in small cell lung cancer was discontinued when the results of study 140 were released in February 2001 showing that marimastat was not significantly more effective than placebo in prolonging the survival of small cell lung cancer patients.[SEP]Relations: Marimastat has relations: drug_protein with MMP20, drug_protein with MMP20, drug_protein with MMP7, drug_protein with MMP7, drug_protein with MMP10, drug_protein with MMP10. small cell lung carcinoma has relations: disease_disease with small cell carcinoma, disease_disease with small cell carcinoma, disease_disease with lung carcinoma, disease_disease with lung carcinoma. Definitions: SCLC defined as following: A form of highly malignant lung cancer that is composed of small ovoid cells (SMALL CELL CARCINOMA).. marimastat defined as following: An orally-active synthetic hydroxamate with potential antineoplastic activity. Marimastat covalently binds to the zinc(II) ion in the active site of matrix metalloproteinases (MMPs), thereby inhibiting the action of MMPs, inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis. This agent may also inhibit tumor necrosis factor-alpha converting enzyme (TACE), an enzyme involved in tumor necrosis factor alpha (TNF-alpha) production that may play a role in some malignancies as well as in the development of arthritis and sepsis. (NCI04).", "label": "no"} {"id": "converted_4210", "sentence1": "Is the zelda transcription factor a chromatin remodeller?", "sentence2": "ncreasing the number of Zelda binding sites accelerates the kinetics of nuclei transcriptional activation regardless of their transcriptional past, Zelda facilitates transcriptional activation by accumulating in microenvironments where it could accelerate the duration of multiple pre-initiation steps., Zelda acts through specific chromatin patterns of histone modifications to mark developmental enhancers and active promoters, Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation., The Drosophila genome activator Vielfaltig (Vfl), also known as Zelda (Zld), is thought to prime enhancers for activation by patterning transcription factors (TFs). Such priming is accompanied by increased chromatin accessibility, early enhancers are characterized by an intrinsically high nucleosome barrier. Zld tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of Zld motifs., Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo, Open chromatin is associated with Zelda-bound loci, as well as more generally with regions of active transcriptio, During this developmental transition, the zygotic genome is largely transcriptionally quiescent and undergoes significant chromatin remodeling. In Drosophila, the DNA-binding protein Zelda (also known as Vielfaltig) is required for this transition and for transcriptional activation of the zygotic genome., Zld facilitates binding of Dl to regulatory DNA, and that this is associated with increased chromatin accessibility., Importantly, the change in chromatin accessibility is strongly correlated with the change in Zld binding, Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo., We propose that both Zelda and GAGA factor function to specify sites of open chromatin and together facilitate the remodeling of the early embryonic genome., is analysis highlighted a strong and specific enrichment of predicted ZGA-associated CRMs for Zelda, CBP, Trl binding sites, as well as for histone marks associated with active enhancers (H3K4me1) and for open chromatin regions.CO, We demonstrate that Zelda is essential for hundreds of regions of open chromatin., Intriguingly, some Zelda sites still maintain these chromatin patterns in Drosophila embryos lacking maternal Zelda protein., Zelda potentiates morphogen activity by increasing chromatin accessibility., Zelda binds cis-regulatory elements (TAGteam heptamers), making chromatin accessible for gene transcription., zinc-finger TF zelda (zld) is essential for the maternal-to-zygotic transition (MZT) in Drosophila melanogaster, where it directly binds over thousand cis-regulatory modules to regulate chromatin accessibility. D. mela, This Zelda-mediated chromatin accessibility facilitates transcription-factor recruitment and early gene expression., While analyzing chromatin immunoprecipitation data sets from 21 sequence-specific transcription factors active in the Drosophila embryo, we found that binding of all factors exhibits a dose-dependent relationship with \"TAGteam\" sequence motifs bound by the zinc finger protein Vielfaltig, also known as Zelda, a recently discovered activator of the zygotic genome., These different timing classes each associate with binding sites for two transcription factors, GAGA-factor and Zelda, previously implicated in controlling chromatin accessibility at ZGA., Together this reveals a distinct requirement for a chromatin remodeller in promoting the activity of the pioneer factor OCT4 and regulating the pluripotency network., Chromatin accessibility at OCT4-bound sites requires the chromatin remodeller BRG1, which is recruited to these sites by OCT4 to support additional transcription factor binding and expression of the pluripotency-associated transcriptome., The pioneer factor OCT4 requires the chromatin remodeller BRG1 to support gene regulatory element function in mouse embryonic stem cells., Pioneer transcription factors recognise and bind their target sequences in inaccessible chromatin to establish new transcriptional networks throughout development and cellular reprogramming., During this process, pioneer factors establish an accessible chromatin state to facilitate additional transcription factor binding, yet it remains unclear how different pioneer factors achieve this., Here, we discover that the pluripotency-associated pioneer factor OCT4 binds chromatin to shape accessibility, transcription factor co-binding, and regulatory element function in mouse embryonic stem cells., Open chromatin is associated with Zelda-bound loci, as well as more generally with regions of active transcription., Unexpectedly, chromatin at a large subset of Zelda-bound regions remains open even in the absence of Zelda., During this developmental transition, the zygotic genome is largely transcriptionally quiescent and undergoes significant chromatin remodeling., Here we used formaldehyde-assisted isolation of regulatory elements to determine the role of Zelda in regulating regions of open chromatin in the early embryo., Pioneer transcription factors can engage nucleosomal DNA, which leads to local chromatin remodeling and to the establishment of transcriptional competence., Recently, we showed that Zelda acts through specific chromatin patterns of histone modifications to mark developmental enhancers and active promoters., The zinc-finger TF zelda (zld) is essential for the maternal-to-zygotic transition (MZT) in Drosophila melanogaster, where it directly binds over thousand cis-regulatory modules to regulate chromatin accessibility., Nonetheless, the extent to which Zelda influences chromatin accessibility across the genome is largely unknown., We present evidence that Zld facilitates binding of Dl to regulatory DNA, and that this is associated with increased chromatin accessibility., ZRF1 facilitates the remodeling of multiprotein complexes at chromatin and lies at the heart of signaling processes that occur at DNA damage sites and during transcriptional activation., We postulate that ZRF1 operates in conjunction with cellular remodeling machines and suggest that on-site remodeling might be a hallmark of many chromatin-associated signaling pathways., Reconstituted transcription reactions established that the Brahma (BRM) chromatin-remodeling complex is essential for Zeste-directed activation on nucleosomal templates.[SEP]Relations: transcription factor binding has relations: molfunc_protein with RARA, molfunc_protein with RARA, molfunc_protein with ZFPM2, molfunc_protein with ZFPM2, molfunc_protein with RORA, molfunc_protein with RORA, molfunc_protein with CENPF, molfunc_protein with CENPF, molfunc_protein with RNF19A, molfunc_protein with RNF19A. Definitions: nucleosomes defined as following: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4.. OCT4 defined as following: This gene plays a role in early mammalian development.. histone modifications defined as following: The covalent alteration of one or more amino acid residues within a histone protein. [GOC:krc]. genome defined as following: Anatomical set of genes in all the chromosomes.. binding sites defined as following: The parts of a macromolecule that directly participate in its specific combination with another molecule.. multiprotein complexes defined as following: Macromolecular complexes formed from the association of defined protein subunits.. transcription factor defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. Brahma defined as following: The Drosophila gene brahma (brm) encodes a non-specific RNA polymerase II transcription co-activator, assisting one or more transcriptional activators of ANT-C and BX-C homeotic genes. Brm can counteract the repressive effect of polycomb protein and exhibits DNA-dependent ATPase activity. It contains a SNF2 related domain, a DEAD/DEAH box helicase, a helicase C-terminal domain, and belongs to the SNF2/RAD54 helicase family. Two isoforms (long and short) may be produced by alternative splicing. Highest expression is seen in unfertilized eggs and early embryos. It interacts genetically with Antp, trx, Psc, Pc, hh, and several other genes. Similar sequences have been identified in Caenorhabditis elegans, Gallus gallus, Homo sapiens, Mus musculus, and Saccharomyces cerevisiae. (from SWISS-PROT P25439, FlyBase 0000212, and NCI). chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. position defined as following: A reference to the alignment of an object, a particular situation or view of a situation, or the location of an object.. H3K4me1 defined as following: A form of histone H3 where the lysine residue at position 4 has been post-translationally modified with a single methyl group. This modification may be a marker for transcriptionally active genes.. regulatory element defined as following: Nucleic acid sequences involved in regulating the expression of genes.. mouse embryonic stem cells defined as following: PLURIPOTENT STEM CELLS derived from the BLASTOCYST INNER CELL MASS of day 3.5 mouse embryos.. sites defined as following: A position in relation to its surroundings.. BRG1 defined as following: Human SMARCA4 wild-type allele is located in the vicinity of 19p13.3 and is approximately 101 kb in length. This allele, which encodes probable global transcription activator SNF2L4 protein, plays a role in both transcriptional progression and chromatin structural modulation.. CO defined as following: This gene plays a role in transmembrane transport of water..", "label": "yes"} {"id": "converted_1615", "sentence1": "Are high-flow nasal cannulae effective for treatment of preterm infants?", "sentence2": "The use of high-flow nasal cannulae is an increasingly popular alternative to nasal continuous positive airway pressure (CPAP) for noninvasive respiratory support of very preterm infants (gestational age, <32 weeks) after extubation., The use of high-flow nasal cannulae was noninferior to the use of nasal CPAP, with treatment failure occurring in 52 of 152 infants (34.2%) in the nasal-cannulae group and in 39 of 151 infants (25.8%) in the CPAP group (risk difference, 8.4 percentage points; 95% confidence interval, -1.9 to 18.7). , Although the result for the primary outcome was close to the margin of noninferiority, the efficacy of high-flow nasal cannulae was similar to that of CPAP as respiratory support for very preterm infants after extubation. , Recently high flow nasal cannula (HFNC) is emerging as an efficient, better tolerated form of NIV, allowing better access to the baby's face, which may improve nursing, feeding and bonding., In conclusion, there is a growing evidence of the feasibility of HFNC as an alternative mode of NIV. , HHHFNC and NCPAP produced similar rates of extubation failure., The use of HFNC as a respiratory support modality is increasing in the infant, pediatric, and adult populations as an alternative to non-invasive positive pressure ventilation., Current evidence suggests that HFNC is well tolerated and may be feasible in a subset of patients who require ventilatory support with non-invasive ventilation., Heated, humidified, high-flow nasal cannula oxygen therapy (HHHFNC) has been used to improve ventilation in preterm infants. , Increasing flow rates of HHHFNC therapy are associated with linear increases in NP pressures in bronchiolitis patients. , An alternative to the use of nasal continuous positive airway pressure (NCPAP) as a non-invasive modality to support respiratory distress in premature infants has been the recent introduction of high flow nasal cannula (HFNC) devices in many neonatal units. There has been increased use of HFNC presumably because of anecdotal reports and experience that it is easy to use, and well tolerated by the infants, while experiencing decreased nasal septumerosion., High-flow nasal cannulae (HFNC) are gaining in popularity as a form of non-invasive respiratory support for preterm infants in neonatal intensive care units around the world., HFNC may be as effective as NCPAP at improving respiratory parameters such as tidal volume and work of breathing in preterm infants, but probably only at flow rates >2 litres/min. , There is growing evidence of the feasibility of HFNC as an alternative to other forms of non-invasive ventilation in preterm infants. , When used as primary respiratory support after birth, one trial found similar rates of treatment failure in infants treated with HFNC and nasal CPAP. Following extubation, one trial found that infants treated with HFNC had a significantly higher rate of reintubation than those treated with nasal CPAP. Another trial found similar rates of reintubation for humidified and non-humidified HFNC, and the fourth trial found no difference between two different models of equipment used to deliver humidified HFNC. , When used following extubation, HFNC may be associated with a higher rate of reintubation than nasal CPAP. , Early weaning from CPAP to high flow nasal cannula in preterm infants is associated with prolonged oxygen requirement: a randomized controlled trial., After randomization, the no-NC group had fewer days on oxygen [median (interquartile range): 5 (1-8) vs 14 (7.5-19.25) days, p<0.001] and shorter duration of respiratory support [10.5 (4-21) vs 18 (11.5-29) days, p=0.03]. There were no differences between groups regarding success of weaning from NCPAP. , Weaning preterm infants from NCPAP to NC is associated with increased exposure to oxygen and longer duration of respiratory support., A number of centers use high-flow nasal cannula (HFNC) in the management of AOP without measuring the positive distending pressure (PDP) generated., HFNC is as effective as NCPAP in the management of AOP.[SEP]Relations: Respiratory distress has relations: drug_effect with Midazolam, drug_effect with Midazolam, drug_effect with Mometasone, drug_effect with Mometasone, drug_effect with Nelarabine, drug_effect with Nelarabine, drug_effect with Triazolam, drug_effect with Triazolam. Bronchitis has relations: drug_effect with Mometasone, drug_effect with Mometasone. Definitions: NIV defined as following: A type of mechanical ventilation procedure that uses a non-invasive means, such as a face mask or nasal mask, to deliver oxygenated air into the lungs.. respiratory distress defined as following: A pathological increase in the effort and frequency of breathing movements.. NC defined as following: A rare developmental skin condition consisting of abnormal pilosebaceous follicle development. It is characterized by linear or band-like distributions of groups of comedones, usually on the face, neck, upper arm, chest, and abdomen, that appear at birth or in childhood.. bronchiolitis defined as following: Inflammation of the BRONCHIOLES..", "label": "yes"} {"id": "converted_2509", "sentence1": "Is creatinine assessment included in the MELD score?", "sentence2": "Model For End-Stage Liver Disease (MELD) scores were calculated as 3.78×ln[TB] + 11.2×ln[INR] + 9.57×ln[creatinine] + 6.43. , A corrected creatinine was derived from the mGFR after application of the Modification of Diet in Renal Disease formula. Subsequently, a corrected MELD was calculated and compared with the conventionally calculated MELD., Among patients with MELD score>35, a new prognostic model based on serum creatinine, need for hemodialysis and moderate ascites could identify the sickest one., Patient risk factors evaluated include age, INR (international normalized ratio), creatinine, bilirubin, and MELD score (Model for End-of-stage Liver Disease). , Limited comparability of creatinine assays in patients with liver cirrhosis and their impact on the MELD score., The model of end-stage liver disease (MELD) score is used for this purpose in most countries and incorporates bilirubin, International Normalized ratio, and creatinine. , The MELD score was calculated using international normalized ratio, serum billirubin and creatinine., Regression analysis identified high creatinine and INR, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. , This study aimed to evaluate the impact of two creatinine measurement methods on the Model for End Stage Liver Disease (MELD) score and glomerular filtration rate estimation (eGFR) in cirrhotic patients., OBJECTIVES: The model for end-stage liver disease score (MELD = 3.8*LN[total bilirubin] + 9.6*LN[creatinine] + 11.2*[PT-INR] + 6.4) predicts mortality for tricuspid valve surgery., Simplified MELD score = 3.8*LN[total bilirubin] + 9.6*LN[creatinine] + 6.4.Respond with exceptions, completions and modifications or revisions done before completion
. liver cirrhosis defined as following: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules..", "label": "yes"} {"id": "converted_811", "sentence1": "Is myasthenia gravis associated with osteoporosis?", "sentence2": "We performed PVP in 4 patients with generalized MG associated with recent steroid-induced symptomatic VFs. , In this case report, we used tacrolimus to successfully treat a 13-year-old boy with ocular MG who had suffered from severe steroid complications, including a failure of thrive and osteoporosis., INTRODUCTION: Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk. , RESULTS: Compared to the control cohort, there was no statistically significant increased risk observed in patients with MG for any fracture (adjusted hazard ratio [AHR] 1.11; 95 % confidence interval [CI], 0.84-1.47) or osteoporotic fractures (AHR 0.98 [95 % CI 0.67-1.41]). Further, use of oral glucocorticoids up to a cumulative dose exceeding 5 g prednisolone equivalents did not increase risk of osteoporotic fracture (AHR 0.99 [95 % CI, 0.31-3.14]) compared with MG patients without glucocorticoid exposure., The RANKL/OPG ratio and indices of bone metabolisms are also not affected by THX, although THX increases the levels of IL-7 and RANKL., Both disorders had been controlled for around 15 years by oral prednisolone and a cholinesterase inhibitor following surgical removal of invasive thymoma and radiotherapy, but muscular weakness due to myalgia and an increase in serum levels of myogenic enzymes, mainly ascribable to the recurrence of PM, reappeared immediately after cessation of these drugs, which was done because the patient had multiple bone fractures and severe osteoporosis due to the long-term corticosteroid therapy. , We measured bone density in 36 patients (26 females and 10 males) who had undergone long-term prednisolone administration, and found a decrease in bone density in 31% of female patients and osteoporosis in only 11.5% (three cases)., In conclusion, prednisolone-treated patients with myasthenia gravis have an acceptable risk of bone loss if prophylactic medication is administered., INTRODUCTION: Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk., Alendronate should be used with caution in patients with myasthenia gravis who have corticosteroid-induced osteoporosis, In this paper we present two cases of young women who developed severe PAO with vertebral fractures: a 42-year-old woman with a family history of osteoporosis, and a 21-year-old woman affected with myasthenia gravis, Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk[SEP]Relations: myasthenia gravis has relations: disease_phenotype_positive with Acrocyanosis, disease_phenotype_positive with Acrocyanosis, disease_phenotype_positive with Myositis, disease_phenotype_positive with Myositis, disease_protein with FAS, disease_protein with FAS, disease_phenotype_positive with Rheumatoid arthritis, disease_phenotype_positive with Rheumatoid arthritis, disease_protein with MUSK, disease_protein with MUSK. Definitions: RANKL defined as following: Human TNFSF11 wild-type allele is located within 13q14 and is approximately 45 kb in length. This allele, which encodes tumor necrosis factor ligand superfamily member 11 protein, plays a role in osteoclast differentiation and activation. This allele also is involved in apoptotic signal transduction and regulation.. osteoporotic fracture defined as following: A pathologic bone fracture due to osteoporosis. It is generally caused by a fall from a standing height or lower and usually involves the spine, hip, or wrist.. fracture defined as following: A traumatic injury to the bone in which the continuity of the bone is broken.. MG defined as following: A disorder of neuromuscular transmission characterized by fatigable weakness of cranial and skeletal muscles with elevated titers of ACETYLCHOLINE RECEPTORS or muscle-specific receptor tyrosine kinase (MuSK) autoantibodies. Clinical manifestations may include ocular muscle weakness (fluctuating, asymmetric, external ophthalmoplegia; diplopia; ptosis; and weakness of eye closure) and extraocular fatigable weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles (ocular myasthenia). THYMOMA is commonly associated with this condition.. neuromuscular disease defined as following: A general term encompassing lower MOTOR NEURON DISEASE; PERIPHERAL NERVOUS SYSTEM DISEASES; and certain MUSCULAR DISEASES. Manifestations include MUSCLE WEAKNESS; FASCICULATION; muscle ATROPHY; SPASM; MYOKYMIA; MUSCLE HYPERTONIA, myalgias, and MUSCLE HYPOTONIA.. steroid defined as following: A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed). vertebral fractures defined as following: Broken bones in the vertebral column.. Alendronate defined as following: A nonhormonal medication for the treatment of postmenopausal osteoporosis in women. This drug builds healthy bone, restoring some of the bone loss as a result of osteoporosis.. myalgia defined as following: Painful sensation in the muscles.. bone loss defined as following: Decreased calcification or density of bone tissue.. IL-7 defined as following: A recombinant protein which is chemically identical to or similar to endogenous interleukin-7 (IL-7) with hematopoietic and immunopotentiating properties. Produced by bone marrow, thymic stromal, and spleen cells, the cytokine interleukin-7 is a hematopoietic growth factor for progenitor B cells and T cells and stimulates proliferation and differentiation of mature T-cells and Natural Killer cells. (NCI05). muscular weakness defined as following: A vague complaint of debility, fatigue, or exhaustion attributable to weakness of various muscles. The weakness can be characterized as subacute or chronic, often progressive, and is a manifestation of many muscle and neuromuscular diseases. (From Wyngaarden et al., Cecil Textbook of Medicine, 19th ed, p2251). AHR defined as following: approximately 280kD soluble protein complex; binds and mediates carcinogenesis by polycyclic aromatic hydrocarbons, heterocyclic amines, and chlorinated aromatic compounds.. prednisolone defined as following: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.. myasthenia gravis defined as following: A disorder of neuromuscular transmission characterized by fatigable weakness of cranial and skeletal muscles with elevated titers of ACETYLCHOLINE RECEPTORS or muscle-specific receptor tyrosine kinase (MuSK) autoantibodies. Clinical manifestations may include ocular muscle weakness (fluctuating, asymmetric, external ophthalmoplegia; diplopia; ptosis; and weakness of eye closure) and extraocular fatigable weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles (ocular myasthenia). THYMOMA is commonly associated with this condition..", "label": "yes"} {"id": "converted_281", "sentence1": "Are reduced-nicotine cigarettes effective for smoking cessation?", "sentence2": "CONCLUSIONS: In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. , RESULTS: Significant reductions in nicotine intake were observed between usual brand smoking (∼1.2 mg nicotine) and the 0.3 and 0.05 mg nicotine emission cigarettes, but not the 0.6 mg cigarette., CONCLUSIONS: The study adds to the evidence that cigarettes with markedly reduced nicotine content are not associated with increased smoking intensity or exposure to smoke toxicants., BACKGROUND: When switching from usual brand cigarettes, very low nicotine content (VLNC) cigarettes lead to a reduction in the number of cigarettes smoked, toxicant exposure, withdrawal symptoms and dependence. , Moreover, while nicotine patches were well tolerated when subjects smoked nicotine-containing cigarettes, the use of nicotine skin patches with reduced-nicotine cigarettes potentially offers the advantage of increased efficacy without introducing concern about toxic effects of excessive nicotine intake., Results showed that Quest plus NRT was more effective than active control plus NRT in achieving 4 weeks of continuous abstinence (32.8% vs. 21.9%)., Quest plus NRT offers promise as a new smoking cessation treatment., We identified three clinical trials (total n = 489) that suggest that smokers can dissociate nicotine delivery from the act of smoking if they use reduced-nicotine content cigarettes in combination with nicotine replacement therapy., CONCLUSION: The 0.05 mg nicotine yield cigarettes may be a tobacco product that can facilitate cessation; however, future research is clearly needed to support these preliminary findings., Preliminary studies suggest an extinction-based smoking cessation treatment using reduced nicotine content (RNC) cigarettes decreases self-report craving for cigarettes prior to quitting and may be an effective smoking cessation treatment., Reduced nicotine content (RNC) cigarettes have led to smoking fewer cigarettes, withdrawal relief, and facilitation of cessation., Evidence from a number of small smoking cessation studies suggests that the use of cigarettes with reduced nicotine content, in combination with nicotine replacement therapy (NRT), may help reduce withdrawal symptoms and increase quit rates., The concept for a reduced-nicotine cigarette designed to progressively wean smokers from the smoking habit is based on research demonstrating that successful smoking cessation is not only dependent on withdrawal of nicotine, but also on weaning from the habitual sensory and behavioral reinforcement of smoking., Preliminary studies suggest an extinction-based smoking cessation treatment using reduced nicotine content (RNC) cigarettes decreases self-report craving for cigarettes prior to quitting and may be an effective smoking cessation treatment, Specifically, standards that required substantially reduced nicotine content in cigarettes could enable cessation in smokers and prevent future smoking among current non-smokers, Reduced nicotine content (RNC) cigarettes have led to smoking fewer cigarettes, withdrawal relief, and facilitation of cessation, Evidence from a number of small smoking cessation studies suggests that the use of cigarettes with reduced nicotine content, in combination with nicotine replacement therapy (NRT), may help reduce withdrawal symptoms and increase quit rates, The concept for a reduced-nicotine cigarette designed to progressively wean smokers from the smoking habit is based on research demonstrating that successful smoking cessation is not only dependent on withdrawal of nicotine, but also on weaning from the habitual sensory and behavioral reinforcement of smoking, These results suggest that use of NRT before a target quit-smoking date deserves further evaluation as a possible smoking cessation treatment. Moreover, while nicotine patches were well tolerated when subjects smoked nicotine-containing cigarettes, the use of nicotine skin patches with reduced-nicotine cigarettes potentially offers the advantage of increased efficacy without introducing concern about toxic effects of excessive nicotine intake., Preliminary studies suggest an extinction-based smoking cessation treatment using reduced nicotine content (RNC) cigarettes decreases self-report craving for cigarettes prior to quitting and may be an effective smoking cessation treatment.[SEP]Relations: Nicotine has relations: drug_effect with Cough, drug_effect with Cough, drug_effect with Arthritis, drug_effect with Arthritis, drug_effect with Respiratory failure, drug_effect with Respiratory failure, drug_drug with Cenobamate, drug_drug with Cenobamate, drug_effect with Headache, drug_effect with Headache. Definitions: nicotine defined as following: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.. smoke defined as following: Smoke from burning tobacco (cigarettes, cigars, or pipes) and exhaled by a smoker. Tobacco smoke contains nicotine, a stimulant, and other biologically active chemicals having carcinogenic properties.. NRT defined as following: Therapy to help control nicotine withdrawal symptoms during tobacco cessation.", "label": "yes"} {"id": "converted_2783", "sentence1": "Can pets affect infant microbiomed?", "sentence2": "Since there is some evidence that pets also alter the gut microbial composition of infants, changes to the gut microbiome are putative pathways by which pet exposure can reduce these risks to health., The impact of pet ownership varies under different birth scenarios; however, in common, exposure to pets increased the abundance of two bacteria, Ruminococcus and Oscillospira, which have been negatively associated with childhood atopy and obesity., As a common effect in all birth scenarios, pre- and postnatal pet exposure enriched the abundance of Oscillospira and/or Ruminococcus (P < 0.05) with more than a twofold greater likelihood of high abundance. Among vaginally born infants with maternal intrapartum antibiotic prophylaxis exposure, Streptococcaceae were substantially and significantly reduced by pet exposure (P < 0.001, FDRp = 0.03), reflecting an 80% decreased likelihood of high abundance (OR 0.20, 95%CI, 0.06-0.70) for pet exposure during pregnancy alone and a 69% reduced likelihood (OR 0.31, 95%CI, 0.16-0.58) for exposure in the pre- and postnatal time periods., Exposure to household furry pets influences the gut microbiota of infant at 3-4 months following various birth scenarios.[SEP]Relations: Bacteremia has relations: disease_phenotype_positive with listeriosis, disease_phenotype_positive with listeriosis, disease_phenotype_positive with toxic shock syndrome, disease_phenotype_positive with toxic shock syndrome, disease_phenotype_positive with shigellosis, disease_phenotype_positive with shigellosis, disease_phenotype_positive with cyclic hematopoiesis, disease_phenotype_positive with cyclic hematopoiesis. obsolete body mass index quantitative trait locus 19 has relations: disease_phenotype_positive with Insulin resistance, disease_phenotype_positive with Insulin resistance. Definitions: atopy defined as following: Human MS4A2 wild-type allele is located within 11q12-q13 and is approximately 10 kb in length. This allele, which encodes high affinity immunoglobulin epsilon receptor subunit beta protein, plays a role in both immunoglobulin binding and mast cell responses.. pet defined as following: An imaging technique using compounds labelled with short-lived positron-emitting radionuclides (such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18) to measure cell metabolism. It has been useful in study of soft tissues such as CANCER; CARDIOVASCULAR SYSTEM; and brain. SINGLE-PHOTON EMISSION-COMPUTED TOMOGRAPHY is closely related to positron emission tomography, but uses isotopes with longer half-lives and resolution is lower.. bacteria defined as following: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive..", "label": "yes"} {"id": "converted_2559", "sentence1": "Are there ways of joint Bayesian inference of risk variants?", "sentence2": "Joint Bayesian inference of risk variants and tissue-specific epigenomic enrichments across multiple complex human diseases., Genome wide association studies (GWAS) provide a powerful approach for uncovering disease-associated variants in human, but fine-mapping the causal variants remains a challenge. This is partly remedied by prioritization of disease-associated variants that overlap GWAS-enriched epigenomic annotations. Here, we introduce a new Bayesian model RiVIERA (Risk Variant Inference using Epigenomic Reference Annotations) for inference of driver variants from summary statistics across multiple traits using hundreds of epigenomic annotations. In simulation, RiVIERA promising power in detecting causal variants and causal annotations, the multi-trait joint inference further improved the detection power. We applied RiVIERA to model the existing GWAS summary statistics of 9 autoimmune diseases and Schizophrenia by jointly harnessing the potential causal enrichments among 848 tissue-specific epigenomics annotations from ENCODE/Roadmap consortium covering 127 cell/tissue types and 8 major epigenomic marks. RiVIERA identified meaningful tissue-specific enrichments for enhancer regions defined by H3K4me1 and H3K27ac for Blood T-Cell specifically in the nine autoimmune diseases and Brain-specific enhancer activities exclusively in Schizophrenia. Moreover, the variants from the 95% credible sets exhibited high conservation and enrichments for GTEx whole-blood eQTLs located within transcription-factor-binding-sites and DNA-hypersensitive-sites., Here, we introduce a new Bayesian model RiVIERA (Risk Variant Inference using Epigenomic Reference Annotations) for inference of driver variants from summary statistics across multiple traits using hundreds of epigenomic annotations., Joint Bayesian inference of risk variants and tissue-specific epigenomic enrichments across multiple complex human diseases.[SEP]Relations: autoimmune disease has relations: disease_disease with euthyroid Graves orbitopathy, disease_disease with euthyroid Graves orbitopathy, disease_disease with vitiligo-associated multiple autoimmune disease susceptibility 1, disease_disease with vitiligo-associated multiple autoimmune disease susceptibility 1. gene expression has relations: bioprocess_protein with IKBKE, bioprocess_protein with IKBKE. schizophreniform disorder has relations: contraindication with Betamethasone, contraindication with Betamethasone, contraindication with Hydrocortisone, contraindication with Hydrocortisone. Definitions: variants defined as following: An alteration or difference from a norm or standard.. conservation defined as following: The maintenance of certain characteristics in an unchanged condition.. human defined as following: Members of the species Homo sapiens.. autoimmune diseases defined as following: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.. H3K4me1 defined as following: A form of histone H3 where the lysine residue at position 4 has been post-translationally modified with a single methyl group. This modification may be a marker for transcriptionally active genes.. GTEx defined as following: A program sponsored by the National Institutes of Health's Common Fund, designed to provide insights into the mechanisms of gene regulation by studying human gene expression and regulation in multiple tissues from healthy individuals, exploring disease-related perturbations in a variety of human diseases, and examining sexual dimorphisms in gene expression and regulation in multiple tissues. Genetic variation between individuals will be examined for correlation with differences in gene expression level to identify regions of the genome that influence whether and how much a gene is expressed..", "label": "yes"} {"id": "converted_1325", "sentence1": "Do all archaea possess multiple origins of DNA replication?", "sentence2": "Origins differ in number and structure across the three domains of life and their properties determine the dynamics of chromosome replication. Bacteria and some archaea replicate from single origins, whereas most archaea and all eukaryotes replicate using multiple origins., Replication starts at a single Ori site in bacteria, but in eukaryotes multiple Ori sites are used for fast copying across all chromosomes. The situation becomes complex in archaea, where some groups have single and others have multiple origins of replication., Results from this in silico analysis show that the Themococcales have a single origin of replication., Until recently, the only archaeon for which a bona fide origin of replication was reported was Pyrococcus abyssi, where a single origin was identified. Although several in silico analyses have suggested that some archaeal species might contain more than one origin, this has only been demonstrated recently., In bacteria and eukaryotes, replication initiates from single and multiple origins, respectively, while archaea can adopt either of the two modes., Bacteria and some archaea replicate from single origins, whereas most archaea and all eukaryotes replicate using multiple origins., Bacteria and some archaea replicate from single origins, whereas most archaea and all eukaryotes replicate using multiple origins[SEP]Relations: Bacteremia has relations: disease_phenotype_positive with cyclic hematopoiesis, disease_phenotype_positive with cyclic hematopoiesis, disease_phenotype_positive with melioidosis, disease_phenotype_positive with melioidosis, disease_phenotype_positive with listeriosis, disease_phenotype_positive with listeriosis, disease_phenotype_positive with nocardiosis, disease_phenotype_positive with nocardiosis, disease_phenotype_positive with shigellosis, disease_phenotype_positive with shigellosis. Definitions: archaea defined as following: One of the three domains of life (the others being BACTERIA and Eukarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: (1) the presence of characteristic tRNAs and ribosomal RNAs; (2) the absence of peptidoglycan cell walls; (3) the presence of ether-linked lipids built from branched-chain subunits; and (4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least four kingdoms: CRENARCHAEOTA; EURYARCHAEOTA; NANOARCHAEOTA; and KORARCHAEOTA.. eukaryotes defined as following: Organism or cells with a nucleus separated from the cytoplasm by a two membrance nuclear envelope and compartmentalization of function into distinct cytoplasmic organelles.. Bacteria defined as following: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.. chromosomes defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification..", "label": "no"} {"id": "converted_933", "sentence1": "Are patients with marfan syndrome at increased risk of arrhythmias?", "sentence2": "Marfan syndrome (MFS) is a variable, autosomal-dominant disorder of the connective tissue. In MFS serious ventricular arrhythmias and sudden cardiac death (SCD) can occur., Marfan's patients carry increased risk for cardiac arrhythmias. , Ventricular arrhythmias were present in 21% and were associated with increased left ventricular size, mitral valve prolapse, and abnormalities of repolarization., Cardiac complications are rare in young patients with Marfan syndrome receiving medical therapy and close clinical follow-up. Sudden death still occurs, and appears more common in patients with a dilated left ventricle. Left ventricular dilation may predispose to alterations of repolarization and fatal ventricular arrhythmias.[SEP]Relations: Marfan syndrome has relations: disease_disease with Marfan and Marfan-related disorder, disease_disease with Marfan and Marfan-related disorder, disease_phenotype_positive with Chronic fatigue, disease_phenotype_positive with Chronic fatigue, disease_protein with CAT, disease_protein with CAT, disease_protein with NODAL, disease_protein with NODAL, disease_phenotype_positive with Arthralgia/arthritis, disease_phenotype_positive with Arthralgia/arthritis. Definitions: mitral valve prolapse defined as following: Abnormal protrusion or billowing of one or both of the leaflets of MITRAL VALVE into the LEFT ATRIUM during SYSTOLE. This allows the backflow of blood into left atrium leading to MITRAL VALVE INSUFFICIENCY; SYSTOLIC MURMURS; or CARDIAC ARRHYTHMIA.. MFS defined as following: An autosomal dominant disorder of CONNECTIVE TISSUE with abnormal features in the heart, the eye, and the skeleton. Cardiovascular manifestations include MITRAL VALVE PROLAPSE; AORTIC ANEURYSM; and AORTIC DISSECTION. Other features include lens displacement (ectopia lentis), disproportioned long limbs and enlarged DURA MATER (dural ectasia). Marfan syndrome (type 1) is associated with mutations in the gene encoding FIBRILLIN-1 (FBN1), a major element of extracellular microfibrils of connective tissue. Mutations in the gene encoding TYPE II TGF-BETA RECEPTOR (TGFBR2) are associated with Marfan syndrome type 2.. Cardiac complications defined as following: Any heart or vascular disorder occurring as a consequence of injury to the cardiovascular system.. Marfan syndrome defined as following: This gene is involved in the maintenance of connective tissue.. ventricular arrhythmias defined as following: A disorder characterized by an electrocardiographic finding of an atypical cardiac rhythm resulting from a pathologic process in the cardiac ventricles.. Sudden death defined as following: The abrupt cessation of all vital bodily functions, manifested by the permanent loss of total cerebral, respiratory, and cardiovascular functions.. connective tissue defined as following: Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX.. sudden cardiac death defined as following: Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005). marfan syndrome defined as following: An autosomal dominant disorder of CONNECTIVE TISSUE with abnormal features in the heart, the eye, and the skeleton. Cardiovascular manifestations include MITRAL VALVE PROLAPSE; AORTIC ANEURYSM; and AORTIC DISSECTION. Other features include lens displacement (ectopia lentis), disproportioned long limbs and enlarged DURA MATER (dural ectasia). Marfan syndrome (type 1) is associated with mutations in the gene encoding FIBRILLIN-1 (FBN1), a major element of extracellular microfibrils of connective tissue. Mutations in the gene encoding TYPE II TGF-BETA RECEPTOR (TGFBR2) are associated with Marfan syndrome type 2.. arrhythmias defined as following: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction..", "label": "yes"} {"id": "converted_2565", "sentence1": "Does armodafinil improve fatigue of glioma patients?", "sentence2": "CONCLUSIONS: While treatment was well-tolerated, an 8-week course of armodafinil did not improve fatigue or QOL in glioma patients undergoing RT in this pilot study. , We evaluated whether armodafinil, a wakefulness-promoting medication, improves fatigue in glioma patients undergoing RT., Armodafinil did not significantly improve fatigue or QOL based on the 42-day change in FACIT-F fatigue subscale, FACT-G, CFS, or BFI. Further analysis suggests no difference between the arms even after accounting for the potential bias of missing data. , Treatment was well tolerated with few grade 3 or 4 toxicities.Target person is partially aware of the issue.
. antigen defined as following: Substances that are recognized by the immune system and induce an immune reaction.. fludarabine defined as following: A fluorinated nucleotide antimetabolite analog of the antiviral agent vidarabine (ara-A) with antineoplastic activity. Administered parenterally as a phosphate salt, fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite may inhibit DNA polymerase alpha, ribonucleotide reductase and DNA primase, thereby interrupting DNA synthesis and inhibiting tumor cell growth. (NCI04). mitoxantrone defined as following: An anthracenedione-derived antineoplastic agent.. Kaposi sarcoma defined as following: A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Kaposi's sarcoma occurs spontaneously in Jewish and Italian males in Europe and the United States. An aggressive variant in young children is endemic in some areas of Africa. A third form occurs in about 0.04% of kidney transplant patients. There is also a high incidence in AIDS patients. (From Dorland, 27th ed & Holland et al., Cancer Medicine, 3d ed, pp2105-7) HHV-8 is the suspected cause.. PR defined as following: Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives.. CD52 antigen defined as following: A small GPI-linked glycoprotein expressed on the surface of normal and malignant B-CELLS; T-CELLS; MONOCYTES; MACROPHAGES; NK CELLS; and GRANULOCYTES. It is expressed densely and without modulation in many malignant T-cell neoplasms and therefore a target for antibody therapies (e.g., ALEMTUZUMAB).. B-cell chronic lymphocytic leukemia defined as following: A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.. ALL defined as following: Leukemia with an acute onset, characterized by the presence of lymphoblasts in the bone marrow and the peripheral blood. It includes the acute B lymphoblastic leukemia and acute T lymphoblastic leukemia.. human defined as following: Members of the species Homo sapiens.. hematological malignancies defined as following: Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.. alemtuzumab defined as following: Any monoclonal antibody directed against the cell surface glycoprotein CD52, regardless of the antibody type (e.g., rat, mouse, humanized)..", "label": "yes"} {"id": "converted_2588", "sentence1": "Are osteoclasts specialized in bone degradation?", "sentence2": "osteoclast-mediated attack on bone, Bone degradation is caused by osteoclasts, the normal bone-resorbing cells. , Cathepsin K is a highly potent collagenase in osteoclasts and is responsible for bone degradation., In osteoclasts, Src controls podosome organization and bone degradation, which leads to an osteopetrotic phenotype in src(-/-) mice, Bone degradation by osteoclasts depends on the formation of a sealing zone, composed of an interlinked network of podosomes, which delimits the degradation lacuna into which osteoclasts secrete acid and proteolytic enzymes. [SEP]Relations: osteoclast fusion has relations: bioprocess_protein with CD81, bioprocess_protein with CD81, bioprocess_protein with SBNO2, bioprocess_protein with SBNO2, bioprocess_protein with CD109, bioprocess_protein with CD109, bioprocess_protein with SH3PXD2A, bioprocess_protein with SH3PXD2A, bioprocess_protein with TCTA, bioprocess_protein with TCTA. Definitions: acid defined as following: Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. (Grant & Hackh's Chemical Dictionary, 5th ed). osteoclasts defined as following: A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.. Src defined as following: Proto-oncogene tyrosine-protein kinase Src (536 aa, ~60 kDa) is encoded by the human SRC gene. This protein is involved in both receptor-mediated signal transduction and tyrosine phosphorylation.. collagenase defined as following: A metalloproteinase which degrades helical regions of native collagen to small fragments. Preferred cleavage is -Gly in the sequence -Pro-Xaa-Gly-Pro-. Six forms (or 2 classes) have been isolated from Clostridium histolyticum that are immunologically cross-reactive but possess different sequences and different specificities. Other variants have been isolated from Bacillus cereus, Empedobacter collagenolyticum, Pseudomonas marinoglutinosa, and species of Vibrio and Streptomyces. EC 3.4.24.3.. Cathepsin K defined as following: A cysteine protease that is highly expressed in OSTEOCLASTS and plays an essential role in BONE RESORPTION as a potent EXTRACELLULAR MATRIX-degrading enzyme.. podosomes defined as following: An actin-rich adhesion structure characterized by formation upon cell substrate contact and localization at the substrate-attached part of the cell, contain an F-actin-rich core surrounded by a ring structure containing proteins such as vinculin and talin, and have a diameter of 0.5 mm. [PMID:12837608, PMID:15890982].", "label": "yes"} {"id": "converted_4279", "sentence1": "Are variants in FHF2 (also known as FGF13) associated with encephalopathy?", "sentence2": "Missense variants in the N-terminal domain of the A isoform of FHF2/FGF13 cause an X-linked developmental and epileptic encephalopathy., Whole-exome sequencing identified hemi- and heterozygous variants in the N-terminal domain of the A isoform of FHF2 (FHF2A). The X-linked FHF2 gene (also known as FGF13) has alternative first exons which produce multiple protein isoforms that differ in their N-terminal sequence. The variants were located at highly conserved residues in the FHF2A inactivation particle that competes with the intrinsic fast inactivation mechanism of Nav channels. Functional characterization of mutant FHF2A co-expressed with wild-type Nav1.6 (SCN8A) revealed that mutant FHF2A proteins lost the ability to induce rapid-onset, long-term blockade of the channel while retaining pro-excitatory properties. These gain-of-function effects are likely to increase neuronal excitability consistent with the epileptic potential of FHF2 variants. Our findings demonstrate that FHF2 variants are a cause of infantile-onset developmental and epileptic encephalopathy and underline the critical role of the FHF2A isoform in regulating Nav channel function.[SEP]Relations: FGF13 has relations: protein_protein with PLEKHF2, protein_protein with PLEKHF2, protein_protein with SCN2A, protein_protein with SCN2A, protein_protein with MAPK8IP2, protein_protein with MAPK8IP2, molfunc_protein with growth factor activity, molfunc_protein with growth factor activity, protein_protein with SCN5A, protein_protein with SCN5A. Definitions: variants defined as following: An alteration or difference from a norm or standard.. FHF2 defined as following: This gene plays a role in neural development.. Nav defined as following: A Southern Athabaskan language of the Na-Dene family spoken primarily in the Southwestern United States, especially in the Navajo Nation.. epileptic encephalopathy defined as following: A condition in which epileptiform abnormalities are believed to contribute to the progressive disturbance in cerebral function. Epileptic encephalaopathy is characterized by (1) electrographic EEG paroxysmal activity that is often aggressive, (2) seizures that are usually multiform and intractable, (3) cognitive, behavioral and neurological deficits that may be relentless, and (4) sometimes early death. [PMID:21590624, PMID:23213494]. exons defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.. isoform defined as following: Refers to variants of the same protein which can be separated on special conducting media using electrophoresis. The differences may arise from genetically determined differences in primary structure or by modification of the same primary sequence.. encephalopathy defined as following: A functional and/or structural disorder of the brain caused by diseases (e.g. liver disease, kidney disease), medications, chemicals, and injuries..", "label": "yes"} {"id": "converted_1655", "sentence1": "Are ultraconserved elements depleted among copy number variants (CNVs)?", "sentence2": "We have demonstrated that nonexonic UCEs are depleted among segmental duplications (SDs) and copy number variants (CNVs) and proposed that their ultraconservation may reflect a mechanism of copy counting via comparison. Here, we report that nonexonic UCEs are also depleted among 10 of 11 recent genomewide data sets of human CNVs, including 3 obtained with strategies permitting greater precision in determining the extents of CNVs, Interestingly, human UCEs have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs), We propose that these elements may be interpreted as hallmarks for dose-sensitive genes, particularly for those genes whose gain or loss may be directly implied in neurodevelopmental disorders. Therefore, their presence in genomic imbalances of unknown effect might be suggestive of a clinically relevant condition, Mammalian ultraconserved elements are strongly depleted among segmental duplications and copy number variants., Ultraconserved elements (UCEs) are strongly depleted from segmental duplications and copy number variations (CNVs) in the human genome, suggesting that deletion or duplication of a UCE can be deleterious to the mammalian cell., Interestingly, human UCEs have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs)., We have demonstrated that nonexonic UCEs are depleted among segmental duplications (SDs) and copy number variants (CNVs) and proposed that their ultraconservation may reflect a mechanism of copy counting via comparison., We have demonstrated that nonexonic UCEs are depleted among segmental duplications (SDs) and copy number variants (CNVs) and proposed that their ultraconservation may reflect a mechanism of copy counting via comparison, Interestingly, human UCEs have been reported to be strongly depleted among segmental duplications and benign copy number variants (CNVs), Here, we show that UCEs are significantly depleted among segmental duplications and copy number variants, The depletion of UCEs among copy number variation as well as the significant under-representation of single-nucleotide polymorphisms (SNPs) within UCEs have also revealed their evolutional and functional importance indicating their potential impact on disease, such as cancer[SEP]Relations: Abnormality of the dentition has relations: disease_phenotype_positive with chromosome 6pter-p24 deletion syndrome, disease_phenotype_positive with chromosome 6pter-p24 deletion syndrome, disease_phenotype_positive with chromosome 4q21 deletion syndrome, disease_phenotype_positive with chromosome 4q21 deletion syndrome, disease_phenotype_positive with chromosome 3q29 microduplication syndrome, disease_phenotype_positive with chromosome 3q29 microduplication syndrome, disease_phenotype_positive with chromosome 15q24 deletion syndrome, disease_phenotype_positive with chromosome 15q24 deletion syndrome. mammalian vulva has relations: anatomy_protein_absent with RNU4-78P, anatomy_protein_absent with RNU4-78P. Definitions: SNPs defined as following: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.. neurodevelopmental disorders defined as following: A childhood disorder that has a neurological basis and manifests as a developmental disability.. cancer defined as following: A malignant tumor at the original site of growth.. mammalian cell defined as following: A cell originating from or isolated from an animal of class Mammalia.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"} {"id": "converted_867", "sentence1": "Are psammoma bodies characteristic to meningiomas?", "sentence2": "Psammoma bodies (PBs) are concentric lamellated calcified structures, observed most commonly in papillary thyroid carcinoma (PTC), meningioma, and papillary serous cystadenocarcinoma of ovary but have rarely been reported in other neoplasms and nonneoplastic lesions., Studies on serous cystadenocarcinoma of ovary and meningioma, however, revealed that collagen production by neoplastic cells and subsequent calcification was responsible for the formation of PBs., The existence of some precursor forms of PBs was reported in meningiomas and more recently in PTC, which were mostly in the form of extracellular hyaline globules surrounded by well-preserved neoplastic cells or in a smaller number of cases intracytoplasmic bodies liberated from intact tumor cells., Light microscopy revealed abundant microcysts of varied size throughout the tumor tissue with the presence of whorl formation and psammoma body, but no malignancy was indicated. Electron microscopy further demonstrated interdigitation of the neighboring cell membranes, desmosomes, and intracytoplasmic filaments, which are pathognomonic findings of meningiomas., Unlike SFT, FMs were glycogen-containing and variously exhibited a storiform pattern (13 of 20), psammoma body formation (9 of 20), and calcification of collagen (4 of 20). Immunoreactivities included vimentin (100%), focal to patchy EMA (80%), S-100 protein (80%), collagen IV (25%), and patchy, mild-to-moderate CD34 staining (60%)., In contrast to the inner structure, three-dimensional structure of psammona bodies in meningiomas is not well defined., This study examined three cultured meningiomas, in which surface observation of psammoma bodies might be easier than in the tumor tissues since influence of interposing connective tissue is minimized in tissue culture., The results suggest that psammoma bodies in meningiomas arise in part from meningothelial whorls due to collagen production by tumor cells followed by obliteration and disappearance of tumor cell processes, although some of the alternative pathways for psammoma body formation proposed by other investigators cannot be ruled out by this study., To demonstrate that psammoma bodies in human meningiomas contain type VI collagen and laminin., This is the first report to describe the involvement of type VI collagen in psammoma bodies and whorl formations in meningiomas., Calcification such as psammoma body is sometimes found especially in spinal cord meningioma but ossification of the meningeal tumor was rarely observed., Histological diagnosis was transitional meningioma with psammoma body., In this study we analyzed the morphologic and ultrastructural characteristics of the psammoma bodies in ten meningiomas of different histologic subtypes, characterizing the components of the psammoma body and the elements of the tumor, such as the capillaries and degenerative cells that have been classically considered as initiators of the formation of these calcareous is structures., It is concluded that the mineralization of the psammoma bodies is induced principally by the collagen fibers synthesized by the meningocytes and that the form of mineralization is spherical and growth is radial, controlled by the tumoral cells., CSF cytology revealed benign fibroblastic or meningotheliomatous meningioma with whorl formation and psammoma body., Electron microscopic examination of the calculi showed membrane-bound vesicles and radially precipitated crystals that simulated hydroxyapatite of psammoma body in meningioma., Psammoma bodies in meningiomas resembled those in the choroid plexus stroma., The results of this study suggest that psammoma bodies in the choroid plexus, as in meningiomas, form by a process of dystrophic calcification associated with arachnoid cells and collagen fibres., An early stage of psammoma body formation was seen more frequently in these villous microcores than in the meningocytic whorls., Psammoma bodies in meningocytic whorls were investigated by electron microscopy., Psammoma body formation in the meningocytic whorls may represent degeneration in some whorls of the central cells which contain connective tissue fibers, producing cell debris such as membrane invested vesicles., Twenty human meningiomas were examined for IgG and IgM by the direct immunofluorescence of immunoperoxidase methods, or both. IgG was conspicuously found in and around the blood vessels, whorls, and psammoma bodies. It was also clearly present on the cytoplasmic membranes of the tumour cells., Significance of these findings is briefly discussed including possible humoral immune reactions in regard to whorl and psammoma body formation in meningioma., The fine structure of psammoma bodies was examined in four cases of fibroblastic meningioma., In general, large numbers of various-sized calcified bodies (psammoma bodies) were scattered among the interstitial fibers., These findings suggest that both matrix giant bodies and matrix vesicles may serve as initial nidus of calcification of psammoma bodies in fibroblastic meningioma., Psammoma body formation or dystrophic mineralization and gliosis of the intervening parenchyma was observed in all three cases.[SEP]Relations: skin meningioma has relations: disease_disease with meningioma (disease), disease_disease with meningioma (disease). benign neoplasm of meninges has relations: disease_disease with benign meningioma, disease_disease with benign meningioma. benign meningioma has relations: disease_disease with benign neoplasm of meninges, disease_disease with benign neoplasm of meninges, disease_disease with meningioma (disease), disease_disease with meningioma (disease). transitional meningioma has relations: disease_disease with meningioma (disease), disease_disease with meningioma (disease). Definitions: choroid plexus defined as following: A villous structure of tangled masses of BLOOD VESSELS contained within the third, lateral, and fourth ventricles of the BRAIN. It regulates part of the production and composition of CEREBROSPINAL FLUID.. tumor tissue defined as following: A tumor sample, or entire tumor that is removed for microscopic examination.. calculi defined as following: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones.. type VI collagen defined as following: A non-fibrillar collagen that forms a network of MICROFIBRILS within the EXTRACELLULAR MATRIX of CONNECTIVE TISSUE. The alpha subunits of collagen type VI assemble into antiparallel, overlapping dimers which then align to form tetramers.. meningioma defined as following: A grade I, slowly growing meningioma. Only a minority of tumors recur following complete resection.. collagen defined as following: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).. cell membranes defined as following: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.. IgG defined as following: The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.. PBs defined as following: A precise form of proton therapy that uses an electronically guided scanning system and magnets to deliver a proton beam that is millimeters wide. With this system, beam position and depth can be controlled, allowing for highly precise deposition of radiation to be delivered in all three dimensions of the tumor.. meningiomas defined as following: A relatively common neoplasm of the CENTRAL NERVOUS SYSTEM that arises from arachnoidal cells. The majority are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Meningiomas have a predilection to arise from the parasagittal region, cerebral convexity, sphenoidal ridge, olfactory groove, and SPINAL CANAL. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2056-7). fibroblastic meningioma defined as following: A WHO grade I meningioma characterized by the presence of spindle cells that form bundles in a collagen matrix.. collagen IV defined as following: A non-fibrillar collagen found in the structure of BASEMENT MEMBRANE. Collagen type IV molecules assemble to form a sheet-like network which is involved in maintaining the structural integrity of basement membranes. The predominant form of the protein is comprised of two alpha1(IV) subunits and one alpha2(IV) subunit, however, at least six different alpha subunits can be incorporated into the heterotrimer.. laminin defined as following: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion.. papillary serous cystadenocarcinoma defined as following: An adenocarcinoma usually arising from the ovary. It is characterized by the presence of complex micropapillary structures covered by round and cuboidal cells with a high nuclear to cytoplasmic ratio.. capillaries defined as following: The minute vessels that connect arterioles and venules.. meningeal tumor defined as following: Benign and malignant neoplastic processes that arise from or secondarily involve the meningeal coverings of the brain and spinal cord.. serous cystadenocarcinoma defined as following: A malignant cystic or semicystic neoplasm. It often occurs in the ovary and usually bilaterally. The external surface is usually covered with papillary excrescences. Microscopically, the papillary patterns are predominantly epithelial overgrowths with differentiated and undifferentiated papillary serous cystadenocarcinoma cells. Psammoma bodies may be present. The tumor generally adheres to surrounding structures and produces ascites. (From Hughes, Obstetric-Gynecologic Terminology, 1972, p185). PTC defined as following: The evaluation of the liver and biliary tree using a contrast agent injected directly into the liver.. FMs defined as following: Combining with macrophage colony-stimulating factor (M-CSF) receptor ligand and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity by catalysis of the reaction: ATP + a protein-L-tyrosine = ADP + a protein-L-tyrosine phosphate. [GOC:mah, GOC:signaling]. Calcification defined as following: Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.. connective tissue defined as following: Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX.. vimentin defined as following: OBSOLETE. A type of intermediate filament. [ISBN:0716731363]. neoplastic cells defined as following: abnormal cell which divides more than it should or does not die when it should; cells grown in vitro from neoplastic tissue may be established as a neoplastic cell line, and then can be propagated in cell culture indefinitely.. neoplasms defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. S-100 protein defined as following: A family of highly acidic calcium-binding proteins found in large concentration in the brain and believed to be glial in origin. They are also found in other organs in the body. They have in common the EF-hand motif (EF HAND MOTIFS) found on a number of calcium binding proteins. The name of this family derives from the property of being soluble in a 100% saturated ammonium sulfate solution.. papillary thyroid carcinoma defined as following: A differentiated adenocarcinoma arising from the follicular cells of the thyroid gland. Radiation exposure is a risk factor and it is the most common malignant thyroid lesion, comprising 75% to 80% of all thyroid cancers in iodine sufficient countries. Diagnostic procedures include thyroid ultrasound and fine needle biopsy. Microscopically, the diagnosis is based on the distinct characteristics of the malignant cells, which include enlargement, oval shape, elongation, and overlapping of the nuclei. The nuclei also display clearing or have a ground glass appearance.. IgM defined as following: A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally was called a macroglobulin.. desmosomes defined as following: A type of junction that attaches one cell to its neighbor. One of a number of differentiated regions which occur, for example, where the cytoplasmic membranes of adjacent epithelial cells are closely apposed. It consists of a circular region of each membrane together with associated intracellular microfilaments and an intercellular material which may include, for example, mucopolysaccharides. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990; Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). hydroxyapatite defined as following: The mineral component of bones and teeth; it has been used therapeutically as a prosthetic aid and in the prevention and treatment of osteoporosis.. tumor cells defined as following: Cells of, or derived from, a tumor.. transitional meningioma defined as following: A WHO grade I meningioma characterized by the coexistence of meningothelial cells and fibrous architectural patterns.. human defined as following: Members of the species Homo sapiens.. collagen fibres defined as following: A structural protein and connective tissue component in fiber form composed of numerous fine fibrils, which provides strength and flexibility to tissue.. membrane defined as following: A device that is made from or resembles a thin flexible sheet of material.. extracellular defined as following: The space external to the outermost structure of a cell. For cells without external protective or external encapsulating structures this refers to space outside of the plasma membrane. This term covers the host cell environment outside an intracellular parasite. [GOC:go_curators].", "label": "yes"} {"id": "converted_406", "sentence1": "Can botulism poisoning of a pregnant woman harm her fetus?", "sentence2": "Two botulism outbreaks were attributed to commercial ready-to-eat meat products and 3 to foods served in restaurants; several cases were attributed to non-Native home-prepared foods. Three affected pregnant women delivered healthy infants., Botulinum toxin is not expected to be present in systemic circulation following proper intramuscular or intradermal injection. Moreover, BTX-A, which has a high molecular weight, does not appear to cross the placenta. From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus., From the 38 pregnancies reported in the literature, including women who had botulism poisoning during pregnancy, exposure to BTX-A does not appear to increase the risk of adverse outcome in the fetus.[SEP]Relations: poisoning has relations: disease_disease with lead poisoning, disease_disease with lead poisoning, disease_disease with toxic oil syndrome, disease_disease with toxic oil syndrome, disease_disease with methanol poisoning, disease_disease with methanol poisoning, disease_disease with colchicine poisoning, disease_disease with colchicine poisoning, disease_disease with cyanide-induced parkinsonism, disease_disease with cyanide-induced parkinsonism. Definitions: BTX-A defined as following: An injectable formulation of a neurotoxin derived through the fermentation of the Hall strain of Clostridium botulinum type A with neuromuscular transmission inhibitory and analgesic activities. Upon injection into the affected muscle, the heavy chain portion of botulinum toxin type A (BTX-A) binds to the cell membrane of the motor nerve and is internalized via endocytosis. Upon entry, the light chain portion of the toxin is activated and cleaves the protein SNAP-25, thereby preventing the fusion of acetylcholine (ACh)-containing synaptic vesicles with the cell membrane and, so, the release of ACh into the neuromuscular junction; subsequent binding of ACH to motor end-plate nicotinic acid receptors and ACh-mediated muscle contraction are thus blocked. In addition to ACh, BTX-A may inhibit the release of neuropeptides, such as substance P and glutamate, which may contribute to its analgesic activity.. intramuscular defined as following: Intramuscular injection is a route of drug administration via injection into muscle tissue. Aqueous or oleaginous solutions and emulsions or suspensions may be administered. Absorption rates, delay in availability of the drug to the systemic circulation, and duration of effect are perfusion-limited, depend on molecular size of the agent, volume, and osmolarity of the drug solution, fat content of the injection site, and patient physical activity.. botulism defined as following: A disease caused by potent protein NEUROTOXINS produced by CLOSTRIDIUM BOTULINUM which interfere with the presynaptic release of ACETYLCHOLINE at the NEUROMUSCULAR JUNCTION. Clinical features include abdominal pain, vomiting, acute PARALYSIS (including respiratory paralysis), blurred vision, and DIPLOPIA. Botulism may be classified into several subtypes (e.g., food-borne, infant, wound, and others). (From Adams et al., Principles of Neurology, 6th ed, p1208). poisoning defined as following: Used with drugs, chemicals, and industrial materials for human or animal poisoning, acute or chronic, whether the poisoning is accidental, occupational, suicidal, by medication error, or by environmental exposure.. foods defined as following: Substances taken in by the body to provide nourishment..", "label": "no"} {"id": "converted_4483", "sentence1": "Is resistance training usually associated with increasing muscle hypertrophy?", "sentence2": "While traditional resistance exercises have been widely used to promote muscle strength and hypertrophy in the elderly, , These findings suggest that in young untrained men, progressing from a training frequency of once per week to a training frequency of 5 times per week with equated volume produces similar gains in LBM and muscle strength as a constant training frequency of once per week, over an 8-week training period., Resistance training is one of the effective methods to overcome a decline in muscle mass,, Therefore, in RT prescription for elbow flexors hypertrophy, single-joint exercises such as BC should be emphasized, Our studies establish that resistance training in older adults with type 2 diabetes results in muscle fiber hypertrophy, despite a greater accumulation of inflammatory cytokine transcripts in muscle., Resistance training results in muscle hypertrophy and improves glycemic control in patients with type 2 diabetes., Resistance training (RT) is a popular method of conditioning to enhance sport performance as well as an effective form of exercise to attenuate the age-mediated decline in muscle strength and mass., Enzyme activities, reflecting oxidative potential; decrease during long-term heavy resistance training, resulting in muscle hypertrophy., Optimal adaptations to resistance training (muscle hypertrophy and strength increases) also seem to occur in the late afternoon, which is interesting, since cortisol and, particularly, testosterone (T) concentrations are higher in the morning., Heavy resistance training is associated with increased body weight, lean body mass, and muscle cross-sectional area., The implications for this are (a) athletes are advised to coincide training times with performance times, and (b) individuals may experience greater hypertrophy and strength gains when resistance training protocols are designed dependent on individual T response., Therefore, the combination of resistance training and overexpression of IGF-I induced greater hypertrophy than either treatment alone., The intake of protein after resistance training increases plasma amino acids, which results in the activation of signaling molecules leading to increased muscle protein synthesis (MPS) and muscle hypertrophy., The rate and amount of muscle hypertrophy associated with resistance training is influenced by a wide array of variables including the training program, plus training experience, gender, genetic predisposition, and nutritional status of the individual., Resistance training is commonly prescribed to enhance strength/power qualities and is achieved via improved neuromuscular recruitment, fiber type transition, and/ or skeletal muscle hypertrophy., The mechanisms responsible for the changes in basal post-absorptive protein turnover and its impact on muscle hypertrophy following resistance exercise training are unknown., It has been proposed that protein supplementation during resistance exercise training enhances muscle hypertrophy., BACKGROUND: Effects of resistance training on muscle strength and hypertrophy are well established in adults and younger elderly., Chronic resistance training induces increases in muscle fibre cross-sectional area (CSA), otherwise known as hypertrophy. , Resistance training of healthy young men typically results in muscle hypertrophy and a shift in vastus lateralis composition away from type IIx fibers to an increase in IIa fiber content, In resistance training, it has been empirically accepted that muscle hypertrophy is developed by low intensity and high volume training, while muscle strength and power are developed by high intensity and low volume training. , gh intensity resistance training (HIRT) has led to increased protein synthesis, along with muscle hypertrophy measured at the whole body, whole muscle, and muscle fibre levels, in older adults. Typica, t has been well documented that the increase in strength over the first few weeks of resistance training (i.e. acute) has a strong underlying neural component and further enhancement in strength with long-term (i.e. chronic) resistance training is due to muscle hypertrophy. For, Low-intensity blood flow restricted (LI-BFR) resistance training has been shown to produce comparable increases in muscle hypertrophy to traditional high-intensity (HI) resistance training. Ho, r adaptations caused by resistance training include increased cross-sectional area of the muscle (hypertrophy, hyperplasia, or both), selective hypertrophy of fast twitch fibers, decreased or maintained mitochondrial number and capillary density of muscle, and possible changes in energy sources. Changes in nerv, Skeletal muscle hypertrophy following resistance training is accompanied by a fiber type-specific increase in satellite cell content in elderly men, High-intensity resistance (HIR) training has been associated with muscle hypertrophy and decreased microvascular density that might produce a blood flow limitation. , The rate and amount of muscle hypertrophy associated with resistance training is influenced by a wide array of variables including the training program, plus training experience, gender, genetic predisposition, and nutritional status of the individual, CONCLUSION: The results of this study suggest that pBFR can stimulate muscle hypertrophy to the same degree to that of high-intensity resistance trainin, It is universally accepted that resistance training promotes increases in muscle strength and hypertrophy in younger and older populations, Resistance training (RT) is a popular method of conditioning to enhance sport performance as well as an effective form of exercise to attenuate the age-mediated decline in muscle strength and mass, Resistance training of healthy young men typically results in muscle hypertrophy and a shift in vastus lateralis composition away from type IIx fibers to an increase in IIa fiber content., Resistance training increases muscle size (i.e., causes hypertrophy) and muscle strength, particularly in untrained individuals., Hypertrophy is widely believed to be one of the mechanisms (i.e., a mediator) by which resistance training increases strength., Chronic resistance training induces increases in muscle fibre cross-sectional area (CSA), otherwise known as hypertrophy., The aim of the study was to determine whether it is possible to improve both maximum and rapid force production using resistance training that is typically used to induce muscle hypertrophy in previously untrained older men., Is an Energy Surplus Required to Maximize Skeletal Muscle Hypertrophy Associated With Resistance Training., We conclude that resistance training of prediabetic obese subjects is effective at changing muscle, resulting in fiber hypertrophy and increased type IIx fiber content, and these changes continue up to 16 wk of training.NEW & NOTEWORTHY Obese, insulin-resistant men responded to 16 wk of progressive resistance training with muscle hypertrophy and increased strength and a shift in muscle fiber composition toward fast-twitch, type IIx fibers., BACKGROUND: Effects of resistance training on muscle strength and hypertrophy are well established in adults and youn, Increments in the cross-sectional area of muscle after resistance training can be primarily attributed to fibre hypertrophy., However, no data are reported in the literature to describe and compare the efficacy of the different hypertrophic resistance training strategies in hypoxia.Moreover, improvements in sprinting, jumping, or throwing performance have also been described at terrestrial altitude, encouraging research into the speed of explosive movements at altitude., We conclude that a program of resistance exercise can be safely carried out by elderly women, such a program significantly increases muscle strength, and such gains are due, at least in part, to muscle hypertrophy.[SEP]Relations: Skeletal muscle hypertrophy has relations: phenotype_phenotype with Generalized muscle hypertrophy, phenotype_phenotype with Generalized muscle hypertrophy, phenotype_phenotype with Muscle hypertrophy of the lower extremities, phenotype_phenotype with Muscle hypertrophy of the lower extremities, disease_phenotype_positive with rippling muscle disease, disease_phenotype_positive with rippling muscle disease, disease_phenotype_positive with myostatin-related muscle hypertrophy, disease_phenotype_positive with myostatin-related muscle hypertrophy, phenotype_phenotype with Marked muscular hypertrophy, phenotype_phenotype with Marked muscular hypertrophy. Definitions: hyperplasia defined as following: An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells.. muscle fiber defined as following: OBSOLETE. The contractile fibers, composed of actin, myosin, and associated proteins, found in cells of smooth or striated muscle. [GOC:mah, ISBN:0815316194]. testosterone defined as following: A synthetic form of the endogenous androgenic steroid testosterone. In vivo, testosterone is irreversibly converted to dihydrotestosterone (DHT) in target tissues by the enzyme 5-alpha reductase. Testosterone or DHT ligand-androgen receptor complexes act as transcription factor complexes, stimulating the expression of various responsive genes. DHT binds with higher affinity to androgen receptors than testosterone, activating gene expression more efficiently. In addition, testosterone is irreversibly converted to estradiol by the enzyme complex aromatase, particularly in the liver and adipose tissue. Testosterone and DHT promote the development and maintenance of male sex characteristics related to the internal and external genitalia, skeletal muscle, and hair follicles; estradiol promotes epiphyseal maturation and bone mineralization. Due to rapid metabolism by the liver, therapeutic testosterone is generally administered as an ester derivative.. muscle hypertrophy defined as following: The enlargement or overgrowth of all or part of an organ due to an increase in size (not length) of individual muscle fibers without cell division. In the case of skeletal muscle cells this happens due to the additional synthesis of sarcomeric proteins and assembly of myofibrils. [GOC:mtg_muscle]. IGF-I defined as following: A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. muscle defined as following: Contractile tissue that produces movement in animals.. hypoxia defined as following: A disorder characterized by a decrease in the level of oxygen in the body.. cortisol defined as following: The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.. type 2 diabetes defined as following: A type of diabetes mellitus that is characterized by insulin resistance or desensitization and increased blood glucose levels. This is a chronic disease that can develop gradually over the life of a patient and can be linked to both environmental factors and heredity.. hypertrophy defined as following: General increase in bulk of a part or organ due to CELL ENLARGEMENT and accumulation of FLUIDS AND SECRETIONS, not due to tumor formation, nor to an increase in the number of cells (HYPERPLASIA)..", "label": "yes"} {"id": "converted_4213", "sentence1": "Is capmatinib effective for glioblastoma?", "sentence2": "CONCLUSION: The combination of INC280/buparlisib resulted in no clear activity in patients with recurrent PTEN-deficient glioblastoma. [SEP]Relations: adult glioblastoma has relations: disease_disease with glioblastoma (disease), disease_disease with glioblastoma (disease), disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult spinal cord glioblastoma, disease_disease with adult spinal cord glioblastoma. Definitions: glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO).", "label": "no"} {"id": "converted_3580", "sentence1": "Can discharge destinations be accurately predicted using the Risk Assessment and Prediction Tool (RAPT)?", "sentence2": "CONCLUSION: Our analysis identified age, lower lumbar/lumbosacral surgery, and RAPT walk score as independent predictors of discharge to SNF, and demonstrated superior predictive power compared with the total RAPT Score when combined in a novel grading scale. , PURPOSE: The aim of this study was to evaluate the value of conventional factors, the Risk Assessment and Predictor Tool (RAPT) and performance-based functional tests as predictors of delayed recovery after total hip arthroplasty (THA)., CONCLUSIONS: The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort. , The RAPT allows for identification of patients who are likely to be discharged home or to rehabilitation, which may facilitate preoperative planning of postoperative care. Additionally, it identifies intermediate-risk patients and could be used to implement targeted interventions to facilitate discharge home in this group of patients., RESULTS: Overall predictive accuracy was 78%. , OBJECTIVE: To assess the relevance of the RAPT (Risk Assessment and Prediction Tool), among a cohort of patients undergoing total hip arthroplasty (THA)., CONCLUSION: This study confirmed the usefulness of the RAPT to help in patient orientation decision after total hip arthroplasty. , CONCLUSIONS\n\nThe RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort., RAPT scores<6 and >10 (of 12) predicted with >90% accuracy discharge to inpatient rehabilitation and home, respectively., The RAPT allows for identification of patients who are likely to be discharged home or to rehabilitation, which may facilitate preoperative planning of postoperative care., The Risk Assessment and Prediction Tool (RAPT) is a preoperative survey constructed to predict discharge disposition after total joint arthroplasty (TJA)., CONCLUSIONS The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort., The Risk Assessment and Prediction Tool (RAPT) is a preoperative survey constructed to predict discharge disposition after total joint arthroplasty (TJA)., A low RAPT score is reported to indicate a high risk of needing any form of inpatient rehabilitation after TJA, including short-term nursing facilities., CONCLUSIONS\nThe RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort., CONCLUSIONS: The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort., BACKGROUND: The Risk Assessment and Prediction Tool (RAPT) is used to predict patient discharge disposition after total joint arthroplasty., CONCLUSIONS: The RAPT accurately predicted discharge disposition for high- and low-risk patients in our cohort.[SEP]", "label": "yes"} {"id": "converted_3761", "sentence1": "Do nematodes contain architectural proteins like CTCF?", "sentence2": "A mode of genetic regulation that involves insulators and insulator binding proteins to establish independent transcriptional units is currently not known in nematodes including Caenorhabditis elegans. , the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans., he most highly enriched motif (LM1) corresponds to the X-box motif known from yeast and nematode, uggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. We , of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1. In contrast to earlier st, SULTS: While orthologs for other insulator proteins were absent in all 35 analysed nematode species, we find orthologs of CTCF in a subset of nematodes. A, Loss of the insulator protein CTCF during nematode evolution, que secondary loss of CTCF from several nematodes is paralleled by a loss of two of its interactors, the polycomb repressive complex subunit SuZ12 and the multifunctional transcription factor TYY1. In con, level. A mode of genetic regulation that involves insulators and insulator binding proteins to establish independent transcriptional units is currently not known in nematodes including Caenorhabditis , suggest that the insulator protein CTCF has been secondarily lost in derived nematodes like C. elegans. W, Loss of the insulator protein CTCF during nematode evolution.[SEP]Relations: Protein S human has relations: drug_drug with Nefazodone, drug_drug with Nefazodone, drug_drug with Loracarbef, drug_drug with Loracarbef, drug_drug with Cefditoren, drug_drug with Cefditoren, drug_drug with Tazobactam, drug_drug with Tazobactam, drug_protein with PROC, drug_protein with PROC. Definitions: nematode defined as following: class of unsegmented helminths with fundamental bilateral symmetry and secondary triradiate symmetry of the oral and esophageal structures; many species are parasites.. CTCF defined as following: CCN family member 2 (349 aa, ~38kDa) is encoded by the human CCN2 gene. This protein plays a role in the promotion of proliferation and differentiation of chondrocytes and also mediates heparin- and divalent cation-dependent cell adhesion in many different cell types.. C. elegans defined as following: A species of nematode that is widely used in biological, biochemical, and genetic studies.. Caenorhabditis defined as following: A genus of small free-living nematodes. Two species, CAENORHABDITIS ELEGANS and C. briggsae are much used in studies of genetics, development, aging, muscle chemistry, and neuroanatomy.. yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement..", "label": "no"} {"id": "converted_4125", "sentence1": "Is vocimagene amiretrorepvec effective for glioblastoma?", "sentence2": "CONCLUSIONS: These results support an immune-related mechanism of action for Toca 511 and Toca FC, and suggest that molecular and immunologic signatures are related to clinical benefit from treatment., The median OS was 11.10 months for the Toca 511/FC group and 12.22 months for the control group (hazard ratio, 1.06; 95% CI 0.83, 1.35; P = .62). The secondary end points did not demonstrate statistically significant differences. The rates of adverse events were similar in the Toca 511/FC group and the SOC control group.Conclusions and Relevance: Among patients who underwent tumor resection for first or second recurrence of glioblastoma or anaplastic astrocytoma, administration of Toca 511 and Toca FC, compared with SOC, did not improve overall survival or other efficacy end points.[SEP]Relations: adult glioblastoma has relations: disease_disease with glioblastoma (disease), disease_disease with glioblastoma (disease), disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult infiltrating astrocytic neoplasm, disease_disease with adult spinal cord glioblastoma, disease_disease with adult spinal cord glioblastoma. anaplastic astrocytoma has relations: contraindication with Temsirolimus, contraindication with Temsirolimus, contraindication with Sirolimus, contraindication with Sirolimus. Definitions: molecular defined as following: Relating to or produced by or consisting of molecules.. glioblastoma defined as following: The most malignant astrocytic tumor (WHO grade 4). It is composed of poorly differentiated neoplastic astrocytes and is characterized by the presence of cellular polymorphism, nuclear atypia, brisk mitotic activity, vascular thrombosis, microvascular proliferation, and necrosis. It typically affects adults and is preferentially located in the cerebral hemispheres. (Adapted from WHO). anaplastic astrocytoma defined as following: A central nervous system tumor with morphological features of anaplastic astrocytoma in which there is insufficient information on the IDH genes status..", "label": "no"} {"id": "converted_1854", "sentence1": "Is vortioxetine effective for treatment of depression?", "sentence2": "Vortioxetine is the most recently approved medication for the treatment of major depressive disorder (MDD). , [Vortioxetine: a new antidepressant to treat depressive episodes]., Vortioxetine is a new antidepressant, which mechanism of action is multimodal, targeting the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT3, 5-HT7 receptors and the serotonin transporter (5-HTT). , In short-term studies (8 weeks), vortioxetine is more efficacious than placebo in decreasing depressive symptoms as measured by the MADRS total score, response rate (vortioxetine: 53.2% vs placebo: 35.2%) and remission rate (vortioxetine: 29.2% vs placebo: 19.3%). In a long-term study (52 weeks), vortioxetine is also superior to placebo in preventing relapses and recurrences. Moreover, in second line treatment, after failure of a first line selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrin reuptake inhibitor (SNRI), vortioxetine is superior to agomelatine in improving depressive symptoms and achieving response and remission. , Against this background, we feature the novel antidepressants vortioxetine, vilazodone and milnacipran/levomilnacipran with regard to their serotonin receptor targets such as the 5-HT1A, 5-HT3 and 5-HT7 which may account for their specific effects on certain symptoms of depression (e.g. cognition and anxiety) as well as a characteristic side-effect profile., CONCLUSION: Vortioxetine dominated venlafaxine XR in South Korea and is a relevant treatment option for MDD patients initiating or switching therapy., Vortioxetine: a New Treatment for Major Depressive Disorder., INTRODUCTION: Vortioxetine is a structurally novel medication that has recently been approved for treatment of major depressive disorder (MDD)., EXPERT OPINION: Results of placebo-controlled trials suggest efficacy and an overall safety profile comparable to existing first-line antidepressants. , The authors suggest that vortioxetine is currently a good second-line antidepressant option and shows promise, pending additional long-term data, to become a first-line antidepressant option., Clinical studies indicate that vortioxetine is effective in the treatment of major depression, though there is no suggestion of superiority over active comparators., Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day., Vortioxetine was significantly more effective than was placebo, with a standardized mean difference (SMD) of -0.118 (95% CIs, -0.203 to -0.033, P = 0.007)., Vortioxetine for the treatment of depression., Vortioxetine for the treatment of major depression., Vortioxetine (Lu-AA-21004; 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine hydrobromide) is a novel orally active molecule that is being investigated by Lundbeck and Takeda for the treatment of major depression and generalized anxiety disorders., Vortioxetine (Lu AA21004) is a multi-modal antidepressant in clinical development for the treatment of major depressive disorder (MDD)., A randomized, double-blind, fixed-dose study comparing the efficacy and tolerability of vortioxetine 2.5 and 10 mg in acute treatment of adults with generalized anxiety disorder., Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day., Secondary endpoints included response and remission rates, anxiety symptoms(Hamilton Anxiety Rating Scale), Clinical Global Impression, overall functioning (Sheehan Disability Scale), health-related quality of life(EuroQol 5 Dimensions), productivity (work limitation questionnaire) and family functioning (Depression and Family Functioning Scale).RESULTS: Primary endpoint noninferiority was established and vortioxetine (n = 252) was superior to agomelatine (n = 241) by 2.2 MADRS points (p<0.01)., Vortioxetine (Lu AA21004) is an antidepressant with a mechanism of action thought to be related to a combination of 2 pharmacologic actions: direct modulation of several receptors and inhibition of the serotonin transporter.To evaluate the efficacy of vortioxetine 10 and 20 mg once daily in outpatients with major depressive disorder.This 8-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study was conducted from July 2010 to January 2012 among adults with a primary diagnosis of recurrent major depressive disorder (DSM-IV-TR).Eligible subjects were randomized in 1:1:1 ratio to 1 of 3 treatment arms: vortioxetine 10 mg, vortioxetine 20 mg, or placebo once daily for 8 weeks., Vortioxetine (Lu AA21004) is a new antidepressant that combines a number of neurotransmitter reuptake and receptor effects that have been thought to predict efficacy as a treatment for depressive and anxiety disorders.This review summarizes the pharmacology and neurobiology of vortioxetine, In the study of elderly patients, vortioxetine 5 mg (n = 136) improved 12-item Health Status Questionnaire scores significantly more than placebo (n = 148) for the domains of health perception (10.4, P < 0.0001, SES of 0.54), mental health (7.9, P < 0.001, SES of 0.44), and energy (6.4, P < 0.05, SES of 0.28) (FAS, mixed model for repeated measures).Vortioxetine yielded significant, meaningful HRQoL improvements in 6 MDD studies of 6 to 8 weeks duration., All references included were published between 1999 and 2014.All studies that included humans and were published in English, with data describing vortioxetine for the treatment of MDD, were reviewed.Vortioxetine is a novel multimodal antidepressant agent, which inhibits the 5-HT transporter protein, acts as a 5-HT3 antagonist, 5-HT1A receptor agonist, 5-HT7 receptor antagonist, and a partial agonist of the 5-HT1B receptor, Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day, Vortioxetine is an antidepressant with multimodal activity which has shown efficacy in major depressive disorder (MDD) patients in six of ten short-term, randomized, placebo-controlled trials (completed end 2012).We performed meta-regression analyses to indirectly compare vortioxetine to seven marketed antidepressants with different mechanisms of action, Data were available from 51 human trials involving vortioxetine, and included a total of 7,666 healthy volunteers and patients with a diagnosis of major depressive disorder (MDD) or generalized anxiety disorder who were exposed to at least 1 dose of vortioxetine for a total of 2,743 patient-years.Vortioxetine was effective in treating MDD in the United States at a dose of 20 mg/d, Vortioxetine is a recently approved multimodal antidepressant with anxiolytic properties in preclinical studies.This double-blind, placebo-controlled study assessed the efficacy and tolerability of vortioxetine in subjects with a primary diagnosis of generalized anxiety disorder.Subjects (n = 457) were randomized 1:1:1 to treatment with placebo or vortioxetine 2.5 or 10 mg once daily, There was a significant difference for nausea between the two groups (OR=3.01, 95 % CI=2.22-4.09, Z=7.08, P=0.00001), but no significant differences were observed for the other four adverse effects.CONCLUSIONS: For the treatment of major depressive disorder, our results show that a dose of 5 mg/day vortioxetine was more effective, but more easily induced nausea, compared to placebo., The efficacy and safety of 5 mg/d Vortioxetine compared to placebo for major depressive disorder: A meta-analysis., Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder., Vortioxetine in the treatment of adult patients with major depressive disorder: a meta-analysis of randomized double-blind controlled trials., Vortioxetine has been effective in various animal models of depression and anxiety and clinical studies have shown the antidepressant and antianxiety properties of vortioxetine in a dose range of 5-20 mg/day. , Clinical studies indicate that vortioxetine is effective in the treatment of major depression, though there is no suggestion of superiority over active comparators., The incidence of treatment-emergent adverse events was significantly higher in the duloxetine group than in the vortioxetine group.Duloxetine was more effective but less well-tolerated than vortioxetine in MDD., There was no significant difference in discontinuation rates between vortioxetine and comparators owing to inefficacy (OR 0.983, 95% CI 0.585 to 1.650), whereas discontinuation owing to AEs was significantly less common in the vortioxetine than in the comparator group (OR 0.728, 95% CI 0.554 to 0.957).Studies examining the role of vortioxetine in the treatment of MDD are limited.Although our results suggest that vortioxetine may be an effective treatment option for MDD, they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a l, We performed a meta-analysis to increase the statistical power of these studies and enhance our current understanding of the role of vortioxetine in the treatment of MDD.We performed an extensive search of databases and the clinical trial registry., BACKGROUND: Vortioxetine is a recently approved multimodal antidepressant with anxiolytic properties in preclinical studies.OBJECTIVE: This double-blind, placebo-controlled study assessed the efficacy and tolerability of vortioxetine in subjects with a primary diagnosis of generalized anxiety disorder.METHODS: Subjects (n = 457) were randomized 1:1:1 to treatment with placebo or vortioxetine 2.5 or 10 mg once daily., Vortioxetine significantly improved objective and subjective measures of cognitive function in adults with recurrent MDD and these effects were largely independent of its effect on improving depressive symptoms., Furthermore, a statistically significant number of patients with MDD who were on vortioxetine have achieved a greater than or equal to 50% reduction in depression symptoms from baseline., BACKGROUND: Vortioxetine is a novel multimodal compound that has recently been approved by the FDA for the treatment of major depressive disorder (MDD)., Although our results suggest that vortioxetine may be an effective treatment option for MDD, they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of heterogeneous RCTs.., Vortioxetine is an effective agent for the treatment of MDD, but it does not have any clear advantages over other available treatment options.., Vortioxetine was significantly more effective than placebo for acute treatment of major depressive disorder (MDD)., Duloxetine was more effective but less well-tolerated than vortioxetine in MDD., Vortioxetine is an orally administered small molecule developed by Lundbeck A/S for the once-daily treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Vortioxetine received its first global approval for MDD in the USA in September 2013 and regulatory approval for its use in this indication in the EU (where it has received a positive opinion) and Canada is awaited. , This article summarizes the milestones in the development of vortioxetine leading to this first approval for MDD., Vortioxetine was efficacious and well tolerated in the treatment of patients with major depressive disorder., On the primary efficacy endpoint, both vortioxetine doses were statistically significantly superior to placebo, with a mean difference to placebo (n=158) of -5.5 (vortioxetine 15 mg, P<0.0001, n=149) and -7.1 MADRS points (vortioxetine 20 mg, P<0.0001, n=151)., The change in the severity of depressive and anxiety symptoms was maintained throughout the study as reflected by a 24-item Hamilton Depression Scale total score of 8.2 at week 52 (from 17.6 at open-label baseline) in the observed case data set., Vortioxetine is a multi-modal antidepressant that functions as a human 5-HT3A and 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist, and inhibitor of the serotonin transporter. , Approval for the treatment of MDD was based on a clinical development programme that included six positive 6-8 week studies, including one study in elderly people, and one positive maintenance study in adults., Vortioxetine represents another option for the treatment of MDD. , The multimodal compounds vortioxetine and vilazodone are examples of this approach with diverse mechanisms, and their different clinical effects will provide valuable insights into serotonergic modulation of glutamate transmission for the potential treatment of depression and associated cognitive dysfunction., Two new antidepressant drugs, vilazodone (marketed in the USA) and vortioxetine (in development) incorporate partial 5-HT1A-R agonist properties with SERT blockade., Novel drugs in development include those that combine multiple simultaneous pharmacologic mechanisms in addition to SERT inhibition within the same molecule, such as vilazodone (combining 5HT1A partial agonism with SERT inhibition), triple reuptake inhibitors (combining norepinephrine and dopamine reuptake inhibition with SERT inhibition), and vortioxetine, a multimodal antidepressant combining actions at the G protein receptor mode (5HT1A and 5HT1B partial agonism and 5HT7 antagonism), at the ion channel mode (5HT3 antagonism) as well as the neurotransmitter transporter mode (SERT inhibition). , In this study of adults with MDD treated for 8 weeks with vortioxetine 2.5 mg or 5 mg per day, reductions in depression symptoms were not statistically significant compared with placebo. , However, on the basis of these findings, vortioxetine (2.5, 5, 10 mg/day) demonstrated a favourable safety and tolerability profile and maintained effectiveness over 12 months of treatment. , In this study of adults with MDD, 5 mg vortioxetine did not differ significantly from placebo in reducing depression symptoms after 6 wk of treatment., After 8 weeks of treatment with Lu AA21004 10 mg, there was a significant reduction in HDRS-24 total score compared with placebo in adults with MDD., In conclusion, Lu AA21004 was efficacious and well tolerated in the treatment of elderly patients with recurrent major depressive disorder., Thus, Lu AA21004 was effective in preventing relapse of MDD and was well tolerated as maintenance treatment., Findings on secondary outcome measures, using MMRM instead of LOCF, were supportive of likely efficacy for Lu AA21004 5mg and 10mg and duloxetine. , In this study, treatment with 5 mg and 10 mg Lu AA21004 for 6 wk was efficacious and well tolerated in patients with MDD., Results from phase II clinical trials have reported improvement in depression and anxiety symptoms after 6 weeks of treatment. [SEP]Relations: Vortioxetine has relations: drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Paroxetine, drug_drug with Paroxetine, drug_drug with Harmaline, drug_drug with Harmaline, drug_drug with Methadone, drug_drug with Methadone, drug_drug with Cocaine, drug_drug with Cocaine. Definitions: agonist defined as following: An agent that has affinity for a receptor and intrinsic activity at that receptor.. antidepressant defined as following: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.. GAD defined as following: An anxiety disorder characterized by excessive and difficult-to-control worry about a number of life situations. The worry is accompanied by restlessness, fatigue, inability to concentrate, irritability, muscle tension, and/or sleep disturbance and lasts for at least 6 months.. Vortioxetine defined as following: A piperazine derivative that acts as a serotonin reuptake inhibitor, as a 5-HT3 receptor antagonist, and 5-HT1A receptor agonist. It is used for the treatment of anxiety and depression.. FAS defined as following: A teratogenic disorder observed in a newborn or child of a mother who consumed alcohol during pregnancy. Manifestations of the syndrome include low birth weight, atypical facies, microcephaly, failure to thrive, developmental defects, organ dysfunction, mental deficiencies, poor motor coordination and behavioral problems.. SNRI defined as following: Drugs that selectively block or suppress the plasma membrane transport of SEROTONIN and NORADRENALINE into axon terminals and are used as ANTIDEPRESSIVE AGENTS.. neurotransmitter reuptake defined as following: The directed movement of neurotransmitters into neurons or glial cells. This process leads to inactivation and recycling of neurotransmitters. [ISBN:0123668387]. dopamine defined as following: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.. 5-HT1B receptor defined as following: A serotonin receptor subtype found at high levels in the BASAL GANGLIA and the frontal cortex. It plays a role as a terminal autoreceptor that regulates the rate of SEROTONIN release from nerve endings. This serotonin receptor subtype is closely related to and has similar drug binding properties as the 5-HT1D RECEPTOR. It is particularly sensitive to the agonist SUMATRIPTAN and may be involved in mediating the drug's antimigraine effect.. venlafaxine defined as following: A synthetic phenethylamine bicyclic derivative with antidepressant activity. Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak dopamine reuptake inhibitors. This agent may reduce hormone-related vasomotor symptoms. (NCI04). MDD defined as following: Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5). 5-HT1B defined as following: Human HTR1B wild-type allele is located in the vicinity of 6q14.1 and is approximately 3 kb in length. This allele, which encodes 5-hydroxytryptamine receptor 1B protein, plays a role in serotonin-mediated signaling.. 5-HT1A defined as following: 5-hydroxytryptamine receptor 1A (422 aa, ~46 kDa) is encoded by the human HTR1A gene. This protein is involved in both serotonin binding and neurotransmitter-mediated signal transduction.. AEs defined as following: An instrument that consist of an ultra high vacuum scanning microscope column combined with an electron energy analyzer, which can determine the elemental composition of the outer surface of a sample.. anxiety defined as following: Persistent and disabling ANXIETY.. vilazodone defined as following: A selective serotonin (5-HT) reuptake inhibitor (SSRI) and a 5-HT-1A receptor partial agonist, with antidepressant and anti-anxiety activities. Vilazodone inhibits the reuptake of serotonin from the synaptic cleft while stimulating the release of 5-HT into the synaptic cleft. This increases the concentration of 5-HT in the synaptic cleft and potentiates serotonergic neurotransmission in the central nervous system.. cognitive dysfunction defined as following: Interference or disruption of cognitive processes. This term encompasses a large number of problems and issues associated with intellectual functioning and information processing. 2005. 5HT1A defined as following: Human HTR1A wild-type allele is located within 5q11.2-q13 and is approximately 2 kb in length. This allele, which encodes 5-hydroxytryptamine receptor 1A protein, plays a role in both neurotransmitter binding and G protein-coupled receptor signaling. Mutation of the gene is associated with menstrual cycle-dependent periodic fevers.. serotonin transporter defined as following: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of serotonergic neurons. They are different than SEROTONIN RECEPTORS, which signal cellular responses to SEROTONIN. They remove SEROTONIN from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. Regulates signal amplitude and duration at serotonergic synapses and is the site of action of the SELECTIVE SEROTONIN REUPTAKE INHIBITORS.. humans defined as following: Members of the species Homo sapiens.. CIs defined as following: Cytokine-inducible SH2-containing protein (258 aa, ~29 kDa) is encoded by the human CISH gene. This protein is involved in the modulation of signal transduction.. molecule defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. vortioxetine defined as following: A piperazine derivative that acts as a serotonin reuptake inhibitor, as a 5-HT3 receptor antagonist, and 5-HT1A receptor agonist. It is used for the treatment of anxiety and depression..", "label": "yes"} {"id": "converted_4357", "sentence1": "Is MEDI2228 a bispecific antibody?", "sentence2": "We here delineated the molecular and cellular mechanisms underlying novel immunomodulatory effects triggered by BCMA pyrrolobenzodiazepine (PBD) antibody drug conjugate (ADC) MEDI2228 which can augment efficacy of these immunotherapies.[SEP]Relations: molecular system has relations: anatomy_anatomy with gABAergic system, anatomy_anatomy with gABAergic system, anatomy_anatomy with catecholamine system, anatomy_anatomy with catecholamine system, anatomy_anatomy with histaminergic system, anatomy_anatomy with histaminergic system, anatomy_anatomy with serotonergic system, anatomy_anatomy with serotonergic system, anatomy_anatomy with glutamatergic system, anatomy_anatomy with glutamatergic system. Definitions: molecular defined as following: Relating to or produced by or consisting of molecules.. bispecific antibody defined as following: Antibodies, often monoclonal, in which the two antigen-binding sites are specific for separate ANTIGENIC DETERMINANTS. They are artificial antibodies produced by chemical crosslinking, fusion of HYBRIDOMA cells, or by molecular genetic techniques. They function as the main mediators of targeted cellular cytotoxicity and have been shown to be efficient in the targeting of drugs, toxins, radiolabeled haptens, and effector cells to diseased tissue, primarily tumors..", "label": "no"} {"id": "converted_2858", "sentence1": "Has Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) been reported to be a plasminogen receptor in pathogenic bacteria?", "sentence2": " binding of plasminogen (Plg) to bacterial surfaces, as it has been shown that this interaction contributes to bacterial adhesion to host cells, invasion of host tissues, and evasion of the immune system. Several bacterial proteins are known to serve as receptors for Plg including glyceraldehyde-3-phosphate dehydrogenase (GAPDH),, Moreover, several isoforms of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and galectin (GAL) were identified in both antigenic extracts as plasminogen-binding proteins., Purified GAPDH was found to bind human plasminogen and fibrinogen in Far-Western blot and ELISA-based assays., GAPDH exhibits a high affinity for plasmin and a significantly lower affinity for plasminogen., Moreover, several isoforms of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and galectin (GAL) were identified in both antigenic extracts as plasminogen-binding proteins. [SEP]Relations: Protein S human has relations: drug_drug with Tedizolid phosphate, drug_drug with Tedizolid phosphate, drug_drug with Tedizolid phosphate, drug_drug with Tedizolid phosphate, drug_drug with Protocatechualdehyde, drug_drug with Protocatechualdehyde, drug_drug with Protocatechualdehyde, drug_drug with Protocatechualdehyde, drug_drug with Dehydrochloromethyltestosterone, drug_drug with Dehydrochloromethyltestosterone. Definitions: GAPDH defined as following: Glyceraldehyde-3-phosphate dehydrogenase (335 aa, ~36 kDa) is encoded by the human GAPDH gene. This protein is involved in carbohydrate metabolism.. isoforms defined as following: Refers to variants of the same protein which can be separated on special conducting media using electrophoresis. The differences may arise from genetically determined differences in primary structure or by modification of the same primary sequence.. plasminogen-binding proteins defined as following: Alpha-enolase (434 aa, ~47 kDa) is encoded by the human ENO1 gene. This protein is involved in glycolysis and tumor suppression, and acts as a structural lens protein.. bacterial proteins defined as following: Proteins found in any species of bacterium.. plasminogen defined as following: This gene is involved in blood coagulation/hemostasis. It also plays a role in embryonic development, tissue remodeling and inflammation.. plasmin defined as following: A product of the lysis of plasminogen (profibrinolysin) by PLASMINOGEN activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins.. Plg defined as following: Angiostatin (388, ~40 kDa) is encoded by the human PLG gene. This protein fragment is involved in the inhibition of blood vessel formation.. GAL defined as following: Galanin (30 aa, ~3 kDa) is encoded by the human GAL gene. This protein is involved in nociception, secretion of cortisol, growth hormone and insulin, hair follicle development and contraction of smooth muscle cells of the gastrointestinal and genitourinary tracts..", "label": "yes"} {"id": "converted_317", "sentence1": "Have mutations in the Polycomb group been found in human diseases?", "sentence2": "We identify a novel mutation in PHC1, a human orthologue of the Drosophila polyhomeotic member of polycomb group (PcG), which significantly decreases PHC1 protein expression, increases Geminin protein level and markedly abolishes the capacity to ubiquitinate histone H2A in patient cells., In clinical specimens of head and neck cancer, we found that coamplification of BMI1 and AURKA correlated with poorer prognosis., Mutations of EZH2, RUNX1, TP53, and ASXL1 were associated with shorter overall survival independent of the LR-PSS., In this study, we show the high frequency of spontaneous γδ T-cell leukemia (T-ALL) occurrence in mice with biallelic deletion of enhancer of zeste homolog 2 (Ezh2)., Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as EZH2, AEBP2, and SUZ12; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of JARID2 and AEBP2. We observed frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1., A total of 25 different EZH2 mutations were detected in 5.9% of PMF, 1.2% of PPV-MF, and 9.4% of PET-MF patients; most were exonic heterozygous missense changes., In the present investigation we have focused on the candidate region in 6p23, a region that have been found linked to CL/P in several investigations, in the attempt to find out the susceptibility gene provisionally named OFC1. Gene expression experiments in mice embryo of positional candidate genes revealed that JARID2 was highly and specifically expressed in epithelial cells in merging palatal shelves., High expression of EZH2 and amplification of EZH2 was found in 54.1% and 12.0% of ESCCs, respectively., We also observed that HOXA9 levels were significantly inversely correlated with survival and that BMI-1 was overexpressed in cases with 11q23 rearrangements, suggesting that p19(ARF) suppression may be involved in MLL-associated leukemia., We demonstrate that in multiple experimental models of metastatic prostate cancer both BMI1 and Ezh2 genes are amplified and gene amplification is associated with increased expression of corresponding mRNAs and proteins., he EZH2 gene amplification was significantly (P < 0.05) associated with increased EZH2 protein expression., The third tumor showed a t(6p;10q;10p) as the sole karyotypic abnormality, leading to the fusion of PHF1 with another partner, the enhancer of polycomb (EPC1) gene from 10p11; EPC1 has hitherto not been associated with neoplasia.[SEP]Relations: Protein S human has relations: drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide, drug_drug with Polythiazide. Definitions: EZH2 defined as following: Histone-lysine N-methyltransferase EZH2 (746 aa, ~85 kDa) is encoded by the human EZH2 gene. This protein is involved in the regulation of chromatin modification.. epithelial cells defined as following: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.. AEBP2 defined as following: Zinc finger protein AEBP2 (517 aa, ~54 kDa) is encoded by the human AEBP2 gene. This protein is involved in DNA binding, transcriptional repression and histone methylation.. enhancer defined as following: A 50-150bp DNA sequence that increases the rate of transcription of coding sequences. It may be located at various distances and in either orientation upstream from, downstream from or within a structural gene. When bound by a specific transcription factor it increases the levels of expression of the gene, but is not sufficient alone to cause expression. Distinguished from a promoter, that is alone sufficient to cause expression of the gene when bound.. BMI1 defined as following: Polycomb complex protein BMI-1 (326 aa, ~37 kDa) is encoded by the human BMI1 gene. This protein is involved in transcriptional repression during embryonic development.. HOXA9 defined as following: Human HOXA9 wild-type allele is located within 7p15-p14 and is approximately 7 kb in length. This allele, which encodes homeobox protein Hox-A9, plays roles in both the modulation of transcription by RNA polymerase II and the development of the anterio-posterior axis.. ETV6 defined as following: Human ETV6 wild-type allele is located in the vicinity of 12p13 and is approximately 246 kb in length. This allele, which encodes transcription factor ETV6 protein, is involved in the repression of transcription by RNA polymerase II. Several malignancies, particularly leukemias, are linked to chromosomal translocations of this gene.. PRC2 defined as following: A multisubunit polycomb protein complex that catalyzes the METHYLATION of chromosomal HISTONE H3. It works in conjunction with POLYCOMB REPRESSIVE COMPLEX 1 to effect EPIGENETIC REPRESSION.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. RUNX1 defined as following: Runt-related transcription factor 1 (453 aa, ~49 kDa) is encoded by the human RUNX1 gene. This protein is involved in the promotion of gene transcription and hematopoiesis.. NF1 defined as following: An autosomal dominant inherited disorder (with a high frequency of spontaneous mutations) that features developmental changes in the nervous system, muscles, bones, and skin, most notably in tissue derived from the embryonic NEURAL CREST. Multiple hyperpigmented skin lesions and subcutaneous tumors are the hallmark of this disease. Peripheral and central nervous system neoplasms occur frequently, especially OPTIC NERVE GLIOMA and NEUROFIBROSARCOMA. NF1 is caused by mutations which inactivate the NF1 gene (GENES, NEUROFIBROMATOSIS 1) on chromosome 17q. The incidence of learning disabilities is also elevated in this condition. (From Adams et al., Principles of Neurology, 6th ed, pp1014-18) There is overlap of clinical features with NOONAN SYNDROME in a syndrome called neurofibromatosis-Noonan syndrome. Both the PTPN11 and NF1 gene products are involved in the SIGNAL TRANSDUCTION pathway of Ras (RAS PROTEINS).. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. Geminin defined as following: Geminin (209 aa, ~24 kDa) is encoded by the human GMNN gene. This protein is involved in the modulation of DNA replication.. ASXL1 defined as following: Putative Polycomb group protein ASXL1 (1541 aa, ~165 kDa) is encoded by the human ASXL1 gene. This protein may be involved in the modulation of both transcription and chromatin remodeling.. AURKA defined as following: An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION.. region defined as following: The continents and countries situated on those continents; the UNITED STATES and each of the constituent states arranged by region; CANADA and each of its provinces; AUSTRALIA and each of its states; the major bodies of water and major islands on both hemispheres; and selected major cities.. PHF1 defined as following: PHD finger protein 1 (567 aa, ~62 kDa) is encoded by the human PHF1 gene. This protein is involved in DNA damage responses, binding to trimethylated lysine 36 in histone H3 (H3K36me3) and recruitment of the PRC2 complex.. deletions defined as following: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. T-ALL defined as following: A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.. head and neck cancer defined as following: A primary or metastatic malignant neoplasm affecting the head and neck. Representative examples include oral cavity squamous cell carcinoma, laryngeal squamous cell carcinoma, and salivary gland carcinoma.. PcG defined as following: A family of proteins that play a role in CHROMATIN REMODELING. They are best known for silencing HOX GENES and the regulation of EPIGENETIC PROCESSES.. EPC1 defined as following: Enhancer of polycomb homolog 1 (836 aa, ~93 kDa) is encoded by the human EPC1 gene. This protein plays a role in both histone acetyltransferase activity and transcriptional regulation.. Ezh2 genes defined as following: This gene plays a role in chromatin remodeling and transcriptional regulation.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. TP53 defined as following: Human TP53 wild-type allele is located in the vicinity of 17p13.1 and is approximately 19 kb in length. This allele, which encodes cellular tumor antigen p53 protein, plays a role in cell cycle regulation during the G0/G1transition. Alterations of the TP53 gene occur as both somatic and germline mutations in human malignancies in select cancer-prone families with Li-Fraumeni syndrome.. neoplasia defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. human defined as following: Members of the species Homo sapiens..", "label": "yes"} {"id": "converted_3456", "sentence1": "Is Apremilast effective for Behçet’s Syndrome?", "sentence2": "AREAS COVERED: This review provides a digest of all current experience and evidence about pharmacological agents recently described as having a role in the treatment of BS, including interleukin (IL)-1 inhibitors, tocilizumab, rituximab, alemtuzumab, ustekinumab, interferon-alpha-2a, and apremilast., CONCLUSIONS\n\nApremilast was effective in treating oral ulcers, which are the cardinal manifestation of Behçet's syndrome., CONCLUSIONS Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Behçet's syndrome., CONCLUSIONS\nApremilast was effective in treating oral ulcers, which are the cardinal manifestation of Behçet's syndrome., Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Behçet's syndrome., In patients with oral ulcers associated with Behçet's syndrome, apremilast resulted in a greater reduction in the number of oral ulcers than placebo but was associated with adverse events, including diarrhea, nausea, and headache. (, Apremilast is now approved for the treatment of oral ulcer of Behçet syndrome in the United States.[SEP]Relations: Apremilast has relations: drug_drug with Bepotastine, drug_drug with Bepotastine, drug_drug with Bevacizumab, drug_drug with Bevacizumab, drug_drug with Aprepitant, drug_drug with Aprepitant, drug_drug with Bexarotene, drug_drug with Bexarotene, drug_drug with Cefetamet, drug_drug with Cefetamet. Definitions: Apremilast defined as following: An orally bioavailable, small molecule inhibitor of phosphodiesterase 4 (PDE4), with potential anti-inflammatory activity. Upon oral administration, apremilast targets, binds to and inhibits the activity of PDE4, thereby blocking cyclic adenosine monophosphate (cAMP) degradation and increasing intracellular cAMP levels. This may decrease the production of the proinflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha). PDE4 is an enzyme that plays an important role in the degradation of cAMP and in cytokine production in inflammatory cells.. alemtuzumab defined as following: Any monoclonal antibody directed against the cell surface glycoprotein CD52, regardless of the antibody type (e.g., rat, mouse, humanized).. rituximab defined as following: A murine-derived monoclonal antibody and ANTINEOPLASTIC AGENT that binds specifically to the CD20 ANTIGEN and is used in the treatment of LEUKEMIA; LYMPHOMA and RHEUMATOID ARTHRITIS.. headache defined as following: The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.. diarrhea defined as following: An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.. oral ulcers defined as following: A loss of mucous substance of the mouth showing local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue. It is the result of a variety of causes, e.g., denture irritation, aphthous stomatitis (STOMATITIS, APHTHOUS); NOMA; necrotizing gingivitis (GINGIVITIS, NECROTIZING ULCERATIVE); TOOTHBRUSHING; and various irritants. (From Jablonski, Dictionary of Dentistry, 1992, p842). tocilizumab defined as following: A recombinant, humanized IgG1 monoclonal antibody directed against the interleukin-6 receptor (IL-6R) with immunosuppressant activity. Tocilizumab targets and binds to both the soluble form of IL-6R (sIL-6R) and the membrane-bound form (mIL-6R), thereby blocking the binding of IL-6 to its receptor. This prevents IL-6-mediated signaling. IL-6, a pro-inflammatory cytokine that plays an important role in the regulation of the immune response, is overproduced in autoimmune disorders, certain types of cancers and possibly various other inflammatory conditions..", "label": "yes"} {"id": "converted_581", "sentence1": "Is CD99 encoded by MIC2 gene?", "sentence2": "We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6, We obtained the final diagnosis of ES/PNET by immunohistochemical molecular study with positive staining for the MIC2 gene product (CD99) and a Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement, CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions, CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene, The surgical specimens showed small round cell tumor with positive staining for MIC2 gene product (CD99), CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene., The leukocyte surface molecule CD99 is an integral membrane glycoprotein encoded by the E2/MIC2 gene., Human CD99, which is encoded by the mic2 gene, is a ubiquitous 32 kDa transmembrane protein., Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1., The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene., CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions., CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism coregulated with the polymorphism of the XG blood group gene., CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism co-regulated with the Xga blood group polymorphism., Homology searches resulted in finding homologous sequences (totally about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T lymphocytes., Although considered a specific marker for Ewing's sarcoma/peripheral neuroectodermal tumour, the MIC2 gene product (CD99) has been immunolocalised in a variety of human tumours., MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes., Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1., The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene., CD99 (MIC2) regulates the LFA-1/ICAM-1-mediated adhesion of lymphocytes, and its gene encodes both positive and negative regulators of cellular adhesion., Relation of neurological marker expression and EWS gene fusion types in MIC2/CD99-positive tumors of the Ewing family., The Ewing family of tumors (EFT) is characterized by high MIC2/CD99 expression and specific EWS/ETS gene rearrangements, resulting in different chimeric transcripts., The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene., Monoclonal antibody (MAb) HBA71, which was raised against Ewing's sarcoma cells, recognizes a cell-surface glycoprotein, p30/32MIC2, that is encoded by the MIC2 gene in the pseudoautosomal region of human chromosomes X and Y., Monoclonal antibodies (mAbs) directed against E2, a 32-kDa transmembrane protein encoded by the MIC2 gene located in the pseudoautosomal region, induce a transbilayer movement of phosphatidylserine and, to a lesser extent, phosphatidylethanolamine in human thymocytes and a Jurkat T lymphocytes., Homology searches resulted in finding homologous sequences (totally about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T lymphocytes., CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene, CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions, The surgical specimens showed small round cell tumor with positive staining for MIC2 gene product (CD99), We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6, MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes, Immunohistochemical analysis showed weak to moderate and partial staining for MIC2 (CD99) and WT1, respectively, Human CD99, which is encoded by the mic2 gene, is a ubiquitous 32 kDa transmembrane protein, The leukocyte surface molecule CD99 is an integral membrane glycoprotein encoded by the E2/MIC2 gene, The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene, Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1, MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes, CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism co-regulated with the Xga blood group polymorphism[SEP]Relations: EWSR1 has relations: protein_protein with CDK12, protein_protein with CDK12, protein_protein with CD177, protein_protein with CD177, protein_protein with CUEDC2, protein_protein with CUEDC2. SLC52A2 has relations: protein_protein with ADRB2, protein_protein with ADRB2, protein_protein with CDC23, protein_protein with CDC23. Definitions: T lymphocytes defined as following: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.. CD99 antigen defined as following: A cell adhesion molecule that, in humans, is encoded by a gene on the PSEUDOAUTOSOMAL REGION of SEX CHROMOSOMES. It functions in CELL ADHESION of T-LYMPHOCYTES and ROSETTE FORMATION by ERYTHROCYTES. It is also involved in the migration of LEUKOCYTES through the ENDOTHELIUM BASEMENT MEMBRANE. The 12E7 antigen co-localizes with, but functions independently of PECAM-1.. phosphatidylethanolamine defined as following: A phospholipid with the polar ethanolamine found in phosphoester linkage to diacylglycerol.. E2 defined as following: Isoenergetic transfer of a ubiquitin-like protein (ULP) from one protein to another via the reaction X-SCP + Y -> Y-SCP + X, where both the X-SCP and Y-SCP linkages are thioester bonds between the C-terminal amino acid of SCP and a sulfhydryl side group of a cysteine residue. [GOC:dph]. insertion defined as following: Something inserted or to be inserted.. product defined as following:Participant material that is brought forth (produced) in the act (e.g., specimen in a specimen collection, access or drainage in a placement service, medication package in a dispense service). It does not matter whether the material produced had existence prior to the service, or whether it is created in the service (e.g., in supply services the product is taken from a stock).
. transmembrane protein defined as following: A protein that is an integral membrane protein with a transmembrane region.. cell surface glycoprotein defined as following: Glycoproteins found on the membrane or surface of cells.. Ewing sarcoma defined as following: A small round cell tumor that lacks morphologic, immunohistochemical, and electron microscopic evidence of neuroectodermal differentiation. It represents one of the two ends of the spectrum called Ewing sarcoma/peripheral neuroectodermal tumor. It affects mostly males under age 20, and it can occur in soft tissue or bone. Pain and the presence of a mass are the most common clinical symptoms.. Monoclonal antibodies defined as following: Antibodies produced by a single clone of cells.. EWSR1 defined as following: This gene may play a role in post-transcriptional regulation; however the function remains to be elucidated. Mutations in the gene result in Ewing sarcoma and other tumors.. Ewing's sarcoma defined as following: A small round cell bone tumor that lacks morphologic, immunohistochemical, and electron microscopic evidence of neuroectodermal differentiation. It represents one of the two ends of the spectrum called Ewing sarcoma/peripheral neuroectodermal tumor. It often affects the diaphysis or metaphyseal-diaphyseal portion of long bones. Clinical findings include pain and a mass in the involved area. Fever, anemia, leukocytosis, and an increased sedimentation rate are often seen. X-ray examination reveals osteolytic lesions. The prognosis depends on the stage, anatomic location, and size of the tumor.. membranous defined as following: Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures.. MIC2 defined as following: Human CD99 wild-type allele is located in the vicinity of both Xp22.32 and Yp11.3 and is approximately 50 kb in length. This allele, which encodes CD99 antigen protein, is involved in cell adhesion.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. WT1 defined as following: An embryonal neoplasm characterized by the presence of epithelial, mesenchymal, and blastema components. The vast majority of cases arise from the kidney. A small number of cases with morphologic features resembling Wilms tumor of the kidney have been reported arising from the ovary and the cervix.. phosphatidylserine defined as following: A phospholipid with a polar serine found in phosphoester linkage to diacylglycerol.. pseudoautosomal region defined as following: Homologous chromosomal regions at either end of the X CHROMOSOME or Y CHROMOSOME. These two regions pair regularly at male MEIOSIS and undergo RECOMBINATION. Pseudoautosomal region 1 (PAR1) is located at the tip of the short 'p' arms (Xp22 and Yp11) and Pseudoautosomal region 2 (PAR2) is located at the tip of the long 'q' arms (Xq28 and Yq12).. gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. human defined as following: Members of the species Homo sapiens.. polymorphism defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.. homology defined as following: A gene from one species which corresponds to a gene in another species and that is related via a common ancestral species. These genes retain a similar sequence and function.. CD99 defined as following: CD99 antigen (185 aa, ~19 kDa) is encoded by the human CD99 gene. This protein plays a role in cell adhesion..", "label": "yes"} {"id": "converted_3167", "sentence1": "Can miR-122 target RUNX2?", "sentence2": "MiR-122 functions as a tumor suppressor by inhibiting proliferation and inducing apoptosis, which is achieved by directly targeting RUNX2.[SEP]Relations: MIR122 has relations: bioprocess_protein with gene silencing by miRNA, bioprocess_protein with gene silencing by miRNA, disease_protein with liver cancer, disease_protein with liver cancer, disease_protein with drug-induced liver injury, disease_protein with drug-induced liver injury, disease_protein with acute kidney failure, disease_protein with acute kidney failure, disease_protein with hepatitis B virus infection, disease_protein with hepatitis B virus infection. Definitions: RUNX2 defined as following: Runt-related transcription factor 2 (521 aa, ~57 kDa) is encoded by the human RUNX2 gene. This protein plays a role in the regulation of both bone development and transcription.. MiR-122 defined as following: This gene is involved in the regulation of gene expression and plays a role in the development of hepatocellular carcinoma.. miR-122 defined as following: This gene is involved in the regulation of gene expression and plays a role in the development of hepatocellular carcinoma..", "label": "yes"} {"id": "converted_4586", "sentence1": "Is Mediator present at super enhancers?", "sentence2": "BRD4 and Mediator were found to co-occupy thousands of enhancers associated with active genes., Master transcription factors and mediator establish super-enhancers at key cell identity genes, Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs)., These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator, BRD4 maintains transcription of core stem cell genes such as OCT4 and PRDM14 by occupying their super-enhancers (SEs), large clusters of regulatory elements, and recruiting to them Mediator and CDK9, the catalytic subunit of the positive transcription elongation factor b (P-TEFb), to allow Pol-II-dependent productive elongation., The term 'super-enhancer' has been used to describe groups of putative enhancers in close genomic proximity with unusually high levels of Mediator binding, as measured by chromatin immunoprecipitation and sequencing (ChIP-seq)., Mediator kinase inhibition further activates super-enhancer-associated genes in AML., Furthermore, the binding of SIM2 marks a particular sub-category of enhancers known as super-enhancers. These regions are characterized by typical DNA modifications and Mediator co-occupancy (MED1 and MED12). , Many genes determining cell identity are regulated by clusters of Mediator-bound enhancer elements collectively referred to as super-enhancers. , A number of studies have recently demonstrated that super-enhancers, which are large cluster of enhancers typically marked by a high level of acetylation of histone H3 lysine 27 and mediator bindings, are frequently associated with genes that control and define cell identity during normal development. , Super-enhancers are characterized by high levels of Mediator binding and are major contributors to the expression of their associated genes. [SEP]Relations: Protein S human has relations: drug_drug with Resveratrol, drug_drug with Resveratrol, drug_drug with Resveratrol, drug_drug with Resveratrol, drug_drug with Resveratrol, drug_drug with Resveratrol, drug_drug with Platelet Activating Factor, drug_drug with Platelet Activating Factor, drug_drug with Platelet Activating Factor, drug_drug with Platelet Activating Factor. Definitions: OCT4 defined as following: This gene plays a role in early mammalian development.. Nanog defined as following: This gene plays a role in the underlying pluripotency of inner cell mass and embryonic stem cells.. Sox2 defined as following: Transcription factor SOX-2 protein (317 aa, ~34 kDa) is encoded by the human SOX2 gene. This protein is involved in neural cell progenitor differentiation and neurogenesis.. histone H3 lysine 27 defined as following: The lysine residue found at amino acid position 28 in the histone H3 protein. Methylation of this residue may be a marker for transcriptionally repressed genes.. Mediator defined as following: An agent that acts as a link between parties, objects, or actions.. MED1 defined as following: A form of multiple epiphyseal dysplasia manifesting as normal or mild short stature, pain in the hips and/or knees, progressive deformity of extremities and early onset osteoarthrosis. Specific features include a more pronounced involvement of hip joints and gait abnormality and a shorter adult height. The disease follows an autosomal dominant mode of transmission.. CDK9 defined as following: Cyclin-dependent kinase 9 (372 aa, ~43 kDa) is encoded by the human CDK9 gene. This protein plays a role in the positive regulation of transcriptional elongation.. AML defined as following: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.. BRD4 defined as following: Bromodomain-containing protein 4 (1362 aa, ~152 kDa) is encoded by the human BRD4 gene. This protein plays a role in the mitotic process.. P-TEFb defined as following: A transcriptional elongation factor complex that is comprised of a heterodimer of CYCLIN-DEPENDENT KINASE 9 and one of several CYCLINS including TYPE T CYCLINS and cyclin K. It functions by phosphorylating the carboxy-terminal domain of RNA POLYMERASE II.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. MED12 defined as following: Mediator of RNA polymerase II transcription subunit 12 (2177 aa, ~243 kDa) is encoded by the human MED12 gene. This protein plays a role in the initiation of transcription.. catalytic subunit defined as following: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction..", "label": "yes"} {"id": "converted_944", "sentence1": "Has protein citrullination been implicated in rheumatoid arthritis?", "sentence2": ": Citrullination has become a hot topic within recent years due to its involvement in diseases such as rheumatoid arthritis (RA), multiple sclerosis and fibrosis. , Current literature suggests that increased levels of citrullinated proteins are found in several if not all inflammatory diseases. , Antibodies directed against citrullinated proteins and peptides (ACPAs) are the most specific serological markers available for diagnosing RA. , Citrullination of proteins is well described in rheumatoid arthritis (RA), and hypercitrullination of proteins may be related to inflammation in general. , Some ACPA are remarkably effective as diagnostics in autoimmune disorders, most notably rheumatoid arthritis (RA). Several ACPA can be observed before other clinical RA manifestations are apparent. , Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein/peptide autoantibodies (ACPAs). , Anti-citrullinated peptides as autoantigens in rheumatoid arthritis-relevance to treatment., The implications of citrullination affecting integrin binding in disease open up a new area of study and might have implications for the pathogenesis of inflammatory diseases like rheumatoid arthritis and periodontitis., In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation., Citrullinated collagen II (CII) is a well-known autoantigen in rheumatoid arthritis (RA). , Among the RA-associated autoantibodies, especially anti-citrullinated protein antibodies (ACPAs) have been studied intensively in the last decade., Protein citrullination is a posttranslational modification that has attracted increased attention, especially for its involvement in rheumatoid arthritis (RA)., Identification of citrullinated cellular fibronectin in synovial fluid from patients with rheumatoid arthritis., Cellular fibronectin (cFn) has been implicated in the pathogenesis of rheumatoid arthritis (RA), and we previously demonstrated the presence of citrullinated cFn in rheumatoid synovial tissues. , . In rheumatoid arthritis, PAD4 and protein citrullination are increased in inflamed joints, and anti-citrullinated protein antibodies (ACPAs) form against citrullinated antigens are formed. [SEP]Relations: Anti-citrullinated protein antibody positivity has relations: disease_phenotype_positive with rheumatoid arthritis, disease_phenotype_positive with rheumatoid arthritis. Rheumatoid arthritis has relations: drug_effect with Citalopram, drug_effect with Citalopram, drug_effect with Cevimeline, drug_effect with Cevimeline, drug_effect with Cyclosporine, drug_effect with Cyclosporine, drug_effect with Ropinirole, drug_effect with Ropinirole. Definitions: fibrosis defined as following: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. peptides defined as following: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.. PAD4 defined as following: Human PADI4 wild-type allele is located in the vicinity of 1p36.13 and is approximately 56 kb in length. This allele, which encodes protein-arginine deiminase type-4 protein, plays a role in the post-translational protein modification. Mutation of the gene is associated with susceptibility to rheumatoid arthritis.. rheumatoid arthritis defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. autoantigens defined as following: Endogenous tissue constituents with the ability to interact with AUTOANTIBODIES and cause an immune response.. inflammation defined as following: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.. autoimmune disorders defined as following: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.. periodontitis defined as following: Inflammation and loss of connective tissues supporting or surrounding the teeth. This may involve any part of the PERIODONTIUM. Periodontitis is currently classified by disease progression (CHRONIC PERIODONTITIS; AGGRESSIVE PERIODONTITIS) instead of age of onset. (From 1999 International Workshop for a Classification of Periodontal Diseases and Conditions, American Academy of Periodontology). ACPA defined as following: Myeloblastin (256 aa, ~28 kDa) is encoded by the human PRTN3 gene. This protein is involved in the proteolysis of extracellular matrix proteins.. anti-citrullinated protein antibodies defined as following: Autoantibodies to citrullinated-peptides and proteins.. multiple sclerosis defined as following: An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903). disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. rheumatoid factor defined as following: The determination of the amount of rheumatoid factor antibody present in a sample..", "label": "yes"} {"id": "converted_402", "sentence1": "Is paroxetine effective for treatment of premenstrual dysphoric disorder?", "sentence2": "To evaluate the cost effectiveness of the four medications with a US FDA-approved indication for PMDD: fluoxetine, sertraline, paroxetine and drospirenone plus ethinyl estradiol (DRSP/EE)., All SSRIs (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and clomipramine) were effective in reducing premenstrual symptoms., Paroxetine has been approved for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder, panic disorder (PD), generalised anxiety disorder, post traumatic stress disorder (PTSD), and social anxiety disorder (SAD) in adults, whereas paroxetine CR is approved for the treatment of MDD, SAD, PD and premenstrual dysphoric disorder in adults., Selective serotonin-reuptake inhibitors (SSRIs) have been proven safe and effective for the treatment of PMDD and are recommended as first-line agents when pharmacotherapy is warranted. Currently fluoxetine, controlled-release paroxetine, and sertraline are the only Food and Drug Administration-approved agents for this indication., When compared with placebo, patients treated with paroxetine 20 mg attained a significant reduction in irritability (difference in median percent change: -23.9, 95% CI = -51.3 to -6.2, p = .014; difference in mean absolute change: -18.6, 95% CI = -32.5 to -4.6, p = .007). A statistically significant difference was not observed when the patients treated with the lower dose of paroxetine (10 mg) were compared with placebo. Treatment was well tolerated with no unexpected side effects., Intermittent administration of paroxetine 20 mg significantly reduced irritability symptoms in patients with PMDD., All these women had significant improvements in the HAMA, HAMD, CGI, and PRISM calendar. The rate of response to paroxetine treatment lay between 50% and 78.6% in the continuous-treatment group, and 37.5-93.8% in the intermittent-treatment group, as determined at the study end-point., The present results indicate that paroxetine is effective in both continuous and intermittent treatment of oriental PMDD women, and that the effects of active treatment lasted for six consecutive treatment menstrual cycles., Paroxetine CR is approved for the treatment of major depression, social anxiety disorder, panic disorder and premenstrual dysphoric disorder in adults., Continuous treatment with paroxetine reduced premenstrual symptoms effectively with a response rate of 85%., Intermittent treatment was as effective as continuous treatment in reducing irritability, affect lability, and mood swings, but had a somewhat weaker effect on depressed mood and somatic symptoms., Daily Record of Severity of Problems scores were lower in the paroxetine group compared with the placebo group, although the differences were not statistically significant., However, the mean on-treatment Inventory of Depressive Symptomatology (clinician-rated) score for the paroxetine group was 17.9 +/- 8.3 compared with 31.5 +/- 11.2 in the placebo group (adjusted mean difference = 13.6, P = 0.009)., Response (Clinical Global Impressions Scale score of 1 or 2) occurred in 70% of subjects randomized to paroxetine CR and 10% of those assigned to placebo (chi2(1) = 7.5, P = 0.006)., The US Food and Drug Administration and Health Canada recently approved paroxetine for the treatment of premenstrual dysphoric disorder., Patients treated with either dose of paroxetine CR demonstrated significantly greater improvements on the primary efficacy measure (change from baseline in mean luteal phase VAS-Mood scores) and on the majority of secondary efficacy measures compared with patients randomly assigned to placebo., For the treatment of PMDD, luteal phase dosing with 12.5 mg and 25 mg of paroxetine CR is effective and generally well tolerated., A statistically significant difference was observed in favor of paroxetine CR 25 mg versus placebo on the VAS-Mood (adjusted mean difference = -12.58 mm, 95% CI = -18.40 to -6.76; p < .001) and for paroxetine CR 12.5 mg versus placebo (adjusted mean difference = -7.51 mm, 95% CI = -13.40 to -1.62; p = .013)., Paroxetine CR doses of 12.5 mg/day and 25 mg/day are effective in treating PMDD and are well tolerated., At end point, subjects treated with paroxetine CR (12.5 mg and 25 mg) demonstrated significant improvement in VAS-Mood scores compared with those who received placebo (paroxetine CR 12.5 mg mean treatment difference vs. placebo, -8.7 mm; 95% CI, -15.7, -1.7; p =.015; paroxetine CR 25 mg mean treatment difference vs. placebo, -12.1 mm; 95% CI, -18.9, -5.3; p <.001)., Both doses of paroxetine CR 12.5 mg and 25 mg daily are effective and well tolerated in patients who suffer from PMDD., Of these agents, sertraline, fluoxetine and paroxetine (as an extended-release formulation) are approved by the US FDA for luteal phase, as well as continuous, administration., In well designed placebo-controlled trials in patients with major depressive disorder (including a study in the elderly), social anxiety disorder or premenstrual dysphoric disorder (PMDD), paroxetine CR was consistently superior to placebo with regards to primary endpoints (i.e. mean Hamilton Rating Scale for Depression total score [major depressive disorder], Liebowitz social anxiety scale total score and Clinical Global Impressions-Global Improvement score [social anxiety disorder] and Visual Analogue Scale-Mood score [PMDD])., Paroxetine is a potent selective serotonin reuptake inhibitor (SSRI) with indications for the treatment of depression, obsessive- compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post-traumatic stress disorder, premenstrual dysphoric disorder and chronic headache., Studies having compared the efficiency of antidepressants according to their serotonin activity (paroxetine or sertraline versus maprotiline, that is a selective noradrenaline re-uptake inhibitor), showed that serotonin re-uptake inhibitors were significantly more efficient on all symptoms than maprotiline, that was not more efficient than placebo., Paroxetine is a potent and selective serotonin reuptake inhibitor (SSRI) with currently approved indications for the treatment of depression, obsessive-compulsive disorder, panic disorder and social phobia. It is also used in the treatment of generalized anxiety disorder, post traumatic stress disorder, premenstrual dysphoric disorder and chronic headache., Preliminary data suggest that paroxetine has potential in the treatment of social phobia, premenstrual dysphoric disorder and chronic headache., The effects of active treatment were marked by the first active cycle with luteal phase 17-item Hamilton Rating Scale for Depression scores decreasing from 14.9 (+/- 5.3) to 8.2 (+/- 4.9) in the first, 7.8 (+/- 5.1) in the second, and 7.8 (+/- 6.8) in the third active treatment cycles (F[1,13] = 17.6; p < 0.0001)., The most conservative measure, the Clinical Global Impression (CGI), revealed that 7 of 14 patients had a complete response (CGI = 1 or 2) whereas 4 patients had a partial response (CGI = 3)., These open trial findings are consistent with the notion that paroxetine is effective in the acute phase for the treatment of PDD., The rating of premenstrual irritability, depressed mood, increase in appetite, and anxiety/tension was markedly lower during treatment with paroxetine than before, and this reduction in symptomatology appeared unabated for the entire treatment period.[SEP]Relations: Paroxetine has relations: drug_effect with Dyspnea, drug_effect with Dyspnea, contraindication with bipolar disorder, contraindication with bipolar disorder, drug_effect with Dysphagia, drug_effect with Dysphagia, drug_effect with Dysuria, drug_effect with Dysuria, drug_effect with Dyssynergia, drug_effect with Dyssynergia. Definitions: premenstrual dysphoric disorder defined as following: A condition in which a woman suffers from severe depression, irritability, and tension before MENSTRUATION. Premenstrual dysphoric disorder (PMDD) may involve a wide range of physical or emotional symptoms, which are more severe and debilitating than those seen with premenstrual syndrome (PMS), and which include at least one mood-related symptom. Symptoms usually stop when, or shortly after, menstruation begins.. post-traumatic stress disorder defined as following: A class of traumatic stress disorders with symptoms that last more than one month.. maprotiline defined as following: A bridged-ring tetracyclic antidepressant that is both mechanistically and functionally similar to the tricyclic antidepressants, including side effects associated with its use.. SSRIs defined as following: Any agent that increases the extracellular level of the neurotransmitter serotonin (5-HT) by inhibiting its reuptake into the presynaptic cell. Increased level in the synaptic cleft prolongs the action of 5-HT on the postsynaptic receptor. This type of agent is typically used as an antidepressant and in the treatment of anxiety disorders and some personality disorders. They are also typically effective and used in treating some cases of insomnia.. traumatic stress disorder defined as following: Anxiety disorders manifested by the development of characteristic symptoms following a psychologically traumatic event that is outside the normal range of usual human experience. Symptoms include re-experiencing the traumatic event, increased arousal, and numbing of responsiveness to or reduced involvement with the external world. Traumatic stress disorders can be further classified by the time of onset and the duration of these symptoms.. drospirenone defined as following: A synthetic spironolactone analogue and progestin with progestational and anti-mineralocorticoid activity. Drospirenone binds to the progesterone receptor, the resulting complex becomes activated and binds to specific sites on DNA. This results in a suppression of LH activity and an inhibition of ovulation as well as an alteration in the cervical mucus and endometrium. This leads to an increased difficulty of sperm entry into the uterus and implantation. This drug is used in oral contraceptives.. antidepressants defined as following: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several MONOAMINE OXIDASE INHIBITORS are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents (ANTIDEPRESSIVE AGENTS, TRICYCLIC) also appear to act through brain catecholamine systems. A third group (ANTIDEPRESSIVE AGENTS, SECOND-GENERATION) is a diverse group of drugs including some that act specifically on serotonergic systems.. fluvoxamine defined as following: A selective serotonin reuptake inhibitor that is used in the treatment of DEPRESSION and a variety of ANXIETY DISORDERS.. Paroxetine defined as following: A serotonin uptake inhibitor that is effective in the treatment of depression.. panic disorder defined as following: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait.. ethinyl estradiol defined as following: A semisynthetic alkylated ESTRADIOL with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in ORAL CONTRACEPTIVES.. PDD defined as following: A category of developmental disorders characterized by impaired communication and socialization skills. The impairments are incongruent with the individual's developmental level or mental age. These disorders can be associated with general medical or genetic conditions.. sertraline defined as following: A selective serotonin uptake inhibitor that is used in the treatment of depression.. serotonin defined as following: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.. citalopram defined as following: A furancarbonitrile that is one of the SELECTIVE SEROTONIN REUPTAKE INHIBITORS used as an antidepressant. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from TARDIVE DYSKINESIA in preference to tricyclic antidepressants, which aggravate dyskinesia.. noradrenaline defined as following: A synthetic phenylethylamine that mimics the sympathomimetic actions of the endogenous norepinephrine. Norepinephrine acts directly on the alpha- and beta-adrenergic receptors. Clinically, norepinephrine is used as a peripheral vasoconstrictor that causes constriction of arterial and venous beds via its alpha-adrenergic action. It is also used as a potent inotropic and chronotropic stimulator of the heart mediated through its beta-1 adrenergic action.. irritability defined as following: Abnormal or excessive excitability with easily triggered anger, annoyance, or impatience.. fluoxetine defined as following: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants.. clomipramine defined as following: A tricyclic antidepressant similar to IMIPRAMINE that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine.. obsessive-compulsive disorder defined as following: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension.. PD defined as following: A score of 4 or 5 on a 5-point PET scale with an increase in intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment.. social phobia defined as following: An anxiety disorder characterized by an intense, irrational fear of one or more social or performance situations in which the individual believes that he or she will be scrutinized by others. Exposure to social situations immediately provokes an anxiety response. In adults, the social phobia is recognized as excessive or unreasonable.. SAD defined as following: A syndrome characterized by depressions that recur annually at the same time each year, usually during the winter months. Other symptoms include anxiety, irritability, decreased energy, increased appetite (carbohydrate cravings), increased duration of sleep, and weight gain. SAD (seasonal affective disorder) can be treated by daily exposure to bright artificial lights (PHOTOTHERAPY), during the season of recurrence.. depressed mood defined as following: An emotional state characterized by feelings of sadness, emptiness, and/or tearfulness.. MDD defined as following: Disorder in which five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure. Symptoms include: depressed mood most of the day, nearly every daily; markedly diminished interest or pleasure in activities most of the day, nearly every day; significant weight loss when not dieting or weight gain; Insomnia or hypersomnia nearly every day; psychomotor agitation or retardation nearly every day; fatigue or loss of energy nearly every day; feelings of worthlessness or excessive or inappropriate guilt; diminished ability to think or concentrate, or indecisiveness, nearly every day; or recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt. (DSM-5). paroxetine defined as following: A serotonin uptake inhibitor that is effective in the treatment of depression..", "label": "yes"} {"id": "converted_2277", "sentence1": "Are TAD boundaries in Drosophila depleted in highly-expressed genes?", "sentence2": "Furthermore, we find that these TAD boundaries are present irrespective of the expression and looping of genes located between them., In particular, Hi-C revealed that chromosomes of animals are organized into topologically associating domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression., Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. , The insulator-like, TAD-boundary-like, and TAD-interior-like regions are each enriched for distinct epigenetic marks and are each correlated with different gene expression levels, We conclude that epigenetic modifications, gene density, and transcriptional activity combine to shape the local packing of the A. thaliana nuclear genome., Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions., Our results demonstrate the functional importance of TADs for orchestrating gene expression via genome architecture and indicate criteria for predicting the pathogenicity of human structural variants, particularly in non-coding regions of the human genome., The three-dimensional organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure., Ectopically expressed roX1 and roX2 RNAs target HAS on the X chromosome in trans and, via spatial proximity, induce spreading of the MSL complex in cis, leading to increased expression of neighboring autosomal genes. , Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin., However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes.[SEP]Relations: insect neurogenic region has relations: anatomy_anatomy with embryonic structure, anatomy_anatomy with embryonic structure. X chromosome has relations: cellcomp_protein with PCGF3, cellcomp_protein with PCGF3, cellcomp_protein with SIN3B, cellcomp_protein with SIN3B, cellcomp_protein with PCGF5, cellcomp_protein with PCGF5. chromosome X structural anomaly has relations: disease_disease with partial deletion of chromosome X, disease_disease with partial deletion of chromosome X. Definitions: RNAs defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). chromosome structure defined as following: Structures which are contained in or part of CHROMOSOMES.. TADs defined as following: Tietz syndrome is a genetic hypopigmentation and deafness syndrome characterized by congenital profound bilateral sensorineural hearing loss and generalized albino-like hypopigmentation of skin, eyes and hair.. chromosomes defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.. human defined as following: Members of the species Homo sapiens.. genome defined as following: Anatomical set of genes in all the chromosomes.. HAS defined as following: Bladder sphincter dysfunction in an individual with normal bladder innervation, which may lead to renal impairment.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. MSL complex defined as following: A histone acetyltransferase complex that catalyzes the acetylation of a histone H4 lysine residue at position 16. In human, it contains the catalytic subunit MOF, and MSL1, MSL2 and MSL3. [PMID:16227571, PMID:20018852]. X chromosome defined as following: The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species..", "label": "no"} {"id": "converted_3733", "sentence1": "Has saracatinib been tested in clinical trials?", "sentence2": "Saracatinib as a metastasis inhibitor in metastatic castration-resistant prostate cancer: A University of Chicago Phase 2 Consortium and DOD/PCF Prostate Cancer Clinical Trials Consortium Study., A phase II study of saracatinib (AZD0530), a Src inhibitor, administered orally daily to patients with advanced thymic malignancies., Phase II study of saracatinib (AZD0530) in patients with previously treated metastatic colorectal cancer., Metastatic colorectal cancer patients who had received one prior treatment and had measurable disease were enrolled in this phase 2 study., A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer's disease., Herein, we present a Phase Ib trial of the repurposed investigational drug AZD0530, a Src family kinase inhibitor specific for Fyn and Src kinase, for the treatment of patients with mild-to-moderate AD., The study was a 4-week Phase Ib multiple ascending dose, randomized, double-blind, placebo-controlled trial of AZD0530 in AD patients with Mini-Mental State Examination (MMSE) scores ranging from 16 to 26.[SEP]Relations: Saracatinib has relations: drug_drug with Ceritinib, drug_drug with Ceritinib, drug_drug with Ibrutinib, drug_drug with Ibrutinib, drug_drug with Crizotinib, drug_drug with Crizotinib, drug_drug with Cobimetinib, drug_drug with Cobimetinib, drug_drug with Erlotinib, drug_drug with Erlotinib. Definitions: Saracatinib defined as following: An orally available 5-, 7-substituted anilinoquinazoline with anti-invasive and anti-tumor activities. Saracatinib is a dual-specific inhibitor of Src and Abl, protein tyrosine kinases that are overexpressed in chronic myeloid leukemia cells. This agent binds to and inhibits these tyrosine kinases and affects cell motility, cell migration, adhesion, invasion, proliferation, differentiation, and survival. Specifically, Saracatinib inhibits Src kinase-mediated osteoclast bone resorption.. Src defined as following: Proto-oncogene tyrosine-protein kinase Src (536 aa, ~60 kDa) is encoded by the human SRC gene. This protein is involved in both receptor-mediated signal transduction and tyrosine phosphorylation.. Fyn defined as following: Tyrosine-protein kinase Fyn (537 aa, ~61 kDa) is encoded by the human FYN gene. This protein is involved in tyrosine phosphorylation, cytoskeleton remodeling and signal transduction.. Src kinase defined as following: A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.. Alzheimer's disease defined as following: Alzheimer's disease caused by mutation(s) in the APP gene, encoding amyloid-beta A4 protein. The onset of this condition typically occurs before age 65.. Prostate Cancer defined as following: A primary or metastatic malignant tumor involving the prostate gland. The vast majority are carcinomas.. saracatinib defined as following: An orally available 5-, 7-substituted anilinoquinazoline with anti-invasive and anti-tumor activities. Saracatinib is a dual-specific inhibitor of Src and Abl, protein tyrosine kinases that are overexpressed in chronic myeloid leukemia cells. This agent binds to and inhibits these tyrosine kinases and affects cell motility, cell migration, adhesion, invasion, proliferation, differentiation, and survival. Specifically, Saracatinib inhibits Src kinase-mediated osteoclast bone resorption..", "label": "yes"} {"id": "converted_2735", "sentence1": "Is Cystatin D a biomarker?", "sentence2": "Cystatin D (CST5): An ultra-early inflammatory biomarker of traumatic brain injury.[SEP]Relations: brain injury has relations: contraindication with Cyclopentolate, contraindication with Cyclopentolate, contraindication with Isopropamide, contraindication with Isopropamide, contraindication with Guaifenesin, contraindication with Guaifenesin, contraindication with Homatropine methylbromide, contraindication with Homatropine methylbromide, contraindication with Hydrocodone, contraindication with Hydrocodone. Definitions: traumatic brain injury defined as following: A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.. Cystatin D defined as following: This gene is involved in the inhibition of cathepsins in the oral cavity..", "label": "yes"} {"id": "converted_530", "sentence1": "Is there an association between bruxism and reflux", "sentence2": "Rhythmic masticatory muscle activity, including sleep bruxism (SB), can be induced in healthy individuals by experimental esophageal acidification, which plays an important role in the pathogenesis of gastroesophageal reflux disease (GERD). However, no robust evidence supports the association between SB and GERD., Sleep bruxism is prevalent in GERD patients, and GERD is highly associated with SB., Our large-scale cross-sectional study found that problem behaviors in adolescents were associated with sleep problems, including sleep bruxism, as well as lifestyle and food habits and GERD symptoms., The frequencies of EMG bursts, rhythmic masticatory muscle activity (RMMA) episodes, grinding noise, and the RMMA/microarousal ratio were significantly higher in the 20-minute period after acidic infusion than after saline infusion. RMMA episodes including SB were induced by esophageal acidification. , Direct restorative treatment of dental erosion caused by gastroesophageal reflux disease associated with bruxism:, This article presents a case report of a 27-year-old male smoker with tooth wear and dentin sensitivity caused by GERD associated with bruxism, Dental wear caused by association between bruxism and gastroesophageal reflux disease:, This paper presents a case report in which bruxism associated with acid feeding, smoking habit and episodes of gastric reflow caused severe tooth wear and great muscular discomfort with daily headache episodes., most jaw muscle activities, ie, RMMA, single short-burst, and clenching episodes, occur in relation to gastroesophageal reflux mainly in the supine position., Association between nocturnal bruxism and gastroesophageal reflux., Nocturnal bruxism may be secondary to nocturnal gastroesophageal reflux, occurring via sleep arousal and often together with swallowing.[SEP]Relations: Gastroesophageal reflux has relations: disease_phenotype_positive with Joubert syndrome with Jeune asphyxiating thoracic dystrophy, disease_phenotype_positive with Joubert syndrome with Jeune asphyxiating thoracic dystrophy, disease_phenotype_positive with citrullinemia, disease_phenotype_positive with citrullinemia, drug_effect with Febuxostat, drug_effect with Febuxostat. gastroesophageal reflux disease has relations: contraindication with Racementhol, contraindication with Racementhol, contraindication with Butabarbital, contraindication with Butabarbital. Definitions: gastroesophageal reflux defined as following: Effortless regurgitation of gastric contents that commonly occurs in infants, usually right after feeding or burping.. headache defined as following: The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.. Sleep bruxism defined as following: A sleep disorder characterized by grinding and clenching of the teeth and forceful lateral or protrusive jaw movements. Sleep bruxism may be associated with TOOTH INJURIES; TEMPOROMANDIBULAR JOINT DISORDERS; sleep disturbances; and other conditions.. tooth wear defined as following: Loss of the tooth substance by chemical or mechanical processes. muscular defined as following: One of the contractile organs of the body.. saline defined as following: A crystalloid solution that contains 9.0g of SODIUM CHLORIDE per liter of water. It has a variety of uses, including: as a CONTACT LENS SOLUTION, in OPHTHALMIC SOLUTIONS and NASAL LAVAGE, in wound irrigation, and for FLUID THERAPY.. gastroesophageal reflux disease defined as following: Retrograde flow of gastric juice (GASTRIC ACID) and/or duodenal contents (BILE ACIDS; PANCREATIC JUICE) into the distal ESOPHAGUS, commonly due to incompetence of the LOWER ESOPHAGEAL SPHINCTER.. bruxism defined as following: A disorder characterized by grinding and clenching of the teeth.. SB defined as following: A metallic element that has the atomic symbol Sb, atomic number 51, and atomic weight 121.75. It is used as a metal alloy and as medicinal and poisonous salts. It is toxic and an irritant to the skin and the mucous membranes.. acidic defined as following: Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. (Grant & Hackh's Chemical Dictionary, 5th ed). esophageal defined as following: Of or relating to the esophagus..", "label": "yes"} {"id": "converted_904", "sentence1": "Are there any desmins present in plants?", "sentence2": "Inherited mutations in the gene coding for the intermediate filament protein desmin have been demonstrated to cause severe skeletal and cardiac myopathies., Mutations in the intermediate filament (IF) protein desmin cause severe forms of myofibrillar myopathy characterized by partial aggregation of the extrasarcomeric desmin cytoskeleton and structural disorganization of myofibrils., The family of 70 intermediate filament genes (including those encoding keratins, desmins, and lamins) is now known to be associated with a wide range of diverse diseases, at least 72 distinct human pathologies, including skin blistering, muscular dystrophy, cardiomyopathy, premature aging syndromes, neurodegenerative disorders, and cataract. , Mutations in desmin have been associated with a subset of human myopathies., Characterization of a zebrafish (Danio rerio) desmin cDNA: an early molecular marker of myogenesis., Acute effects of desmin mutations on cytoskeletal and cellular integrity in cardiac myocytes., Desmin is a muscle-specific protein and a constitutive subunit of the intermediate filaments (IF) in skeletal, cardiac and smooth muscles. It is an early marker of skeletal muscle myogenesis. We have characterized a clone of desmin cDNA from an embryonic zebrafish (Danio rerio) cDNA library. , Immunohistochemical investigation showed a positive reaction for smooth muscle actin and desmins in the spindle cells proliferated in the lymph nodes; no cytokeratin positivity was detected. , We have raised monoclonal antibodies (Mab) to the Mr 55,000 desmin polypeptide, electrophoretically purified from cytoskeletal preparations of isolated bovine heart Purkinje fibers. , Mesothelial and ovarian carcinoma cells could not be distinguished by (intermediate) filament typing, using monoclonal antibodies (MAbs) to keratins, vimentins and desmins., A fast and convenient procedure for the purification of polymerization-competent smooth-muscle desmin is described. Desmin from chicken gizzard and hog stomach were compared by fingerprint techniques. [SEP]Relations: Protein S human has relations: drug_drug with Desmoteplase, drug_drug with Desmoteplase, drug_drug with Desirudin, drug_drug with Desirudin, drug_drug with Desogestrel, drug_drug with Desogestrel, drug_drug with Desvenlafaxine, drug_drug with Desvenlafaxine. smooth muscle tissue has relations: anatomy_protein_present with DESI2, anatomy_protein_present with DESI2. Definitions: zebrafish defined as following: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research.. cellular defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. myofibrils defined as following: The long cylindrical contractile organelles of STRIATED MUSCLE cells composed of ACTIN FILAMENTS; MYOSIN filaments; and other proteins organized in arrays of repeating units called SARCOMERES .. ovarian carcinoma defined as following: A primary or metastatic malignant neoplasm involving the ovary. Most primary malignant ovarian neoplasms are either carcinomas (serous, mucinous, or endometrioid adenocarcinomas) or malignant germ cell tumors. Metastatic malignant neoplasms to the ovary include carcinomas, lymphomas, and melanomas.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. keratins defined as following: A class of fibrous proteins or scleroproteins that represents the principal constituent of EPIDERMIS; HAIR; NAILS; horny tissues, and the organic matrix of tooth ENAMEL. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of TYPE I KERATIN and a TYPE II KERATIN, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. alpha-Keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to GENE DUPLICATION.. cataract defined as following: Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed). cardiomyopathy defined as following: A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).. desmin defined as following: Desmin (470 aa, ~54 kDa) is encoded by the human DES gene. This protein is involved in the regulation of cytoskeletal dynamics in muscle cells.. cardiac myocytes defined as following: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).. intermediate filaments defined as following: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus.. muscular dystrophy defined as following: A heterogeneous group of inherited MYOPATHIES, characterized by wasting and weakness of the SKELETAL MUSCLE. They are categorized by the sites of MUSCLE WEAKNESS; AGE OF ONSET; and INHERITANCE PATTERNS.. cytoskeletal defined as following: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.. monoclonal antibodies defined as following: Antibodies produced by a single clone of cells.. smooth muscles defined as following: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed). cDNA defined as following: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.. neurodegenerative disorders defined as following: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.. human defined as following: Members of the species Homo sapiens.. lamins defined as following: Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.. clone defined as following: A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed). plants defined as following: Multicellular, eukaryotic life forms of kingdom Plantae. Plants acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations. It is a non-taxonomical term most often referring to LAND PLANTS. In broad sense it includes RHODOPHYTA and GLAUCOPHYTA along with VIRIDIPLANTAE..", "label": "no"} {"id": "converted_2461", "sentence1": "Does Evolocumab improve cognitive function?", "sentence2": "Conclusions In a randomized trial involving patients who received either evolocumab or placebo in addition to statin therapy, no significant between-group difference in cognitive function was observed over a median of 19 months. , Results A total of 1204 patients were followed for a median of 19 months; the mean (±SD) change from baseline over time in the raw score for the spatial working memory strategy index of executive function (primary end point) was -0.21±2.62 in the evolocumab group and -0.29±2.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority). There were no significant between-group differences in the secondary end points of scores for working memory (change in raw score, -0.52 in the evolocumab group and -0.93 in the placebo group), episodic memory (change in raw score, -1.53 and -1.53, respectively), or psychomotor speed (change in raw score, 5.2 msec and 0.9 msec, respectively). , Conclusions In a randomized trial involving patients who received either evolocumab or placebo in addition to statin therapy, no significant between-group difference in cognitive function was observed over a median of 19 months., There were no significant between-group differences in the secondary end points of scores for working memory (change in raw score, -0.52 in the evolocumab group and -0.93 in the placebo group), episodic memory (change in raw score, -1.53 and -1.53, respectively), or psychomotor speed (change in raw score, 5.2 msec and 0.9 msec, respectively).[SEP]", "label": "no"} {"id": "converted_1826", "sentence1": "Is the protein lefty an inhibitor of nodal?", "sentence2": "The expression of lefty, an inhibitor of nodal is often reduced in tumor cells., Nodal, and an inhibitor, Lefty., as well as the expression of Lefty, an inhibitor of nodal signaling,, he Nodal inhibitor lefty, The morphogen Nodal was proposed to form a long-range signaling gradient via a reaction-diffusion system, on the basis of differential diffusion rates of Nodal and its antagonist Lefty.[SEP]Relations: malignancy in giant cell tumor of bone has relations: disease_disease with bone sarcoma, disease_disease with bone sarcoma, disease_disease with malignant giant cell tumor, disease_disease with malignant giant cell tumor. Definitions: tumor cells defined as following: Cells of, or derived from, a tumor.. Nodal defined as following: Nodal homolog (347 aa, ~40 kDa) is encoded by the human NODAL gene. This protein is involved in mesoderm formation and axial patterning..", "label": "yes"} {"id": "converted_108", "sentence1": "Are stress granules involved in the pathogenesis of Amyotrophic Lateral Sclerosis?", "sentence2": "SGs have been linked to several pathologies including inflammatory diseases, cancer, viral infection, and neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)., Like several other ALS-associated proteins, CREST is recruited to induced stress granules., Our data indicate that CREST and certain other ALS-linked proteins share several features implicated in ALS pathogenesis, namely the ability to aggregate, be recruited to stress granules and alter paraspeckle integrity., A unifying feature of many proteins associated with ALS, including TDP-43 and ataxin-2, is that they localize to stress granules. , Two RNA-binding proteins, TDP-43 and FUS, aggregate in the degenerating motor neurons of ALS patients, and mutations in the genes encoding these proteins cause some forms of ALS., Recent work connecting TDP-43 and FUS to stress granules has suggested how this cellular pathway, which involves protein aggregation as part of its normal function, might be coopted during disease pathogenesis., Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress. Since only the mutants, but not the endogenous wild-type FUS, are associated with stress granules under most of the stress conditions reported to date, the relationship between FUS and stress granules represents a mutant-specific phenotype and thus may be of significance in mutant-induced pathogenesis., Fused in sarcoma (FUS) belongs to the group of RNA-binding proteins implicated as underlying factors in amyotrophic lateral sclerosis (ALS) and certain other neurodegenerative diseases. Multiple FUS gene mutations have been linked to hereditary forms, and aggregation of FUS protein is believed to play an important role in pathogenesis of these diseases. In cultured cells, FUS variants with disease-associated amino acid substitutions or short deletions affecting nuclear localization signal (NLS) and causing cytoplasmic mislocalization can be sequestered into stress granules (SGs)., Profilin 1 associates with stress granules and ALS-linked mutations alter stress granule dynamics, Here we report that profilin 1 and related protein profilin 2 are novel stress granule-associated proteins in mouse primary cortical neurons and in human cell lines and that ALS-linked mutations in profilin 1 alter stress granule dynamics, providing further evidence for the potential role of stress granules in ALS pathogenesis, Furthermore, in response to oxidative stress or heat shock conditions in cultures and in vivo, the ALS-linked FUS mutants, but not wild-type FUS, assembled into perinuclear stress granules in proportion to their cytoplasmic expression levels., Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules., Our results suggest that the ALS mutations in FUS NLS can impair FUS nuclear localization, induce cytoplasmic inclusions and stress granules, and potentially perturb RNA metabolism., RNA-binding ability of FUS regulates neurodegeneration, cytoplasmic mislocalization and incorporation into stress granules associated with FUS carrying ALS-linked mutations., TDP-43 is an RNA-binding protein linked to amyotrophic lateral sclerosis (ALS) that is known to regulate the splicing, transport, and storage of specific mRNAs into stress granules, In amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration, TAR DNA binding protein 43 (TDP-43) accumulates in the cytoplasm of affected neurons and glia, where it associates with stress granules (SGs) and forms large inclusions, Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress, Mutant FUS proteins that cause amyotrophic lateral sclerosis incorporate into stress granules, Mutations in Fus cause amyotrophic lateral sclerosis (ALS) and the mutant protein forms inclusions that appear to correspond to stress granules, Recent work also suggests that TDP-43 associates with cytoplasmic stress granules, which are transient structures that form in response to stress. , We found that in response to oxidative stress and to environmental insults of different types TDP-43 is capable to assemble into stress granules (SGs), ribonucleoprotein complexes where protein synthesis is temporarily arrested. , Moreover, proteins known to be stress granule markers co-deposit with inclusions in fALS and FTLD-FUS patients, implicating stress granule formation in the pathogenesis of these diseases. We propose that two pathological hits, namely nuclear import defects and cellular stress, are involved in the pathogenesis of FUS-opathies., Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress., Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics., Moreover, proteins known to be stress granule markers co-deposit with inclusions in fALS and FTLD-FUS patients, implicating stress granule formation in the pathogenesis of these diseases. We propose that two pathological hits, namely nuclear import defects and cellular stress, are involved in the pathogenesis of FUS-opathies. ., Autophagy regulates amyotrophic lateral sclerosis-linked fused in sarcoma-positive stress granules in neurons, However, the role of autophagy in regulation of FUS-positive stress granules (SGs) and aggregates remains unclear. , Although co-localized primarily in the nucleus in normal condition, FUS/TLS and PRMT1 were partially recruited to the cytoplasmic granules under oxidative stress, which were merged with stress granules (SGs) markers in SH-SY5Y cell., The effect of PRMT1-mediated arginine methylation on the subcellular localization, stress granules, and detergent-insoluble aggregates of FUS/TLS, Stress granules are cytoplasmic inclusions that repress translation of a subset of RNAs in times of cellular stress, and several proteins implicated in neurodegeneration (i.e. Ataxin-2 and SMN) interact with stress granules, These findings support a two-hit hypothesis, whereby cytoplasmic mislocalization of FUS protein, followed by cellular stress, contributes to the formation of cytoplasmic aggregates that may sequester FUS, disrupt RNA processing and initiate motor neuron degeneration., Here, we exploited a Drosophila model of ALS and neuronal cell lines to elucidate the role of the RNA-binding ability of FUS in regulating FUS-mediated toxicity, cytoplasmic mislocalization and incorporation into stress granules (SGs). , Stress granules as crucibles of ALS pathogenesis[SEP]Relations: amyotrophic lateral sclerosis has relations: disease_protein with GLE1, disease_protein with GLE1, disease_protein with FOS, disease_protein with FOS, disease_protein with PPARGC1A, disease_protein with PPARGC1A, disease_protein with ANG, disease_protein with ANG, disease_protein with INA, disease_protein with INA. Definitions: amyotrophic lateral sclerosis defined as following: A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94). cancer defined as following: A malignant tumor at the original site of growth.. SGs defined as following: A rare, autosomal dominant inherited syndrome often caused by mutations in the SKI gene. It is characterized by premature fusion of skull bones and distinctive facial features, including a long, narrow head, hypertelorism, exophthalmos, downslanting palpebral fissures, a high, narrow palate, micrognathia, and low-set ears. The bodies of affected individuals resemble those of people with Marfan syndrome.. profilin 1 defined as following: This gene plays a role in the regulation of actin polymerization.. mutant protein defined as following: A protein with an amino acid sequence that differs from the wildtype, canonical sequence.. TDP-43 defined as following: TAR DNA-binding protein 43 (414 aa, ~45 kDa) is encoded by the human TARDBP gene. This protein is involved in the regulation of both transcription and mRNA splicing.. SMN defined as following: Small nuclear ribonucleoprotein-associated protein N (240 aa, ~25 kDa) is a nucleotide metabolism protein that is encoded by the human SNRPN gene and plays a role in mRNA splicing.. liposarcoma defined as following: A malignant tumor derived from primitive or embryonal lipoblastic cells. It may be composed of well-differentiated fat cells or may be dedifferentiated: myxoid (LIPOSARCOMA, MYXOID), round-celled, or pleomorphic, usually in association with a rich network of capillaries. Recurrences are common and dedifferentiated liposarcomas metastasize to the lungs or serosal surfaces. (From Dorland, 27th ed; Stedman, 25th ed). glia defined as following: The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear.. cytoplasmic granules defined as following: Condensed areas of cellular material that may be bounded by a membrane.. RNAs defined as following: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed). CREST defined as following: A mild form of LIMITED SCLERODERMA, a multi-system disorder. Its features include symptoms of CALCINOSIS; RAYNAUD DISEASE; ESOPHAGEAL MOTILITY DISORDERS; sclerodactyly, and TELANGIECTASIS. When the defect in esophageal function is not prominent, it is known as CRST syndrome.. stress granules defined as following: A dense aggregation in the cytosol composed of proteins and RNAs that appear when the cell is under stress. [GOC:ans, PMID:17284590, PMID:17601829, PMID:17967451, PMID:20368989]. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. FTD defined as following: The most common clinical form of FRONTOTEMPORAL LOBAR DEGENERATION, this dementia presents with personality and behavioral changes often associated with disinhibition, apathy, and lack of insight.. cultured cells defined as following: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.. Ataxin-2 defined as following: A Poly(A) RNA-binding protein that negatively regulates EGFR ENDOCYTOSIS. An increased risk for developing AMYOTROPHIC LATERAL SCLEROSIS 13 is observed in patients who have more than 23 CAG repeats in the ATXN2 gene coding sequence. Larger CAG expansions in the ATXN2 gene occur in SPINOCEREBELLAR ATAXIA 2 patients.. PRMT1 defined as following: Protein arginine N-methyltransferase 1 (361 aa, ~42 kDa) is encoded by the human PRMT1 gene. This protein plays a role in the methylation of the guanidino nitrogens of arginyl residues in substrate proteins.. frontotemporal lobar degeneration defined as following: Heterogeneous group of neurodegenerative disorders characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Multiple subtypes or forms are recognized based on presence or absence of TAU PROTEIN inclusions. FTLD includes three clinical syndromes: FRONTOTEMPORAL DEMENTIA, semantic dementia, and PRIMARY PROGRESSIVE NONFLUENT APHASIA.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. cytoplasm defined as following: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990). mutants defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. paraspeckle defined as following: Discrete subnuclear bodies in the interchromatin nucleoplasmic space, often located adjacent to nuclear specks. 10-20 paraspeckles are typically found in human cell nuclei. [GOC:jl, PMID:11790299]. FUS protein defined as following: A multifunctional heterogeneous-nuclear ribonucleoprotein that may play a role in homologous DNA pairing and recombination. The N-terminal portion of protein is a potent transcriptional activator, while the C terminus is required for RNA binding. The name FUS refers to the fact that genetic recombination events result in fusion oncogene proteins (ONCOGENE PROTEINS, FUSION) that contain the N-terminal region of this protein. These fusion proteins have been found in myxoid liposarcoma (LIPOSARCOMA, MYXOID) and acute myeloid leukemia.. RNA-binding proteins defined as following: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.. viral infection defined as following: A general term for diseases caused by viruses.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. inclusions defined as following: A generic term for any circumscribed mass of foreign (e.g., lead or viruses) or metabolically inactive materials (e.g., ceroid or MALLORY BODIES), within the cytoplasm or nucleus of a cell. Inclusion bodies are in cells infected with certain filtrable viruses, observed especially in nerve, epithelial, or endothelial cells. (Stedman, 25th ed). nucleus defined as following: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). neurodegeneration defined as following: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.. motor neuron defined as following: Neurons which activate MUSCLE CELLS.. NLS defined as following: An amino acid sequence that directs the post-translational transport of a protein to the nucleus. The sequence contains positively charged amino acids such as arginine and lysine.. neurodegenerative diseases defined as following: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures..", "label": "yes"} {"id": "converted_1467", "sentence1": "Are BRAF mutations common in melanoma?", "sentence2": "patients with BRAF-mutant melanoma., BRAF-mutated melanoma , The RAS/RAF/MEK/ERK pathway has been reported to be activated in over 80% of all cutaneous melanomas, making it the focus of many scientific studies in the melanoma field. Discoveries of mutations and aberrant expression of components in this cascade, in particular, BRAF and NRAS render a deeper understanding of the mechanisms responsible for oncogenesis and provide new therapeutic strategies for this deadly disease. , BRAF-targeted therapies (e.g., vemurafenib, dabrafenib) have showed impressive results in systemic therapy for melanoma harboring activating BRAF V600E mutations. , An independent cohort of 91 archival MUPs was also screened for 46 hot spot mutations highly prevalent in melanoma including BRAF, NRAS, KIT, GNAQ, and GNA11., a high rate of BRAF (45 of 101, 45%) and NRAS (32 of 101, 32%) mutations, collectively indicating a mutation profile consistent with cutaneous sun-exposed melanomas., Treatment of advanced melanoma has been improved with the advent of the BRAF inhibitors., BRAF is the most prevalent oncogene and an important therapeutic target in melanoma., Activating BRAF mutations, leading to constitutive activation of the MAPK signaling pathway, are common in a variety of human cancers. Several small molecule BRAF inhibitors have been developed during the last years and shown promising results in clinical trials, especially for metastatic melanoma, while they have been less effective in colon cancer. , BRAF mutations have emerged as an important predictive biomarker for metastasized melanoma. , BRAF V600 selective inhibitors have been approved for the treatment of V600 mutation positive metastatic melanoma, , BRAF(V600) mutation-positive melanoma , Melanoma is the most aggressive form of skin cancer. The treatment of patients with advanced melanoma is rapidly evolving due to an improved understanding of molecular drivers of this disease. Somatic mutations in BRAF are the most common genetic alteration found in these tumors., genetically activated BRAF, is now commonly prescribed for metastatic melanoma harboring a BRAF mutation., BRAF inhibitors improve melanoma patient survival, but resistance invariably develops. , BRAF inhibitors elicit rapid antitumor responses in the majority of patients with BRAF(V600)-mutant melanoma, but acquired drug resistance is almost universal. , Most patients with BRAF(V600)-mutant metastatic melanoma develop resistance to selective RAF kinase inhibitors. , BRAF(V600E) mutation confers constitutive BRAK kinase activation in melanoma cells, promoting tumor growth. This discovery led to the development of BRAF kinase inhibitors like vemurafenib and dabrafenib. , (V600)BRAF mutation was identified as an ideal target for clinical therapy due to its indispensable roles in supporting melanoma initiation and progression., The Braf(V600E) mutation has been detected in patients with metastatic melanoma, colon, thyroid, and other cancers., Since the identification of activating BRAF mutations and subsequent development of drugs targeting the mutant BRAF protein, oncologists now need to incorporate prognostic and predictive biomarkers into treatment decisions for their melanoma patient, BRAF mutations occur in approximately 8% of all human cancers and approach 50% in melanoma and papillary carcinoma of thyroid., Vemurafenib is a selective and potent small molecule inhibitor of the V600 mutant form of the BRAF protein used in the treatment of melanoma and colorectal cancer., Molecular studies demonstrated that the melanoma was positive for the 1799T>A (V600E) mutation in the BRAF gene., RAF kinase inhibitors have substantial therapeutic effects in patients with BRAF-mutant melanoma., An activating BRAF (V600E) kinase mutation occurs in approximately half of melanomas. , Activating mutations in the BRAF gene occur in approximately 50% of melanomas. More than 70% of BRAF mutations are V600E and 10-30% are V600K., Activating BRAF mutations, leading to constitutive activation of the MAPK signaling pathway, are common in a variety of human cancers., Several small molecule BRAF inhibitors have been developed during the last years and shown promising results in clinical trials, especially for metastatic melanoma, while they have been less effective in colon cancer. , Personalized melanoma medicine has progressed from histopathologic features to serum markers to molecular profiles. Since the identification of activating BRAF mutations and subsequent development of drugs targeting the mutant BRAF protein, oncologists now need to incorporate prognostic and predictive biomarkers into treatment decisions for their melanoma patients., The clinical activity of BRAF inhibitor (BRAF-I) therapy is a major breakthrough in the treatment of metastatic melanoma carrying BRAF mutations. , The discovery of BRAF mutations in melanoma led to the development of BRAF inhibitors for the treatment of advanced melanoma. , BRAF represents one of the most frequently mutated protein kinase genes in human tumours. The mutation is commonly tested in pathology practice. BRAF mutation is seen in melanoma, papillary thyroid carcinoma (including papillary thyroid carcinoma arising from ovarian teratoma), ovarian serous tumours, colorectal carcinoma, gliomas, hepatobiliary carcinomas and hairy cell leukaemia., Indeed, recent clinical trials involving BRAF selective inhibitors exhibited promising response rates in metastatic melanoma patients. , A majority of cutaneous melanomas show activating mutations in the NRAS or BRAF proto-oncogenes, components of the Ras-Raf-Mek-Erk (MAPK) signal transduction pathway. The discovery of activating BRAF mutations in ∼50% of all melanomas has proved to be a turning point in the therapeutic management of the disseminated disease. This review summarizes the critical role of BRAF in melanoma pathophysiology, the clinical and pathological determinants of BRAF mutation status and finally addresses the current state of the art of BRAF inhibitors., To better understand the BRAF mutation profile in melanomas, we retrospectively analyzed data from 1112 primary and metastatic melanomas at our institution. The cohort included nonacral cutaneous (n = 774), acral (n = 111), mucosal (n = 26), uveal (n = 23), leptomeningeal (n = 1), and metastatic melanomas of unknown primary site (n = 177). BRAF mutation hotspot regions in exons 11 and 15 were analyzed by pyrosequencing or with the primer extension MassARRAY system. A total of 499 (44.9%) specimens exhibited BRAF mutations, involving exon 15 [497 (99.6%)] or exon 11 [2 (0.4%)]. p.V600E was detected in 376 (75.4%) cases; the remaining 123 (24.6%) cases exhibited non-p.V600E mutations, of which p.V600K was most frequent [86 (17.2%)]. BRAF mutations were more frequent in nonacral cutaneous (51.4%) than acral melanomas [18 (16.2%)] (P < 0.001); however, there was no significant difference among cutaneous histological subtypes. All mucosal, uveal, and leptomeningeal melanomas were BRAF wild type (WT)., Recently, it was reported that BRAF mutations are frequent in melanoma., Activating mutations in BRAF are the most common genetic alterations in melanoma., Oncogenic BRAF and NRAS mutations are frequent in malignant melanoma., Mutation of BRAF is now known to be common in cutaneous melanomas, and raises possible new therapeutic options of anti-RAF treatment for these patients, BRAF mutations are common events in a variety of melanocytic nevi and primary cutaneous melanomas, Approximately 40-60% of melanomas from Caucasian populations carry activating mutations in the BRAF oncogene, with the most common being the p.Val600Glu (V600E) hotspot mutation in exon 15, Using a cohort of 115 patients with primary invasive melanomas, we show that BRAF mutations are statistically significantly more common in melanomas occurring on skin subject to intermittent sun exposure than elsewhere (23 of 43 patients; P<.001, two-sided Fisher's exact test), BRAF mutations have been identified as the most common oncogene mutation in melanomas, especially important in those originating on nonchronically sun-damaged skin. [SEP]Relations: melanoma has relations: disease_protein with BRAF, disease_protein with BRAF, disease_protein with TNF, disease_protein with TNF, disease_protein with ASF1A, disease_protein with ASF1A. colorectal carcinoma has relations: disease_protein with BRAF, disease_protein with BRAF. malignant colon neoplasm has relations: disease_protein with BRAF, disease_protein with BRAF. Definitions: Vemurafenib defined as following: An orally bioavailable, ATP-competitive, small-molecule inhibitor of BRAF(V600E) kinase with potential antineoplastic activity. Vemurafenib selectively binds to the ATP-binding site of BRAF(V600E) kinase and inhibits its activity, which may result in an inhibition of an over-activated MAPK signaling pathway downstream in BRAF(V600E) kinase-expressing tumor cells and a reduction in tumor cell proliferation. Approximately 90% of BRAF gene mutations involve a valine-to-glutamic acid mutation at residue 600 (V600E); the oncogene protein product, BRAF(V600E) kinase, exhibits a markedly elevated activity that over-activates the MAPK signaling pathway. The BRAF(V600E) gene mutation has been found to occur in approximately 60% of melanomas, and in about 8% of all solid tumors, including melanoma, colorectal, thyroid and other cancers.. skin cancer defined as following: A primary or metastatic malignant neoplasm involving the skin. Primary malignant skin neoplasms most often are carcinomas (either basal cell or squamous cell carcinomas) or melanomas. Metastatic malignant neoplasms to the skin include carcinomas and lymphomas.. malignant melanoma defined as following: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445). melanocytic nevi defined as following: A nevus characterised by the presence of excessive pigment.. colon cancer defined as following: A primary or metastatic malignant neoplasm that affects the colon. Representative examples include carcinoma, lymphoma, and sarcoma.. BRAF defined as following: Serine/threonine-protein kinase B-raf (766 aa, ~84 kDa) is encoded by the human BRAF gene. This protein plays a role in protein phosphorylation, mitogenesis and neuronal signal transduction.. BRAK defined as following: This gene is involved in cellular homeostasis and chemotaxis.. gliomas defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21). cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. NRAS defined as following: Human Oncogene N-RAS is a mutated variant of NRAS Gene (RAS Family), which encodes p21 N-Ras Protein, a monomeric GTPase involved in transmembrane signal transduction that alternates between inactive GDP-bound and active GTP-bound forms. RAS is activated by a guanine nucleotide-exchange factor and inactivated by a GTPase-activating protein. Mitogen-stimulated RAS stabilizes MYC protein and enhances MYC accumulation by the RAS/RAF/MAPK pathway, which appears to inhibit the proteasome-dependent degradation of MYC. Implicated in a variety of human tumors, specific amino acid mutations activate c-RAS and transform cells. Oncogene NRAS disrupts normal cell function.. BRAF gene defined as following: This gene is involved in cell organization/biogenesis and the inhibition of apoptosis.. Melanoma defined as following: A benign or malignant, primary or metastatic neoplasm affecting the melanocytes.. GNAQ defined as following: Guanine nucleotide-binding protein G(q) subunit alpha (353 aa, ~41 kDa) is encoded by the human GNAQ gene. This protein may play a role in transduction and modulation of various transmembrane signaling systems.. acral defined as following: Applies to an abnormality that affects the distal portions of limbs (hand, foot) and head (ears, nose). []. colorectal carcinoma defined as following: A malignant epithelial neoplasm that arises from the colon or rectum and invades through the muscularis mucosa into the submucosa. The vast majority are adenocarcinomas.. KIT defined as following: Combining with stem cell factor (SCF) receptor ligand and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity by catalysis of the reaction: ATP + a protein-L-tyrosine = ADP + a protein-L-tyrosine phosphate. Stem cell factor is a cytokine that stimulates mast cell growth and differentiation. [GOC:jl, GOC:signaling, PMID:10698217]. ovarian teratoma defined as following: A benign, immature, or malignant teratoma arising from the ovary.. dabrafenib defined as following: An orally bioavailable inhibitor of B-raf (BRAF) protein with potential antineoplastic activity. Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. B-raf belongs to the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations.. papillary thyroid carcinoma defined as following: A differentiated adenocarcinoma arising from the follicular cells of the thyroid gland. Radiation exposure is a risk factor and it is the most common malignant thyroid lesion, comprising 75% to 80% of all thyroid cancers in iodine sufficient countries. Diagnostic procedures include thyroid ultrasound and fine needle biopsy. Microscopically, the diagnosis is based on the distinct characteristics of the malignant cells, which include enlargement, oval shape, elongation, and overlapping of the nuclei. The nuclei also display clearing or have a ground glass appearance.. metastatic melanoma defined as following: A melanoma that has spread from its primary site to another anatomic site. Melanomas frequently metastasize to lymph nodes, liver, lungs, and brain.. hairy cell defined as following: An abnormal large leukocyte found in the blood in hairy cell leukemia; it has numerous irregular cytoplasmic villi that give it a flagellated or hairy appearance.. BRAF kinase defined as following: A raf kinase subclass found at high levels in neuronal tissue. The B-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. oncogene defined as following: Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of \"v-\" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix \"c-\" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. genetic alterations defined as following: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.. GNA11 defined as following: Guanine nucleotide-binding protein subunit alpha-11 (359 aa, ~42 kDa) is encoded by the human GNA11 gene. This protein is involved in the activation of phospholipase C.. human defined as following: Members of the species Homo sapiens.. uveal defined as following: The pigmented vascular coat of the eyeball, consisting of the CHOROID; CILIARY BODY; and IRIS, which are continuous with each other. (Cline et al., Dictionary of Visual Science, 4th ed). WT defined as following: A designation used to describe a wild-type zebrafish line that is of unknown stock.. melanoma defined as following: A benign or malignant, primary or metastatic neoplasm affecting the melanocytes..", "label": "yes"} {"id": "converted_2616", "sentence1": "Is Tocilizumab effective for Giant-Cell Arteritis?", "sentence2": "Emerging evidence for adjunctive therapy with tocilizumab, methotrexate, aspirin, angiotensin receptor blockers, and statins is encouraging and may lead to a more mainstream role for these therapies among patients with GCA., TNF-α blockers are ineffective in giant cell arteritis, while observational evidence and a phase 2 randomized trial support the use of tocilizumab in relapsing giant cell arteritis. , OBJECTIVES: Randomised-controlled trials have recently proven the efficacy of the interleukin (IL)-6 receptor antagonist tocilizumab (TCZ) in giant cell arteritis (GCA). , CONCLUSIONS: TCZ may exert its therapeutic effects in GCA by increasing the proliferation and activation of Tregs, and by reverting the pathogenic Treg phenotype seen during active disease., Cyclophosphamide and tocilizumab look promising but require validation in further studies. , Therefore, tocilizumab (humanised monoclonal antibody binding the human interleukin-6 receptor) was introduced as a potential salvage therapy with a swift consecutive resolution of the systemic symptoms and stabilization of the ophthalmic lesions.CONCLUSIONS: Although a late effect of steroids pulses cannot be formally ruled out in this dramatic situation, tocilizumab likely offered a decisive effect in preventing bilateral blindness and may have contributed to steroid tapering. Tocilizumab may represent a new early effective second-line treatment option in corticosteroid-resistant anterior ischemic optic neuropathy. , Tocilizumab for giant cell arteritis with corticosteroid-resistant progressive anterior ischemic optic neuropathy., CONCLUSIONS: Tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with giant-cell arteritis. Longer follow-up is necessary to determine the durability of remission and safety of tocilizumab., Two RCTs have evidenced the efficacy of tocilizumab in addition to glucocorticoids (GCs) in the treatment of giant cell arteritis (GCA)., Recent randomized placebo-controlled trials have reported on the efficacy and safety of abatacept and mostly tocilizumab in inducing and maintaining remission of GCA. , If a biological therapy is indicated, and in light of the data discussed in this review, the first choice would be tocilizumab in GCA and anti-TNF-α agents (mainly infliximab) in TAK., CONCLUSION: TCZ is effective in GCA., TNF-α blockers are ineffective in giant cell arteritis, while observational evidence and a phase 2 randomized trial support the use of tocilizumab in relapsing giant cell arteritis., A favorable outcome was rapidly observed both on clinical and biological data allowing a corticoid therapy sparing.Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. Primary liver cancer starts in the liver. Metastatic liver cancer starts somewhere else and spreads to your liver.
Risk factors for primary liver cancer include
Symptoms can include a lump or pain on the right side of your abdomen and yellowing of the skin. However, you may not have symptoms until the cancer is advanced. This makes it harder to treat. Doctors use tests that examine the liver and the blood to diagnose liver cancer. Treatment options include surgery, radiation, chemotherapy, or liver transplantation.
NIH: National Cancer Institute
. renal cell cancer defined as following: Primary or metastatic malignant neoplasm involving the kidney.. hypertension defined as following: Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.. Hepatocellular Carcinoma defined as following: A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.. sorafenib defined as following: A synthetic compound targeting growth signaling and angiogenesis. Sorafenib blocks the enzyme RAF kinase, a critical component of the RAF/MEK/ERK signaling pathway that controls cell division and proliferation; in addition, sorafenib inhibits the VEGFR-2/PDGFR-beta signaling cascade, thereby blocking tumor angiogenesis.. regorafenib defined as following: The anhydrous form of regorafenib, an orally bioavailable small molecule with potential antiangiogenic and antineoplastic activities. Regorafenib binds to and inhibits vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. VEGFRs are receptor tyrosine kinases that play important roles in tumor angiogenesis; the receptor tyrosine kinases RET, KIT, and PDGFR, and the serine/threonine-specific Raf kinase are involved in tumor cell signaling.. AXL defined as following: Tyrosine-protein kinase receptor UFO (894 aa, ~98 kDa) is encoded by the human AXL gene. This protein plays a role in ligand binding, signaling and cellular growth and differentiation.. thyroid cancer defined as following: A primary or metastatic malignant neoplasm affecting the thyroid gland.. palmar-plantar erythrodysesthesia defined as following: Chemotherapy-induced dermal side effects that are associated with the use of various CYTOSTATIC AGENTS. Symptoms range from mild ERYTHEMA and/or PARESTHESIA to severe ulcerative dermatitis with debilitating pain involving typically palmoplantar and intertriginous areas. These cutaneous manifestations are sometimes accompanied by nail anomalies.. diarrhea defined as following: An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.. nivolumab defined as following: A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Upon administration, nivolumab binds to and blocks the activation of PD-1, an immunoglobulin superfamily (IgSF) transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). This results in the activation of T-cells and cell-mediated immune responses against tumor cells. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity.. fatigue defined as following: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.. advanced hepatocellular carcinoma defined as following: Hepatocellular carcinoma that has spread extensively to other anatomic sites or is no longer responding to treatment.. lenvatinib defined as following: A synthetic, orally available inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR/FLK-1) tyrosine kinase with potential antineoplastic activity. Lenvatinib blocks VEGFR2 activation by VEGF, resulting in inhibition of the VEGF receptor signal transduction pathway, decreased vascular endothelial cell migration and proliferation, and vascular endothelial cell apoptosis.. tivantinib defined as following: An orally bioavailable small molecule inhibitor of c-Met with potential antineoplastic activity. c-Met inhibitor ARQ 197 binds to the c-Met protein and disrupts c-Met signal transduction pathways, which may induce cell death in tumor cells overexpressing c-Met protein or expressing constitutively activated c-Met protein. c-Met protein, the product of the proto-oncogene c-Met, is a receptor tyrosine kinase also known as hepatocyte growth factor receptor (HGFR); this protein is overexpressed or mutated in many tumor cell types and plays key roles in tumor cell proliferation, survival, invasion, and metastasis, and tumor angiogenesis.. foretinib defined as following: An orally bioavailable small molecule with potential antineoplastic activity. Foretinib binds to and selectively inhibits hepatocyte growth factor (HGF) receptor c-MET and vascular endothelial growth factor receptor 2 (VEGFR2), which may result in the inhibition of tumor angiogenesis, tumor cell proliferation and metastasis. The proto-oncogene c-MET has been found to be over-expressed in a variety of cancers. VEGFR2 is found on endothelial and hematopoietic cells and mediates the development of the vasculature and hematopoietic cells through VEGF signaling.. MET defined as following: Human MET wild-type allele is located within 7q31 and is approximately 126 kb in length. This allele, which encodes hepatocyte growth factor receptor protein, plays a role in the regulation of cellular tyrosine-kinase activity. Mutations in the MET gene are associated with papillary renal carcinoma.. cabozantinib defined as following: An orally bioavailable, small molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Cabozantinib strongly binds to and inhibits several RTKs, which are often overexpressed in a variety of cancer cell types, including hepatocyte growth factor receptor (MET), RET (rearranged during transfection), vascular endothelial growth factor receptor types 1 (VEGFR-1), 2 (VEGFR-2), and 3 (VEGFR-3), mast/stem cell growth factor (KIT), FMS-like tyrosine kinase 3 (FLT-3), TIE-2 (TEK tyrosine kinase, endothelial), tropomyosin-related kinase B (TRKB) and AXL. This may result in an inhibition of both tumor growth and angiogenesis, and eventually lead to tumor regression..", "label": "yes"} {"id": "converted_1594", "sentence1": "Is Tuberous Sclerosis a genetic disease?", "sentence2": "Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous sclerosis is a rare genetic disease, Tuberous sclerosis complex (TSC) is a multisystem genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, The disease is caused by mutational inactivation of the tumor suppressor gene tuberous sclerosis complex 1 (TSC1) or TSC2., mTOR inhibitors have antiepileptogenic and antiseizure effects in animal models of the genetic disease, tuberous sclerosis complex., Tuberous sclerosis (TSC) is an autosomal-dominant genetic disease, Tuberous sclerosis is a rare genetic disease, Tuberous Sclerosis Complex (TSC) is a genetic disease, Tuberous sclerosis complex (TSC) is a multiorgan genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous Sclerosis Complex (TSC) is a multiorgan genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous sclerosis complex (TSC) is a multiorgan genetic disease, In all these lesions, genetic alterations related to the tuberous sclerosis complex (TSC) have been demonstrated., Although epilepsy affects most patients with tuberous sclerosis complex (TSC), little is known about the natural history of epilepsy in this genetic disease., The tuberous sclerosis gene 2 product tuberin is an important regulator of the mammalian target of rapamycin (mTOR)., Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous Sclerosis Complex (TSC) is a multiorgan genetic disease, Tuberous sclerosis complex (TSC) is a relatively rare autosomal dominant disorder, Tuberous sclerosis is a genetic disease with autosomal dominant inheritance,, PEComas are related to the genetic alterations of tuberous sclerosis complex (TSC), an autosomal dominant genetic disease due to losses of TSC1 (9q34) or TSC2 (16p13.3) genes which seem to have a role in the regulation of the Rheb/mTOR/p70S6K pathway., Tuberous sclerosis complex (TSC) is a multiorgan genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous sclerosis is a rare genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease, Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either TSC1 or TSC2., Tuberous sclerosis complex (TSC) is a genetic disease caused by mutations in either TSC1 or TSC2 tumor suppressor genes., Mutation in either the TSC1 or TSC2 tumor suppressor gene is responsible for the inherited genetic disease of tuberous sclerosis complex., Tuberous sclerosis (TSC) is a frequent autosomal-dominant condition (affecting 1 in 6000 individuals) caused by various mutations in either the hamartin (TSC1) or the tuberin gene (TSC2)., Tuberous sclerosis is a rare genetic disease, Tuberous sclerosis (TS) is a genetic disease with prominent cutaneous and brain involvement , TSC was recognized to be a genetic disease with autosomal dominant inheritance, On average TSC families are very small; in most cases there are fewer than two informative meioses. The size distribution of chromosome 9 linked families was similar to that of non-linked families., The effects of missense changes and small in-frame deletions and insertions on protein function are not easy to predict, and the identification of such variants in individuals at risk of a genetic disease can complicate genetic counselling. One option is to perform functional tests to assess whether the variants affect protein function. We have used this strategy to characterize variants identified in the TSC1 and TSC2 genes in individuals with, or suspected of having, Tuberous Sclerosis Complex (TSC)., Tuberous sclerosis is a dominant hereditary disease, Many of these advances originated from studies of the genetic disease tuberous sclerosis complex (TSC)[SEP]Relations: tuberous sclerosis has relations: disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with genetic nervous system disorder, disease_disease with inherited neurodegenerative disorder, disease_disease with inherited neurodegenerative disorder. Definitions: tuberous sclerosis complex defined as following: Autosomal dominant neurocutaneous syndrome classically characterized by MENTAL RETARDATION; EPILEPSY; and skin lesions (e.g., adenoma sebaceum and hypomelanotic macules). There is, however, considerable heterogeneity in the neurologic manifestations. It is also associated with cortical tuber and HAMARTOMAS formation throughout the body, especially the heart, kidneys, and eyes. Mutations in two loci TSC1 and TSC2 that encode hamartin and tuberin, respectively, are associated with the disease.. autosomal dominant inheritance defined as following: A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. [HPO:curators]. epilepsy defined as following: A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313). disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. Tuberous sclerosis complex defined as following: A protein complex consisting of at least tumerin and hamartin; its formation may regulate hamartin homomultimer formation. The complex acts as a GTPase activating protein (GAP) for the small GTPase (Rheb), and inhibits the TOR signaling pathway. [PMID:10585443, PMID:17121544, PMID:9580671]. mTOR defined as following: Serine/threonine-protein kinase mTOR (2549 aa, ~289 kDa) is encoded by the human MTOR gene. This protein is involved in protein phosphorylation, signaling and cell growth.. 9q34 defined as following: A chromosome band present on 9q. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. autosomal defined as following: Any chromosome other than a sex chromosome. [GOC:mah]. PEComas defined as following: A family of mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. These cells do not have a normal anatomic homolog. (From Fletcher CDM, et. al., World Health Organization Classification of Tumors: Pathology and Genetics of Tumors of Soft Tissue and Bone, 2002).. TSC1 defined as following: Tuberous sclerosis mapped to chromosome 9q34 (TSC1 gene).. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer.. insertions defined as following: The act of putting one thing into another.. chromosome 9 defined as following: A specific pair of GROUP C CHROMSOMES of the human chromosome classification.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. variants defined as following: An alteration or difference from a norm or standard.. hamartin defined as following: An intracellular signaling and tumor suppressor protein that forms a complex with TUBEROUS SCLEROSIS COMPLEX 2 PROTEIN (TSC2) and other signaling factors to negatively regulate MTORC1 signaling and affect cell growth and proliferation. Structurally, it interacts with TSC2 through its N-terminal, which also contains GSK-3BETA phosphorylation sites and a RHO-KINASE activation domain. It also contains a C-terminal coiled-coil domain and ezrin-radixin-moesin (ERM) domain. Mutations in the TSC1 gene are associated with TUBEROUS SCLEROSIS.. genetic alterations defined as following: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.. tumor suppressor gene defined as following: Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.. TSC2 defined as following: Tuberous sclerosis mapped to chromosome 16p13.3 (TSC2 gene).. autosomal dominant disorder defined as following: An inherited disorder that manifests when one copy of a mutated gene is present.. hereditary disease defined as following: Genetic diseases are diseases in which inherited genes predispose to increased risk. The genetic disorders associated with cancer often result from an alteration or mutation in a single gene. The diseases range from rare dominant cancer family syndrome to familial tendencies in which low-penetrance genes may interact with other genes or environmental factors to induce cancer. Research may involve clinical, epidemiologic, and laboratory studies of persons, families, and populations at high risk of these disorders.. Tuberous Sclerosis defined as following: Tuberous sclerosis mapped to chromosome 9q34 (TSC1 gene)..", "label": "yes"} {"id": "converted_941", "sentence1": "Do selenoproteins and selenium play a role in prostate cancer prevention?", "sentence2": "The selenoprotein-deficient mice exhibited accelerated development of lesions associated with prostate cancer progression, implicating selenoproteins in cancer risk and development and raising the possibility that selenium prevents cancer by modulating the levels of these selenoproteins, Notably and in contrast to previous studies, RWPE-1 cells were significantly more sensitive to selenite than either of the prostate cancer cell lines. These results demonstrate that selenoproteins and selenium metabolism are regulated at multiple levels in prostate cells, In a low-selenium population, SOD2-Ala16+ men homozygous for SEPP1-Ala234 are at an increased risk of prostate cancer/aggressive prostate cancer especially if ever-smokers, because they are likely to produce more mitochondrial H(2)O(2) that they cannot remove, thereby promoting prostate tumor cell proliferation and migration., Our results support a role of selenium and polymorphisms in selenoenzymes in prostate cancer etiology, which warrants confirmation in future studies., This study provides evidence that SEP15 genetic variation may influence PCa mortality. Additionally, the association of selenium with PCa mortality was modified by a variant, suggesting the possibility that some men with PCa may benefit more from selenium than others, depending on their genotype., We conclude that decreased SEPP concentration in serum might represent an additional valuable marker for prostate cancer diagnostics., The recently completed Selenium and Vitamin E Cancer Prevention Trial (SELECT) was one of the largest human cancer prevention trials ever undertaken. Its purpose was to assess the role of selenium and vitamin E in prostate cancer prevention, but SELECT found no decline in prostate cancer., We studied Se levels in whole blood, plasma and prostate of 32 PC and 40 benign prostate hyperplasia (BPH) patients and in the control group composed of 39 healthy subjects. The selenoenzyme glutathione peroxidase (GSH-Px) was also measured in the patients' red cells, plasma and prostate tissue. Se concentration in whole blood and plasma in both groups of patients was lower as compared with controls, while in prostate gland it was significantly higher in PC than in BPH patients and controls. Red cell GSH-Px activity was the same in PC patients and controls but significantly lower in BPH patients., Of particular interest was the positive correlation between tissue GPx activity and Gleason score, with this relationship achieving statistical significance among African-Americans (r = 0.67, P = 0.02)[SEP]Relations: SELENOP has relations: disease_protein with prostate cancer, disease_protein with prostate cancer, disease_protein with prostate carcinoma, disease_protein with prostate carcinoma, disease_protein with familial prostate carcinoma, disease_protein with familial prostate carcinoma. Selenium has relations: drug_drug with Testosterone, drug_drug with Testosterone, drug_drug with Antipyrine, drug_drug with Antipyrine. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. prostate cancer defined as following: A primary or metastatic malignant tumor involving the prostate gland. The vast majority are carcinomas.. variant defined as following: An alteration or difference from a norm or standard.. SEP15 defined as following: This gene plays a role in selenium binding.. prostate hyperplasia defined as following: A disease caused by hyperplastic process of non-transformed prostatic cells.. PCa defined as following: Relief of PAIN, without loss of CONSCIOUSNESS, through ANALGESIC AGENTS administered by the patients. It has been used successfully to control POSTOPERATIVE PAIN, during OBSTETRIC LABOR, after BURNS, and in TERMINAL CARE. The choice of agent, dose, and lockout interval greatly influence effectiveness. The potential for overdose can be minimized by combining small bolus doses with a mandatory interval between successive doses (lockout interval).. SEPP defined as following: Human SELENOP wild-type allele is located in the vicinity of 5q12 and is approximately 88 kb in length. This allele, which encodes selenoprotein P, plays a role in selenium distribution.. genotype defined as following: The determination of the DNA sequence of an individual.. lesions defined as following: A localized pathological or traumatic structural change, damage, deformity, or discontinuity of tissue, organ, or body part.. red cells defined as following: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.. PC defined as following: A group of inherited ectodermal dysplasias whose most prominent clinical feature is hypertrophic nail dystrophy resulting in PACHYONYCHIA. Several specific subtypes of pachyonychia congenita have been associated with mutations in genes that encode KERATINS.. prostate tumor defined as following: Tumors or cancer of the PROSTATE.. mitochondrial defined as following: The distribution of mitochondria, including the mitochondrial genome, into daughter cells after mitosis or meiosis, mediated by interactions between mitochondria and the cytoskeleton. [GOC:mcc, PMID:10873824, PMID:11389764]. polymorphisms defined as following: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.. human defined as following: Members of the species Homo sapiens.. selenoproteins defined as following: Selenoproteins are proteins that specifically incorporate SELENOCYSTEINE into their amino acid chain. Most selenoproteins are enzymes with the selenocysteine residues being responsible for their catalytic functions..", "label": "no"} {"id": "converted_2570", "sentence1": "Is pregabalin effective for sciatica?", "sentence2": "CONCLUSIONS: Treatment with pregabalin did not significantly reduce the intensity of leg pain associated with sciatica and did not significantly improve other outcomes, as compared with placebo, over the course of 8 weeks. The incidence of adverse events was significantly higher in the pregabalin group than in the placebo group. , Whilst pregabalin (PGB) and gabapentin (GBP) are both used to treat neuropathic pain, their relative role in sciatica is unclear., GBP and PGB appeared to demonstrate comparable efficacy and SE. However, the amount and quality of evidence was low, and only indirect comparisons were available. [SEP]Relations: Pregabalin has relations: drug_effect with Pancreatitis, drug_effect with Pancreatitis, drug_effect with Menorrhagia, drug_effect with Menorrhagia, drug_drug with Pridinol, drug_drug with Pridinol, drug_effect with Pneumonia, drug_effect with Pneumonia, drug_effect with Pain, drug_effect with Pain. Definitions: PGB defined as following: Physiologically active prostaglandins found in many tissues and organs. They are potent pressor substances and have many other physiological activities.. neuropathic pain defined as following: Chronic pain caused by damage to nerve fibers. It is usually associated with tissue injury.. pregabalin defined as following: A 3-isobutyl derivative of gamma-amino butyric acid (GABA) with anti-convulsant, anti-epileptic, anxiolytic, and analgesic activities. Although the exact mechanism of action is unknown, pregabalin selectively binds to alpha2delta (A2D) subunits of presynaptic voltage-dependent calcium channels (VDCCs) located in the central nervous system (CNS). Binding of pregabalin to VDCC A2D subunits prevents calcium influx and the subsequent calcium-dependent release of various neurotransmitters, including glutamate, norepinephrine, serotonin, dopamine, and substance P, from the presynaptic nerve terminals of hyperexcited neurons; synaptic transmission is inhibited and neuronal excitability is diminished. Pregabalin does not bind directly to GABA-A or GABA-B receptors and does not alter GABA uptake or degradation.. sciatica defined as following: A condition characterized by pain radiating from the back into the buttock and posterior/lateral aspects of the leg. Sciatica may be a manifestation of SCIATIC NEUROPATHY; RADICULOPATHY (involving the SPINAL NERVE ROOTS; L4, L5, S1, or S2, often associated with INTERVERTEBRAL DISK DISPLACEMENT); or lesions of the CAUDA EQUINA.. gabapentin defined as following: A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of PARTIAL SEIZURES; NEURALGIA; and RESTLESS LEGS SYNDROME..", "label": "no"} {"id": "converted_634", "sentence1": "Could Arimidex (anastrozole) cause hot flashes?", "sentence2": "More than a third of breast cancer patients undergoing aromatase inhibitor (AI) treatment report joint pain., In the first 6 weeks, emergence of joint pain was associated with increase in general pain, fatigue, disturbed sleep, hot flashes, vaginal dryness, and decreased sexual activity., Antiestrogen therapy can cause vasomotor symptoms similar to those occurring during menopause, including hot flashes., The purpose of this study was to assess the feasibility and safety of acupuncture for treatment of hot flashes in Korean patients with breast cancer receiving antiestrogen therapy., 10 patients with breast cancer who were undergoing antiestrogen therapy with tamoxifen or anastrozole and who were suffering from hot flashes., During treatment, severity of hot flashes was reduced by 70%-95% in all patients., anastrozole has been widely used in Japan as an adjuvant treatment for postmenopausal, hormone-responsive breast cancer patients., The aim of this study is to evaluate the rate of bone fracture and bone mineral density (BMD) during anastrozole treatment in Japanese patients., Musculoskeletal disorders were the most common (26.1 %), and hot flashes were the second most common adverse event (7.9 %)., To compare the effect of therapy with anastrozole versus a combination of fulvestrant and anastrozole in women in first relapse of endocrine-responsive breast cancer., fulvestrant loading dose (LD) regimen followed by monthly injection plus 1 mg of anastrozole daily or to 1 mg of anastrozole daily alone., Incidences of prespecified adverse events (AEs) were similar. Hot flashes were more common in the experimental arm: 63 patients (24.6%) versus 35 patients (13.8%) in the standard arm (P = .0023)., The third-generation agents (anastrozole, letrozole, and exemestane) have been shown to be more effective and safer than the selective estrogen receptor modulators tamoxifen and raloxifen., AIs are well tolerated and cause a lower incidence of gynecological symptoms (vaginal bleeding, discharge, and endometrial neoplasia), venous thromboembolic events, and hot flashes compared with tamoxifen., Mood disturbances, somnolence, anxiety, fatigue, hot flashes, and memory impairment have been reported among patients receiving anastrozole as adjuvant therapy., Twenty-five PM-BC patients received, in sequence, leuprorelin, taxane-anthracycline induction chemotherapy, radiation therapy, a platinum-based intensification high-dose CT, followed by leuprorelin and anastrazole for five years., Grade 4 hematologic toxicity was observed in all patients, no patient showed a decrease of cardiac ejection fraction and hot flashes and arthralgias were of moderate intensity., Of the patients treated with anastrozole, 3 (37.5%) reported toxicity, with 1 report each of decreased libido, leg swelling, and depression (12.5%). Toxicity was reported in 2 patients taking letrozole (40%), with both reporting peripheral edema, and 1 reporting hot flashes., Patients were treated with goserelin 3.6 mg subcutaneous monthly and began anastrozole 1-mg daily 21 days after the first injection of goserelin., The most common adverse events were fatigue (50%), arthralgias (53%), and hot flashes (59%)., These studies were designed to evaluate the safety and efficacy of AIs in the following clinical settings: 1) as initial adjuvant therapy (the Arimidex, Tamoxifen, Alone or in Combination trial, Breast International Group Trial 1-98),, AIs were tolerated well, and patients who received them experienced fewer thrombolic events and less endometrial cancer, hot flashes, night sweats, and vaginal bleeding compared with patients who receive tamoxifen., It has been suggested that the association of AI and GnRh analogues and AI could block the two routes of oestrogen production in males, and therefore this approach could increase efficacy. However, it could also enhance the rate of adverse events (hot flashes, sexual impotence, etc.)., We reviewed therapeutic effects and harmful side effects in 33 patients with advanced or recurrent breast cancer who underwent treatment with Anastrozole 1 mg/day in our department., The most frequent harmful side effects were rise in total cholesterol, general fatigue, hot flashes and arthralgia (9.1%)., We analyzed the changes in frequency and severity of menopausal symptoms in patients receiving tamoxifen or aromatase inhibitors and identified factors influencing these symptoms., Both first-line tamoxifen and aromatase inhibitors induced an increase in the occurrence and severity of hot flashes (p<0.0001 and p=0.014, respectively)., To evaluate the efficacy and toxicity of the selective aromatase inhibitor anastrozole (Arimidex), we conducted a phase II trial in 53 women with asymptomatic recurrent/persistent müllerian cancer., Toxicity was modest (grade I) and infrequent, with the most common toxicities being fatigue and hot flashes., The first analysis of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial (median follow-up, 33 months) demonstrated that in adjuvant endocrine therapy for postmenopausal patients with early-stage breast cancer, anastrozole was superior to tamoxifen in terms of disease-free survival (DFS), time to recurrence (TTR), and incidence of contralateral breast cancer (CLBC)., in that endometrial cancer (P = 0.007), vaginal bleeding and discharge (P < 0.001 for both), cerebrovascular events (P < 0.001), venous thromboembolic events (P < 0.001), and hot flashes (P < 0.001) all occurred less frequently in the anastrozole group, whereas musculoskeletal disorders and fractures (P < 0.001 for both) continued to occur less frequently in the tamoxifen group., reduced nausea, hot flashes, and abdominal discomfort caused almost twice as many patients to prefer to continue with letrozole therapy than with anastrozole[SEP]Relations: Anastrozole has relations: drug_effect with Anaphylactic shock, drug_effect with Anaphylactic shock, drug_effect with Fever, drug_effect with Fever, drug_effect with Arthritis, drug_effect with Arthritis, drug_drug with Deferasirox, drug_drug with Deferasirox, drug_drug with Piroxicam, drug_drug with Piroxicam. Definitions: peripheral edema defined as following: Swelling due to an excessive accumulation of fluid in the upper or lower extremities.. hematologic defined as following: Pertaining to or related to the blood and blood-forming organs.. TTR defined as following: Transthyretin (147 aa, ~16 kDa) is encoded by the human TTR gene. This protein is involved in both the binding and transport of retinol and thyroxine.. anastrozole defined as following: A nitrile and triazole derivative that acts as a selective nonsteroidal aromatase inhibitor. It is used in the treatment of ESTROGEN NUCLEAR RECEPTOR-positive breast cancer in postmenopausal women.. estrogen receptor defined as following: Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important.. arthralgias defined as following: Pain in the joint.. endometrial neoplasia defined as following: Tumors or cancer of ENDOMETRIUM, the mucous lining of the UTERUS. These neoplasms can be benign or malignant. Their classification and grading are based on the various cell types and the percent of undifferentiated cells.. AI defined as following: Pathological condition characterized by the backflow of blood from the ASCENDING AORTA back into the LEFT VENTRICLE, leading to regurgitation. It is caused by diseases of the AORTIC VALVE or its surrounding tissue (aortic root).. toxicities defined as following: The finding of bodily harm due to the poisonous effects of something.. Tamoxifen defined as following: One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.. fulvestrant defined as following: An estradiol derivative and estrogen receptor antagonist that is used for the treatment of estrogen receptor-positive, locally advanced or metastatic breast cancer.. ATAC defined as following: Human XCL1 wild-type allele is located in the vicinity of 1q23 and is approximately 5 kb in length. This allele, which encodes lymphotactin protein, is involved in lymphocyte trafficking and inflammatory processes.. leuprorelin defined as following: A potent synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE that regulates the synthesis and release of pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE.. antiestrogen therapy defined as following: Drug treatment to block the action of the female hormone estrogen.. goserelin defined as following: A synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE. Goserelin is used in treatments of malignant NEOPLASMS of the prostate, uterine fibromas, and metastatic breast cancer.. sexual impotence defined as following: The inability in the male to have a PENILE ERECTION due to psychological or organ dysfunction.. vaginal bleeding defined as following: Vaginal bleeding unrelated to normal menstruation.. AIs defined as following: A disorder of sexual development transmitted as an X-linked recessive trait. These patients have a karyotype of 46,XY with end-organ resistance to androgen due to mutations in the androgen receptor (RECEPTORS, ANDROGEN) gene. Severity of the defect in receptor quantity or quality correlates with their phenotypes. In these genetic males, the phenotypic spectrum ranges from those with normal female external genitalia, through those with genital ambiguity as in Reifenstein Syndrome, to that of a normal male with INFERTILITY.. anxiety defined as following: Persistent and disabling ANXIETY.. fatigue defined as following: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.. Mood disturbances defined as following: A change in disposition or state of mind.. breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. vaginal dryness defined as following: An uncomfortable feeling of itching and burning in the vaginal opening resulting from inadequate vaginal lubrication. It is commonly seen during and after menopause, childbirth, or stressful conditions. It results in painful intercourse.. exemestane defined as following: An irreversible steroidal aromatase inhibitor, with antiestrogen and antineoplastic activities. Upon oral administration, exemestane binds irreversibly to and inhibits the enzyme aromatase, thereby blocking the peripheral aromatization of androgens, including androstenedione and testosterone, to estrogens. This lowers estrogen levels in the blood circulation.. musculoskeletal disorders defined as following: Diseases of the muscles and their associated ligaments and other connective tissue and of the bones and cartilage viewed collectively.. endometrial cancer defined as following: Primary or metastatic malignant neoplasm involving the endometrium (mucous membrane that lines the endometrial cavity).. somnolence defined as following: Compelling urge to sleep.. aromatase inhibitors defined as following: Compounds that inhibit AROMATASE in order to reduce production of estrogenic steroid hormones.. letrozole defined as following: A triazole and benzonitrile derivative that is a selective non-steroidal aromatase inhibitor, similar to ANASTROZOLE. It is used in the treatment of metastatic or locally advanced breast cancer in postmenopausal women.. memory impairment defined as following: Deterioration in memory function.. fractures defined as following: A traumatic injury to the bone in which the continuity of the bone is broken.. GnRh defined as following: A synthetic luteinizing hormone releasing hormone (LHRH) identical to or similar to the endogenous hormone. Synthesized in and secreted by the hypothalamus, gonadorelin binds to transmembrane LHRH receptors on pituitary gonadotrophic cells, thereby stimulating synthesis and secretion of gonadotropins. Continuous administration of gonadorelin desensitizes the gonadotrophic cells, a negative feedback effect. This agent can be used in treatment of hypothalamic amenorrhea and evaluation of hypothalamic/pituitary function.. cerebrovascular defined as following: Relating to the brain and the blood vessels that supply it..", "label": "yes"} {"id": "converted_3336", "sentence1": "Are genomic regulatory blocks (GRBs) any different than TADs?", "sentence2": "Topologically associating domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation., Clusters of CNEs define the span of regulatory inputs for many important developmental regulators and have been described previously as genomic regulatory blocks (GRBs). Their function and distribution around important regulatory genes raises the question of how they relate to 3D conformation of these loci. Here, we show that clusters of CNEs strongly coincide with topological organisation, predicting the boundaries of hundreds of topologically associating domains (TADs) in human and Drosophila. The set of TADs that are associated with high levels of noncoding conservation exhibit distinct properties compared to TADs devoid of extreme noncoding conservation. The close correspondence between extreme noncoding conservation and TADs suggests that these TADs are ancient, revealing a regulatory architecture conserved over hundreds of millions of years.Metazoan genomes contain many clusters of conserved noncoding elements. Here, the authors provide evidence that these clusters coincide with distinct topologically associating domains in humans and Drosophila, revealing a conserved regulatory genomic architecture.[SEP]Relations: Tietz syndrome has relations: disease_phenotype_positive with Congenital sensorineural hearing impairment, disease_phenotype_positive with Congenital sensorineural hearing impairment, disease_phenotype_positive with Bilateral sensorineural hearing impairment, disease_phenotype_positive with Bilateral sensorineural hearing impairment, disease_phenotype_positive with Hearing impairment, disease_phenotype_positive with Hearing impairment, disease_phenotype_positive with White eyelashes, disease_phenotype_positive with White eyelashes, disease_phenotype_positive with Autosomal dominant inheritance, disease_phenotype_positive with Autosomal dominant inheritance. Definitions: regulatory genes defined as following: Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.. TADs defined as following: Tietz syndrome is a genetic hypopigmentation and deafness syndrome characterized by congenital profound bilateral sensorineural hearing loss and generalized albino-like hypopigmentation of skin, eyes and hair.. humans defined as following: Members of the species Homo sapiens..", "label": "no"} {"id": "converted_3090", "sentence1": "Is eculizumab used for treatment of myasthenia gravis?", "sentence2": "Eculizumab treatment improved symptoms compared with placebo in a phase II study in patients with refractory gMG. D, Eculizumab (Soliris) has been approved in several countries for refractory forms of generalized seropositive severe myasthenia gravis. , The humanized monoclonal antibody eculizumab (Soliris®) is a complement inhibitor indicated for use in anti-acetylcholine receptor (AChR) antibody-positive adults with generalized myasthenia gravis (gMG) in the USA, refractory gMG in the EU, or gMG with symptoms that are difficult to control with high-dose IVIg therapy or PLEX in Japan. , Although several questions remain, such as duration of treatment, cost effectiveness and long-term efficacy and tolerability, current evidence indicates that eculizumab is a valuable emerging therapy for patients with refractory gMG., The 2 exceptions are acetylcholinesterase inhibitors and complement inhibition with eculizumab, which was recently approved by the US Food and Drug Administration for myasthenia gravis., INTRODUCTION\nA phase 2 study of eculizumab for treating myasthenia gravis (MG) used the quantitative myasthenia gravis score (QMG) and myasthenia gravis activities of daily living profile (MG-ADL) to evaluate baseline disease severity and treatment response., QMG and MG-ADL correlations: Study of eculizumab treatment of myasthenia gravis., Rituximab seems to be particularly effective in MuSK myasthenia gravis, and eculizumab arises as an option in refractory AChR myasthenia gravis., Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis., Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study., The humanized monoclonal antibody eculizumab (Soliris®) is a complement inhibitor indicated for use in anti-acetylcholine receptor (AChR) antibody-positive adults with generalized myasthenia gravis (gMG) in the USA, refractory gMG in the EU, or gMG with symptoms that are difficult to control with high-dose IVIg therapy or PLEX in Japan., Eculizumab (Soliris) has been approved in several countries for refractory forms of generalized seropositive severe myasthenia gravis., Eculizumab: A Review in Generalized Myasthenia Gravis., A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis., Eculizumab: A Review in Generalized Myasthenia Gravis.) , INTRODUCTION: A phase 2 study of eculizumab for treating myasthenia gravis (MG) used the quantitative myasthenia gravis score (QMG) and myasthenia gravis activities of daily living profile (MG-ADL) to evaluate baseline disease severity and treatment response., Correlations were then analyzed between these assessments.Respond with exceptions, completions and modifications or revisions done before completion
. Stress incontinence defined as following: Involuntary discharge of URINE as a result of physical activities that increase abdominal pressure on the URINARY BLADDER without detrusor contraction or overdistended bladder. The subtypes are classified by the degree of leakage, descent and opening of the bladder neck and URETHRA without bladder contraction, and sphincter deficiency.. incontinence defined as following: Involuntary passage of stool or urine from the body.. pelvic floor defined as following: Soft tissue formed mainly by the pelvic diaphragm, which is composed of the two levator ani and two coccygeus muscles. The pelvic diaphragm lies just below the pelvic aperture (outlet) and separates the pelvic cavity from the PERINEUM. It extends between the PUBIC BONE anteriorly and the COCCYX posteriorly..", "label": "yes"} {"id": "converted_4244", "sentence1": "Is Adamts18 deficiency associated with cancer?", "sentence2": "Adamts18 deficiency promotes colon carcinogenesis by enhancing β-catenin and p38MAPK/ERK1/2 signaling in the mouse model of AOM/DSS-induced colitis-associated colorectal cancer., ADAMTS18 is a novel tumor suppressor and is critical to the pathology of human colorectal cancer. However, the underlying mechanism is not clear. Here we generated an Adamts18-deficient mouse strain as an in vivo model to investigate the role of ADAMTS18 in the pathogenesis of colorectal cancer. In AOM/DSS-induced colitis-associated colorectal cancer, the deficiency of Adamts18 in mice resulted in enhanced tumorigenesis and colon inflammation that could be attributed in part to enhanced nuclear translocation of β-catenin and elevated expression of its downstream target genes, cyclin D1 and c-myc. Moreover, increased p38MAPK and ERK1/2 activities were detected in colon cancer cells from Adamts18-deficient mice. Further studies revealed that ADAMTS18 deficiency reduced intestinal E-cadherin levels in mice, which ultimately led to intestinal barrier dysfunction. These data indicate that Adamts18 deficiency enhances tumorigenesis and intestinal inflammation through elevated Wnt/β-catenin and p38MAPK/ERK1/2 signaling and promotes colon cancer in this mouse model.[SEP]Relations: ADAMTS18 has relations: disease_protein with colorectal cancer, disease_protein with colorectal cancer, disease_protein with colorectal carcinoma, disease_protein with colorectal carcinoma, disease_protein with colorectal neoplasm, disease_protein with colorectal neoplasm, protein_protein with B3GLCT, protein_protein with B3GLCT, protein_protein with IGKC, protein_protein with IGKC. Definitions: colon cancer defined as following: A primary or metastatic malignant neoplasm that affects the colon. Representative examples include carcinoma, lymphoma, and sarcoma.. human defined as following: Members of the species Homo sapiens.. cyclin D1 defined as following: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.. intestinal inflammation defined as following: A reaction characterizeds by capillary dilatation, leukocytic infiltration, redness, heat, pain, swelling localized to the in the intestinal tract. [PMID:9897960]. intestinal defined as following: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.. colon inflammation defined as following: Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER.. cancer defined as following: A malignant tumor at the original site of growth..", "label": "yes"} {"id": "converted_3364", "sentence1": "Is PRDM9 essential for meiosis?", "sentence2": "Our findings do not identify the nature of the underlying DNA sequences, but argue against the proposed role of Prdm9 as an essential transcription factor in mouse meiosis, PRDM9 gene polymorphism may not be associated with defective spermatogenesis in the Chinese Han population, PRDM9 is essential for the progression through early meiotic prophase, including double strand break repair, homologous chromosome pairing, and sex body formation during spermatogenesis. , PRDM9 (PR domain-containing protein 9) is a meiosis-specific protein that trimethylates H3K4 and controls the activation of recombination hot spots. It is an essential enzyme in the progression of early meiotic prophase., In many eukaryotes, sites of meiotic recombination, also called hotspots, are regions of accessible chromatin, but in many vertebrates, their location follows a distinct pattern and is specified by PR domain-containing protein 9 (PRDM9). , We found that although the post-SET zinc finger and the KRAB domains are not essential for the methyltransferase activity of PRDM9 in cell culture, the KRAB domain mutant mice show only residual PRDM9 methyltransferase activity and undergo meiotic arrest. In aggregate, our data indicate that domains typically involved in regulation of gene expression do not serve that role in PRDM9, but are likely involved in setting the proper chromatin environment for initiation and completion of homologous recombination., PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites.[SEP]Relations: transcription factor binding has relations: molfunc_protein with PRKDC, molfunc_protein with PRKDC, molfunc_protein with KDM1A, molfunc_protein with KDM1A, molfunc_protein with KDM1B, molfunc_protein with KDM1B, molfunc_protein with PSMD10, molfunc_protein with PSMD10. siRNA binding has relations: molfunc_protein with TLR9, molfunc_protein with TLR9. Definitions: Binding Sites defined as following: The parts of a macromolecule that directly participate in its specific combination with another molecule.. sites defined as following: A position in relation to its surroundings.. DNA sequences defined as following: The sequence of nucleotide residues along a DNA chain.. transcription factor defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. eukaryotes defined as following: Organism or cells with a nucleus separated from the cytoplasm by a two membrance nuclear envelope and compartmentalization of function into distinct cytoplasmic organelles.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. vertebrates defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes..", "label": "yes"} {"id": "converted_3080", "sentence1": "Is treatment with Bacillus Calmette Guerin used for bladder cancer?", "sentence2": "Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer. , this result indicates that they may be used as putative biomarkers for monitoring changes in bladder carcinogenesis in response to BCG immunotherapy., response of urothelial precancerous lesions to intravesical BCG treatment, bladder cancer (BC) is a major clinical issue.METHODS: We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT + intravesical instillations of bacillus Calmette-Guerin (BCG)., To evaluate the efficacy and safety of a tailored endovesical immunotherapy protocol with biweekly BCG for elderly Patients with high risk non muscle invasive bladder cancer , Bacillus of Calmette-Guerin (BCG) therapy for high risk non muscle invasive bladder cancer treatment in older patients., BCG (Bacillus of Calmette Guerin) has been used for more than 20 years and is currently the most active agent for superficial bladder cancer therapy., BCG (Bacillus of Calmette Guerin) therapy of high-risk superficial bladder cancer., Production of IL-5, a classical T(H)2 cytokine, following bacillus Calmette guerin immunotherapy of bladder cancer., Intravesical Bacillus Calmette-Guerin is used to treat patients with superficial bladder cancer., There is some evidence that BCG therapy improves survival and progression rates of patients with high-risk superficial bladder cancer decreasing the proportion who require radical cystectomy., Local immunotherapy with bacillus Calmette-Guerin (BCG) is an effective and frequently used treatment for superficial bladder cancer., CONCLUSIONS\nIntravesical bacillus Calmette-Guerin is a viable therapeutic option in patients with high risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low dose oral steroids or treatment with inhaled steroids., PURPOSE\nBacillus Calmette-Guerin is the most effective therapy for nonmuscle invasive bladder cancer., INTRODUCTION\nBacillus Calmette-Guerin (BCG) is a live attenuated strain of Mycobacterium bovis that has been used to treat urothelial carcinoma since 1976, and has been reported to eradicate disease in more than 70% of patients with in situ and stage I disease., Intravesical administration of bacillus Calmette-Guerin has been shown to be highly effective treatment of superficial bladder cancer., Intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: effect of bacillus Calmette-Guerin viability on treatment results., We describe a 53 year- old man with a disseminated bacillus Calmette-Guerin (BCG) infection after intravescical instillation for bladder carcinoma., We tested the hypothesis that tumor expression of natural cytotoxicity receptor ligands can serve as a predictive factor for the response to intravesical bacillus Calmette-Guerin in patients with nonmuscle invasive, high grade bladder cancer., Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer., Pancreatic and psoas abscesses as a late complication of intravesical administration of bacillus Calmette-Guerin for bladder cancer: a case report and review of the literature.This case illustrates the fact that although intravesical administration of bacillus Calmette-Guerin is generally considered to be safe, it is not exempt from complications and these could appear immediately after treatment or as a delayed complication many years later., Effects of local bacillus Calmette-Guerin therapy in patients with bladder carcinoma on immunocompetent cells of the bladder wall.The antitumoral effects of intravesical bacillus Calmette-Guerin against recurrent superficial urothelial bladder cancer seem to be linked to immunological effector mechanisms. , Fatal sepsis following intravesical bacillus Calmette-Guerin administration for bladder cancer.Intravesical administration of bacillus Calmette-Guerin has been shown to be highly effective treatment of superficial bladder cancer. , Intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: effect of bacillus Calmette-Guerin viability on treatment results.We treated 40 patients with superficial bladder cancer via intravesical bacillus Calmette-Guerin for 1) prophylaxis against tumor recurrence, 2) residual carcinoma or 3) flat carcinoma in situ. , Bacillus Calmette-Guerin immunotherapy for bladder cancer.Bacillus Calmette-Guerin immunotherapy has been found by a number of investigators to be effective in the treatment and prevention of superficial bladder cancer. , Safety and efficacy of intravesical bacillus Calmette-Guerin instillations in steroid treated and immunocompromised patients.Intravesical bacillus Calmette-Guerin is a viable therapeutic option in patients with high risk superficial bladder cancer and concomitant lymphoma or chronic lymphocytic leukemia, treatment with low dose oral steroids or treatment with inhaled steroids. , Our results suggest that intralesional bacillus Calmette-Guerin immunotherapy can afford long term protection from transplanted bladder cancer, and that live bacillus Calmette-Guerin is superior to levamisole and P3 + Re-glycolipid + bacillus Calmette-Guerin cell walls in the treatment of bladder cancer., A randomized controlled prospective evaluation of intravesical and percutaneous bacillus Calmette-Guerin immunotherapy was done in 57 patients with transitional cell carcinoma of the bladder., Up to 90% of patients with high grade superficial bladder tumors experience tumor recurrence and up to 50% have progression despite bacillus Calmette-Guerin treatment., We review how the bacillus Calmette-Guerin vaccine evolved to become standard therapy for superficial bladder cancer., We reviewed the historical literature describing the origin of the bacillus Calmette-Guerin vaccine as an anticancer agent and its singular success as the most effective immunotherapy used against a human neoplasm.[SEP]Relations: Bacillus calmette-guerin substrain tice live antigen has relations: drug_drug with Antithymocyte immunoglobulin (rabbit), drug_drug with Antithymocyte immunoglobulin (rabbit), drug_drug with Siltuximab, drug_drug with Siltuximab, drug_drug with Paclitaxel, drug_drug with Paclitaxel, drug_drug with Hydroxychloroquine, drug_drug with Hydroxychloroquine, drug_drug with Inosine pranobex, drug_drug with Inosine pranobex. Definitions: MSH2 defined as following: DNA mismatch repair protein Msh2 (934 aa, ~105 kDa) is encoded by the human MSH2 gene. This protein is involved in DNA mismatch repair.. levamisole defined as following: An antihelminthic drug that has been tried experimentally in rheumatic disorders where it apparently restores the immune response by increasing macrophage chemotaxis and T-lymphocyte function. Paradoxically, this immune enhancement appears to be beneficial in rheumatoid arthritis where dermatitis, leukopenia, and thrombocytopenia, and nausea and vomiting have been reported as side effects. (From Smith and Reynard, Textbook of Pharmacology, 1991, p435-6). steroid defined as following: A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed). Bacillus Calmette-Guerin defined as following: An attenuated form of Mycobacterium bovis that is used to generate the Bacillus Calmette-Guerin vaccine.. lymphoma defined as following: A general term for various neoplastic diseases of the lymphoid tissue.. MSI defined as following: The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.. urothelial carcinoma defined as following: A malignant neoplasm derived from the transitional epithelium of the urinary tract (urinary bladder, ureter, urethra, or renal pelvis). It is frequently papillary.. HER-2 defined as following: A cancer vaccine comprised of peptides derived from the extracellular domain of the tumor-associated antigen Her-2/neu with potential antineoplastic activity. HER-2/neu peptide vaccine may induce antibodies with anti-tumor activity and may also elicit a specific CD8 T-cell response against specific tumor cell types. (NCI04). IL-5 defined as following: Binding to interleukin-5. [GOC:jl]. T1 defined as following: This gene plays a role in energy metabolism and mitochondrial ADP/ATP flux.. psoas abscesses defined as following: Abscess of the PSOAS MUSCLES resulting usually from disease of the lumbar vertebrae, with the pus descending into the muscle sheath. The infection is most commonly tuberculous or staphylococcal.. predictive factor defined as following: Characteristics and conditions that have a bearing on the likelihood of a person developing a disease or disorder.. Pancreatic defined as following: Peptide hormones secreted into the blood by cells in the ISLETS OF LANGERHANS of the pancreas. The alpha cells secrete glucagon; the beta cells secrete insulin; the delta cells secrete somatostatin; and the PP cells secrete pancreatic polypeptide.. MLH1 defined as following: This gene plays a role in DNA mismatch repair.. TURBT defined as following: A surgical procedure used to treat bladder tumors, during which a resectoscope is passed through the urethra and into the bladder.. bladder defined as following: A musculomembranous sac along the URINARY TRACT. URINE flows from the KIDNEYS into the bladder via the ureters (URETER), and is held there until URINATION.. transitional cell carcinoma defined as following: A malignant neoplasm derived from TRANSITIONAL EPITHELIAL CELLS, occurring chiefly in the URINARY BLADDER; URETERS; or RENAL PELVIS.. chronic lymphocytic leukemia defined as following: A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.. superficial bladder cancer defined as following: An infiltrating carcinoma of the bladder that has not invaded into the bladder muscularis propria.. bladder tumor defined as following: Tumors or cancer of the URINARY BLADDER.. Mycobacterium bovis defined as following: The bovine variety of the tubercle bacillus. It is called also Mycobacterium tuberculosis var. bovis.. bladder carcinoma defined as following: A carcinoma arising from the bladder epithelium. Approximately 90% of the bladder carcinomas are transitional cell carcinomas. The remainder are squamous cell carcinomas, adenocarcinomas and small cell neuroendocrine carcinomas.. human defined as following: Members of the species Homo sapiens.. bladder cancer defined as following: A primary or metastatic malignant neoplasm involving the bladder.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary..", "label": "yes"} {"id": "converted_4359", "sentence1": "Is proton beam therapy used for treatment of craniopharyngioma?", "sentence2": " The majority of children had adjuvant therapy comprising proton beam therapy (18/59; 30.5%) or conventional radiotherapy (16/59; 27.1%)., Proton Therapy for Craniopharyngioma - An Early Report from a Single European Centre., AIMS: Proton beam therapy (PBT) is being increasingly used for craniopharyngioma. , MATERIALS AND METHODS: Between August 2013 and July 2016, 18 patients with craniopharyngiomas were treated with 54 Cobalt Gray Equivalent (CGE) in 30 fractions over 6 weeks at our centre., CONCLUSIONS: Our early results are encouraging and comparable with the limited literature on PBT for craniopharyngioma., All of the other patients underwent proton-beam radiotherapy with no documented tumor growth (median follow-up: 20 months; range 5.1-29.9 months)., Where aggressive subtotal resection is achieved, patients should be closely followed, with radiation initiated at the time of progression or recurrence-ideally via proton beam therapy, although three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and stereotactic radiosurgery are very appropriate in a range of circumstances, governed by access, patient age, disease architecture, and character of the recurrence., This study examined parental distress in a sample of families of patients with Cp treated with proton beam therapy to identify factors for targeting psychological intervention.PROCEDURE: Prior to (n = 96) and 1 year after (n = 73) proton therapy, parents of children diagnosed with Cp (9.81 ± 4.42 years at baseline; 49% male) completed a self-report measure of distress, the Brief Symptom Inventory (BSI)., Diagnoses included medulloblastoma, craniopharyngioma, ependymoma, glial tumors, germ cell tumors, and others., Initial experience with proton beam therapy in childhood-onset craniopharyngioma patients shows promising results in terms of more protective radiological treatment. , Monte Carlo simulations were used to assess secondary neutron doses received by patients treated with proton therapy for ocular melanoma and craniopharyngioma., Secondary neutron doses in proton therapy treatments of ocular melanoma and craniopharyngioma., AIMS: Proton beam therapy (PBT) is being increasingly used for craniopharyngioma., LTS: Published reports suggest a benefit to proton beam therapy for use in tumors of the skull base, including craniopharyngiomas, chordomas, skull-base sarcomas, and unresectable meningiomas.CONC, In recent years, proton therapy (PT), with its physical properties of heavy ion beam, that is, Prague peak phenomenon, has been more frequently used in patients with craniopharyngioma., Proton beam therapy versus conformal photon radiation therapy for childhood craniopharyngioma: multi-institutional analysis of outcomes, cyst dynamics, and toxicity., PURPOSE: We compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxicity., Proton therapy for craniopharyngioma in adults: a protocol for systematic review and meta-analysis., We hereby report a case of a 7-year-old boy with a craniopharyngioma which had been subtotally resected and was subsequently treated with modern pencil beam proton therapy under high-precision image guidance., Pencil beam scanning proton therapy for the treatment of craniopharyngioma complicated with radiation-induced cerebral vasculopathies: A dosimetric and linear energy transfer (LET) evaluation., tial experience with proton beam therapy in childhood-onset craniopharyngioma patients shows promising results in terms of more protective radiological treatment. R, PURPOSE: We compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxic, BACKGROUND AND PURPOSE: This study analyses the dosimetric and dose averaged Linear Energy transfer (LETd) correlation in paediatric craniopharyngioma (CP) patients with and without radiation-induced cerebral vasculopathies (RICVs) treated with pencil beam scanning (PBS) pro, OBJECTIVE: The authors compared survival and multiple comorbidities in children diagnosed with craniopharyngioma who underwent gross-total resection (GTR) versus subtotal resection (STR) with radiation therapy (RT), either intensity-modulated radiation therapy (IMRT) or proton beam therapy (P, Proton Therapy for Craniopharyngioma - An Early Report from a Single European Centre, s. Some studies have shown that PT has advantages in the treatment of craniopharyngioma in adu, Postoperative cerebral glucose metabolism in pediatric patients receiving proton therapy for craniopharyngioma, Clinical equipoise: Protons and the child with craniopharyngioma., skull base. More public attention has been given to proton beam therapy due to the increasing number of centers now in operation or in the planning stages for offering this treatment option.METHODS: We reviewed the physical properties of protons and the clinical studies performed to justify their use in the management of skull-base tumors and determine the benefits of proton beam therapy.RESULTS: Published reports suggest a benefit to proton beam therapy for use in tumors of the skull base, including craniopharyngiomas, chordomas, skull-base sarcomas, and unresectable meningiomas.CONCLUSIONS: Use of proton beam th, PURPOSE: We report the results of the early cohort of patients treated for craniopharyngioma with combined proton-photon irradiation at the Massachusetts General Hospital and the Harvard Cyclotron Laboratory.METHODS AND MATERIALS: Between 1981 and 1988, 15 patients with craniopharyngioma were treated in part or entirely with fractiona, UNLABELLED: This retrospective preliminary review evaluated the efficacy and toxicity of fractionated proton radiotherapy in the management of pediatric craniopharyngioma.METHODS: Sixteen patients, aged 7-34 years, were treated with p, population. We evaluated the outcomes of all adult craniopharyngioma patients treated at our institution using proton therapy to report outcomes for disease control, treatment-related toxicity, and tumor response.METHODS: We analyzed 14 adult patie, Proton radiation has been used safely and effectively for medulloblastoma, primitive neuro-ectodermal tumors, craniopharyngioma, ependymoma, germ cell intracranial tumors, low-grade glioma, retinoblastoma, rhabdomyosarcoma and other soft tissue sarcomas, Ewing's sarcoma and other bone sarcomas., ontroversial. The purpose of this study was to evaluate the efficacy and safety of PT for craniopharyngioma in adults.METHODS AND ANALYSIS: We will search six databases (MEDLINE, EMBASE, Web of Science, the Cochrane Library, Amed, Scopus), clinical research registration websites and grey literature, aiming to identify randomised controlled trials (RCTs) on PT for craniopharyngioma in adults between 1[SEP]Relations: craniopharyngioma has relations: disease_protein with CTNNB1, disease_protein with CTNNB1, disease_phenotype_positive with Headache, disease_phenotype_positive with Headache, disease_disease with disease of facial skeleton, disease_disease with disease of facial skeleton, disease_phenotype_positive with Bitemporal hemianopia, disease_phenotype_positive with Bitemporal hemianopia, disease_disease with bone benign neoplasm, disease_disease with bone benign neoplasm. Definitions: protons defined as following: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion.. soft tissue sarcomas defined as following: A malignant neoplasm arising from muscle tissue, adipose tissue, blood vessels, fibrous tissue, or other supportive tissues excluding the bones.. medulloblastoma defined as following: A malignant neoplasm that may be classified either as a glioma or as a primitive neuroectodermal tumor of childhood (see NEUROECTODERMAL TUMOR, PRIMITIVE). The tumor occurs most frequently in the first decade of life with the most typical location being the cerebellar vermis. Histologic features include a high degree of cellularity, frequent mitotic figures, and a tendency for the cells to organize into sheets or form rosettes. Medulloblastoma have a high propensity to spread throughout the craniospinal intradural axis. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2060-1). LET defined as following: Rate of energy dissipation along the path of charged particles. In radiobiology and health physics, exposure is measured in kiloelectron volts per micrometer of tissue (keV/micrometer T).. ependymoma defined as following: Glioma derived from EPENDYMOGLIAL CELLS that tend to present as malignant intracranial tumors in children and as benign intraspinal neoplasms in adults. It may arise from any level of the ventricular system or central canal of the spinal cord. Intracranial ependymomas most frequently originate in the FOURTH VENTRICLE and histologically are densely cellular tumors which may contain ependymal tubules and perivascular pseudorosettes. Spinal ependymomas are usually benign papillary or myxopapillary tumors. (From DeVita et al., Principles and Practice of Oncology, 5th ed, p2018; Escourolle et al., Manual of Basic Neuropathology, 2nd ed, pp28-9). disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown.. bone sarcomas defined as following: A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed). germ cell tumors defined as following: A benign or malignant, gonadal or extragonadal neoplasm that originates from germ cells. Representative examples include teratoma, seminoma, embryonal carcinoma, and yolk sac tumor.. glial tumors defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21). retinoblastoma defined as following: A malignant tumor arising from the nuclear layer of the retina that is the most common primary tumor of the eye in children. The tumor tends to occur in early childhood or infancy and may be present at birth. The majority are sporadic, but the condition may be transmitted as an autosomal dominant trait. Histologic features include dense cellularity, small round polygonal cells, and areas of calcification and necrosis. An abnormal pupil reflex (leukokoria); NYSTAGMUS, PATHOLOGIC; STRABISMUS; and visual loss represent common clinical characteristics of this condition. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2104). craniopharyngioma defined as following: A benign pituitary-region neoplasm that originates from Rathke's pouch. The two major histologic and clinical subtypes are adamantinous (or classical) craniopharyngioma and papillary craniopharyngioma. The adamantinous form presents in children and adolescents as an expanding cystic lesion in the pituitary region. The cystic cavity is filled with a black viscous substance and histologically the tumor is composed of adamantinomatous epithelium and areas of calcification and necrosis. Papillary craniopharyngiomas occur in adults, and histologically feature a squamous epithelium with papillations. (From Joynt, Clinical Neurology, 1998, Ch14, p50). toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. PBT defined as following: Mast/stem cell growth factor receptor Kit (976 aa, ~110 kDa) is encoded by the human KIT gene. This protein is involved in cell survival, tyrosine phosphorylation and ligand-mediated signaling.. germ cell defined as following: The reproductive cells in multicellular organisms at various stages during GAMETOGENESIS.. rhabdomyosarcoma defined as following: A malignant mesenchymal tumor with skeletal muscle differentiation affecting the anus.. Ewing's sarcoma defined as following: A small round cell bone tumor that lacks morphologic, immunohistochemical, and electron microscopic evidence of neuroectodermal differentiation. It represents one of the two ends of the spectrum called Ewing sarcoma/peripheral neuroectodermal tumor. It often affects the diaphysis or metaphyseal-diaphyseal portion of long bones. Clinical findings include pain and a mass in the involved area. Fever, anemia, leukocytosis, and an increased sedimentation rate are often seen. X-ray examination reveals osteolytic lesions. The prognosis depends on the stage, anatomic location, and size of the tumor.. chordomas defined as following: A malignant tumor arising from the embryonic remains of the notochord. It is also called chordocarcinoma, chordoepithelioma, and notochordoma. (Dorland, 27th ed). tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. ocular melanoma defined as following: A melanoma that arises from the structures of the eye or ocular adnexa..", "label": "yes"} {"id": "converted_3563", "sentence1": "Are genes that escape X-chromosome inactivation related to mental impairment?", "sentence2": "Mutation screening of the MECP2 gene in a large cohort of 613 fragile-X negative patients with mental retardation., The first one, the double nucleotide substitution c.1162_1163delinsTA leading to a premature stop codon (p.Pro388X) was found in a female patient with random X-inactivation, presenting with borderline mental impairment without any features of Rett syndrome. , the c.679C>G substitution, changing a glutamine to a glutamate in the transcriptional repression functional domain (p.Gln227Glu), was found in a female patient with a moderately biased X-chromosome inactivation profile and presenting with mild intellectual delay and minor psychotic features, Genes that escape X-inactivation in humans have high intraspecific variability in expression, are associated with mental impairment but are not slow evolving., The newly described escape genes cluster on the X chromosome in the same chromosomal regions as the previously known escapees. There is an excess of escaping genes associated with mental retardation, consistent with this being a common phenotype of polyX phenotypes.[SEP]Relations: Intellectual disability has relations: disease_phenotype_positive with partial deletion of the short arm of chromosome 7, disease_phenotype_positive with partial deletion of the short arm of chromosome 7, disease_phenotype_positive with chromosome 18p deletion syndrome, disease_phenotype_positive with chromosome 18p deletion syndrome, disease_phenotype_positive with chromosome 11p13 deletion syndrome, distal, disease_phenotype_positive with chromosome 11p13 deletion syndrome, distal, disease_phenotype_positive with chromosome 10q23 deletion syndrome, disease_phenotype_positive with chromosome 10q23 deletion syndrome, disease_phenotype_positive with chromosome 18q deletion syndrome, disease_phenotype_positive with chromosome 18q deletion syndrome. Definitions: glutamine defined as following: A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.. humans defined as following: Members of the species Homo sapiens.. MECP2 gene defined as following: This gene plays a role in both the recognition of DNA methylation and the regulation of transcription.. mental impairment defined as following: A change to an individual's judgment, orientation (to place, time, and self), intellectual functioning, or mood from their baseline.. substitution defined as following:Definition: Indicates that the subject Act has undergone or should undergo substitution of a type indicated by Act.code.
Rationale: Used to specify \"allowed\" substitution when creating orders, \"actual\" susbstitution when sending events, as well as the reason for the substitution and who was responsible for it.
. mental retardation defined as following: Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28). Genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. Rett syndrome defined as following: An inherited neurological developmental disorder that is associated with X-LINKED INHERITANCE and may be lethal in utero to hemizygous males. The affected female is normal until the age of 6-25 months when progressive loss of voluntary control of hand movements and communication skills; ATAXIA; SEIZURES; autistic behavior; intermittent HYPERVENTILATION; and HYPERAMMONEMIA appear. (From Menkes, Textbook of Child Neurology, 5th ed, p199). premature stop codon defined as following: An amino acid-specifying codon that has been converted to a stop codon (CODON, TERMINATOR) by mutation. Its occurance is abnormal causing premature termination of protein translation and results in production of truncated and non-functional proteins. A nonsense mutation is one that converts an amino acid-specific codon to a stop codon.. X chromosome defined as following: The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"} {"id": "converted_604", "sentence1": "Has the fungus Ashbya gossypii got many nuclei that share cytoplasm?", "sentence2": "multinucleated Ashbya gossypii cells., multinucleated Ashbya gossypii fungal cells, Nuclei in the filamentous, multinucleated fungus Ashbya gossypii divide asynchronously. , multinucleated Ashbya gossypii cells, We analyzed a unique asynchronous nuclear division cycle in a multinucleated filamentous fungus, Ashbya gossypii., multinucleated hyphae in Ashbya gossypii., We have followed the migration of GFP-labelled nuclei in multinucleate hyphae of Ashbya gossypii, multinucleate fungus Ashbya gossypii, Ashbya gossypii grows as multinucleated and constantly elongating hyphae, multinucleated hyphae of Ashbya gossypii., We report the mechanistic basis guiding the migration pattern of multiple nuclei in hyphae of Ashbya gossypii. , multinucleate fungal cells, multinucleate Ashbya gossypii cells relies on a minimal network of genes, Clustering of nuclei in multinucleated hyphae is prevented by dynein-driven bidirectional nuclear movements and microtubule growth control in Ashbya gossypii., In the multinucleate fungus Ashbya gossypii, cytoplasmic microtubules (cMTs) emerge from the spindle pole body outer plaque (OP) in perpendicular and tangential directions., multinucleated hyphae of Ashbya gossypii., multiple nuclei in Ashbya gossypii hyphae, Ashbya gossypii has a budding yeast-like genome but grows exclusively as multinucleated hyphae.[SEP]Relations: cytoplasmic microtubule has relations: cellcomp_protein with SPACA9, cellcomp_protein with SPACA9, cellcomp_protein with TOGARAM1, cellcomp_protein with TOGARAM1, cellcomp_protein with C4orf47, cellcomp_protein with C4orf47, cellcomp_protein with ARHGAP18, cellcomp_protein with ARHGAP18, cellcomp_protein with SYBU, cellcomp_protein with SYBU. Definitions: cytoplasmic microtubules defined as following: Any microtubule in the cytoplasm of a cell. [GOC:mah]. cytoplasm defined as following: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990).", "label": "yes"} {"id": "converted_764", "sentence1": "Is insulin-like growth factor-I (IGF-I) able to affect tendon protein synthesis in classic Ehlers-Danlos syndrome patients?", "sentence2": "Tendon protein synthesis rate in classic Ehlers-Danlos patients can be stimulated with insulin-like growth factor-I, IGF-I injections significantly increased FSR values in cEDS patients but not in controls, In conclusion, baseline protein synthesis rates in connective tissue appeared normal in cEDS patients, and the patients responded with an increased tendon protein synthesis rate to IGF-I injections, In conclusion, baseline protein synthesis rates in connective tissue appeared normal in cEDS patients, and the patients responded with an increased tendon protein synthesis rate to IGF-I injections, IGF-I injections significantly increased FSR values in cEDS patients but not in controls (delta values: cEDS 0[SEP]Relations: insulin-like growth factor I binding has relations: molfunc_protein with IGF1R, molfunc_protein with IGF1R, molfunc_protein with IGFBP4, molfunc_protein with IGFBP4, molfunc_protein with IGFBP3, molfunc_protein with IGFBP3, molfunc_protein with IGFBP1, molfunc_protein with IGFBP1, molfunc_protein with IGFBP5, molfunc_protein with IGFBP5. Definitions: insulin-like growth factor-I defined as following: A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.. FSR defined as following: A descriptor of spinal somatic dysfunction used to denote a combination flexed (F), sidebent (S), and rotated (R) vertebral position.. cEDS defined as following: Autoimmune lymphoproliferative syndrome due to mutations in CASPASE 8 gene.. connective tissue defined as following: Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX.. IGF-I defined as following: Human IGF1 wild-type allele is located within 12q22-q23 and is approximately 85 kb in length. This allele, which encodes insulin-like growth factor I protein, is involved in the mediation of peptides that exert growth-promoting effects involved in mammalian growth and development.. Ehlers-Danlos syndrome defined as following: A heterogeneous group of autosomally inherited COLLAGEN DISEASES caused by defects in the synthesis or structure of FIBRILLAR COLLAGEN. There are numerous subtypes: classical, hypermobility, vascular, and others. Common clinical features include hyperextensible skin and joints, skin fragility and reduced wound healing capability..", "label": "yes"} {"id": "converted_2266", "sentence1": "Are neurexins localized at pre-synapses?", "sentence2": "Neurexins and neuroligins are two distinct families of single-pass transmembrane proteins localized at pre- and postsynapses, respectively. , presynaptic neurexins, best-characterized transsynaptic interactions are formed by presynaptic neurexins, which bind to diverse postsynaptic ligands., presynaptic neurexin[SEP]Relations: protein transport within plasma membrane has relations: bioprocess_bioprocess with protein transport within lipid bilayer, bioprocess_bioprocess with protein transport within lipid bilayer, bioprocess_bioprocess with protein transport out of plasma membrane raft, bioprocess_bioprocess with protein transport out of plasma membrane raft.", "label": "yes"} {"id": "converted_415", "sentence1": "Can protein coding exons originate from ALU sequences?", "sentence2": "The Alu element has been a major source of new exons during primate evolution. Thousands of human genes contain spliced exons derived from Alu elements., More than 25% of Alu exons analyzed by RNA-Seq have estimated transcript inclusion levels of at least 50% in the human cerebellum, indicating widespread establishment of Alu exons in human genes., his study presents genomic evidence that a major functional consequence of Alu exonization is the lineage-specific evolution of translational regulation., Our data suggests that lineage-specific exonization events should be determined by the combination event of the formation of splicing sites and protection against site-specific mutation pressures. These evolutionary mechanisms could be major sources for primate diversification., Exonization of Alu elements creates primate-specific genomic diversity, Our data show that, once acquired, some exonizations were lost again in some lineages. In general, Alu exonization occurred at various time points over the evolutionary history of primate lineages, and protein-coding potential was acquired either relatively soon after integration or millions of years thereafter., Once integrated, they have the potential to become exapted as functional modules, e.g., as protein-coding domains via alternative splicing. This particular process is also termed exonization and increases protein versatility, alternative \"Alu-exons\" also carry the potential to greatly enhance genetic diversity by increasing the transcriptome of primates chiefly via alternative splicing., ere, we report a 5' exon generated from one of the two alternative transcripts in human tumor necrosis factor receptor gene type 2 (p75TNFR) that contains an ancient Alu-SINE, which provides an alternative N-terminal protein-coding domain.[SEP]Relations: Antigen processing: Ubiquitination & Proteasome degradation has relations: pathway_protein with ELOC, pathway_protein with ELOC, pathway_protein with UNKL, pathway_protein with UNKL, pathway_protein with GLMN, pathway_protein with GLMN, pathway_protein with AREL1, pathway_protein with AREL1, pathway_protein with ASB10, pathway_protein with ASB10. Definitions: integration defined as following: An operation used in calculus whereby the integral of a function is determined.. p75TNFR defined as following: Human TNFRSF1B wild-type allele is located within 1p36.3-p36.2 and is approximately 42 kb in length. This allele, which encodes tumor necrosis factor receptor superfamily member 1B protein, plays a role in the mediation of tumor necrosis factor-alpha signaling.. Alu element defined as following: The Alu sequence family (named for the restriction endonuclease cleavage enzyme Alu I) is the most highly repeated interspersed repeat element in humans (over a million copies). It is derived from the 7SL RNA component of the SIGNAL RECOGNITION PARTICLE and contains an RNA polymerase III promoter. Transposition of this element into coding and regulatory regions of genes is responsible for many heritable diseases.. exons defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.. human defined as following: Members of the species Homo sapiens..", "label": "yes"} {"id": "converted_844", "sentence1": "Is there a genome-wide technique for the detection of R-loop formation?", "sentence2": "Genome-wide analysis of fragile sites by chromatin immunoprecipitation (ChIP) and microarray (ChIP-chip) of phosphorylated H2A in these mutants supported a transcription-dependent mechanism of DNA damage characteristic of R loops, We have used a bisulfite-sensitivity assay to demonstrate genome-wide increase in the occurrence of RNA-DNA hybrids (R-loops), including from antisense and read-through transcripts, in a nusG missense mutant defective for Rho-dependent termination., The results demonstrate a key function of FACT in the resolution of R-loop-mediated transcription-replication conflicts, likely associated with a specific chromatin organization., Previous work revealed that GC skew and R-loop formation associate with a core set of unmethylated CpG island (CGI) promoters in the human genome[SEP]Relations: histone H2A acetylation has relations: bioprocess_protein with TRRAP, bioprocess_protein with TRRAP, bioprocess_protein with NAA40, bioprocess_protein with NAA40, bioprocess_protein with EP400, bioprocess_protein with EP400. promoter clearance from RNA polymerase I promoter has relations: bioprocess_bioprocess with promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript, bioprocess_bioprocess with promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript, bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance during DNA-templated transcription. Definitions: H2A defined as following: Slightly lysine rich histone. One of four histones assembled into a nucleosomal core octamer. Various posttranslationally modified forms and variants exist. Combines with histone H2B in a heterodimer; two H2A/H2B dimers are incorporated in the nucleosomal octamer.. FACT defined as following: A non-profit corporation co-founded by the International Society for Cellular Therapy and the American Society of Blood and Marrow Transplantation for the purposes of voluntary inspection and accreditation in the field of cellular therapy. Founded in 1996, FACT establishes standards for high quality medical and laboratory practice in cellular therapies. FACT Standards are evidence-based requirements set by world-renowned experts vested in the improvement and progress of cellular therapy.. promoters defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. mutants defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. R-loops defined as following: An RNA-DNA hybrid structure formed when newly transcribed RNA remains bound to its DNA template. Stability of R-loops may play a role in GENETIC INSTABILITY.. R-loop defined as following: An RNA-DNA hybrid structure formed when newly transcribed RNA remains bound to its DNA template. Stability of R-loops may play a role in GENETIC INSTABILITY..", "label": "yes"} {"id": "converted_360", "sentence1": "Have thyronamines effects on fat tissue?", "sentence2": "In conclusion, trace amines and thyronamines are negative inotropic agents., Their in vivo administration induces effects opposite to those induced by thyroid hormone, including lowering of body temperature.[SEP]Relations: response to thyroid hormone has relations: bioprocess_protein with GBA, bioprocess_protein with GBA, bioprocess_bioprocess with response to thyroxine, bioprocess_bioprocess with response to thyroxine, bioprocess_protein with SLC26A5, bioprocess_protein with SLC26A5, bioprocess_protein with SLC34A1, bioprocess_protein with SLC34A1, bioprocess_protein with HPN, bioprocess_protein with HPN. Definitions: thyroid hormone defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs.. fat tissue defined as following: Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white..", "label": "no"} {"id": "converted_4283", "sentence1": "Is AZD9668 a VEGF mRNA drug?", "sentence2": "AZD9668, a neutrophil elastase inhibitor, plus ongoing budesonide/formoterol in patients with COPD., AZD9668 is a reversible and selective inhibitor of NE, well tolerated at doses of 60 mg bid during Phase I/IIa development.[SEP]Relations: ELANE has relations: protein_protein with AZU1, protein_protein with AZU1, drug_protein with Pegfilgrastim, drug_protein with Pegfilgrastim, protein_protein with NOTCH2NLA, protein_protein with NOTCH2NLA, drug_protein with Mdl 101,146, drug_protein with Mdl 101,146. chronic obstructive pulmonary disease has relations: disease_protein with MIR218-2, disease_protein with MIR218-2. Definitions: bid defined as following: Two times per day, at unspecified times.. neutrophil elastase defined as following: This gene plays a role in innate host defense.. COPD defined as following: A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.. VEGF defined as following: Human VEGFA wild-type allele is located within 6p12 and is approximately 16 kb in length. This allele, which encodes vascular endothelial growth factor A protein, plays a role in several processes related to vasculature function, including angiogenesis. The allele is also involved in endothelial cell growth cell migration and apoptotic inhibition..", "label": "no"} {"id": "converted_2802", "sentence1": "Does gepotidacin activate bacterial topoisomerase?", "sentence2": "GSK2140944 is a novel bacterial topoisomerase inhibitor in development for the treatment of bacterial infections.[SEP]Relations: Recurrent bacterial infections has relations: disease_phenotype_positive with purine nucleoside phosphorylase deficiency, disease_phenotype_positive with purine nucleoside phosphorylase deficiency, disease_phenotype_positive with chromomycosis, disease_phenotype_positive with chromomycosis, disease_phenotype_positive with adenosine deaminase deficiency, disease_phenotype_positive with adenosine deaminase deficiency, disease_phenotype_positive with pancytopenia due to IKZF1 mutations, disease_phenotype_positive with pancytopenia due to IKZF1 mutations, disease_phenotype_positive with Chediak-Higashi syndrome, disease_phenotype_positive with Chediak-Higashi syndrome. Definitions: bacterial infections defined as following: Infections by bacteria, general or unspecified..", "label": "no"} {"id": "converted_1913", "sentence1": "Is avanafil indicated for treatment of erectile dysfunction?", "sentence2": "CONTEXT: Avanafil (AVA) is used in the treatment of erectile dysfunction, but is reported for its poor aqueous solubility. , BACKGROUND: Phosphodiesterase 5 inhibitors (PDE5-Is) sildenafil, vardenafil, tadalafil and the recently approved avanafil represent the first-line choice for both on-demand and chronic treatment of erectile dysfunction (ED). , A survey on the experience of 136 Italian urologists in the treatment of erectile dysfunction with PDE5 inhibitors and recommendations for the use of Avanafil in the clinical practice., Efficacy of Avanafil 15 Minutes after Dosing in Men with Erectile Dysfunction: A Randomized, Double-Blind, Placebo Controlled Study., PURPOSE: We examined the therapeutic effects of avanafil 15 minutes after dosing in men with mild to severe erectile dysfunction., Sildenafil, vardenafil, tadalafil and avanafil are FDA approved drugs in market as PDE5 inhibitors for treating erectile dysfunction., CONCLUSION: Avanafil along with the other PDE5Is has shown to be a safe and effective oral treatment for ED, with avanafil's possible place in therapy for patients who want an on-demand option or as an alternative in patients who experience visual disturbances with the other agents., Avanafil (STENDRA™, SPEDRA™, Zepeeed™) is an oral phosphodiesterase type 5 inhibitor indicated for the treatment of erectile dysfunction., In a 12-week, randomized, double-blind, placebo-controlled, multicentre trial in patients with erectile dysfunction, avanafil 50, 100 and 200 mg recipients had significantly greater improvements from baseline than placebo recipients in mean international index of erectile dysfunction-erectile function domain scores and in successful vaginal penetration and sexual intercourse attempts (coprimary endpoints)., Avanafil for the treatment of erectile dysfunction. An updated review., Selectivity of avanafil, a PDE5 inhibitor for the treatment of erectile dysfunction: implications for clinical safety and improved tolerability., A randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of avanafil in subjects with erectile dysfunction., Avanafil, a potent and highly selective phosphodiesterase-5 inhibitor for erectile dysfunction., Avanafil, a highly selective phosphodiesterase type 5 inhibitor for erectile dysfunction, shows good safety profiles for retinal function and hemodynamics in anesthetized dogs., Cumulative data suggest that avanafil has a promising pharmacological profile for erectile dysfunction., These findings suggest that intracavernosal administration of avanafil might be beneficial for the treatment of erectile dysfunction in patients with T2DM., An open-label, long-term evaluation of the safety, efficacy and tolerability of avanafil in male patients with mild to severe erectile dysfunction., The effect of intracavernosal avanafil, a newer phosphodiesterase-5 inhibitor, on neonatal type 2 diabetic rats with erectile dysfunction., A phase 3, placebo controlled study of the safety and efficacy of avanafil for the treatment of erectile dysfunction after nerve sparing radical prostatectomy., Avanafil is a potent selective phosphodiesterase type 5 (PDE5) inhibitor newly developed for treating erectile dysfunction (ED)., Adverse events most commonly reported with avanafil treatment were headache, nasopharyngitis, flushing, and sinus congestion.Avanafil was safe and effective for treating erectile dysfunction in men with diabetes and was effective as early as 15 minutes and more than 6 hours after dosing, Avanafil (STENDRA™, SPEDRA™, Zepeeed™) is an oral phosphodiesterase type 5 inhibitor indicated for the treatment of erectile dysfunction, Avanafil is rapidly absorbed after oral administration, with a median time to maximum plasma concentration of 30 to 45 min. In a 12-week, randomized, double-blind, placebo-controlled, multicentre trial in patients with erectile dysfunction, avanafil 50, 100 and 200 mg recipients had significantly greater improvements from baseline than placebo recipients in mean international index of erectile dysfunction-erectile function domain scores and in successful vaginal penetration and sexual intercourse attempts (coprimary endpoints), A phase II, single-blind, randomized, crossover evaluation of the safety and efficacy of avanafil using visual sexual stimulation in patients with mild to moderate erectile dysfunction, To evaluate the safety, efficacy and time course of three doses of avanafil (50 mg, 100 mg and 200 mg) compared with sildenafil 50 mg or placebo, given in conjunction with visual sexual stimulation (VSS) videos in men with mild to moderate erectile dysfunction (ED).Male patients, 35-70 years of age, with mild to moderate ED of ≥6 months duration, were included in the study, Avanafil for erectile dysfunction, To review the pharmacology, pharmacokinetics, safety, and efficacy of avanafil and evaluate relevant clinical trial data.A MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google Scholar searches (1966 to July 2013) were conducted using the key words: avanafil, erectile dysfunction, and phosphodiesterase type 5 (PDE5) inhibitor.Articles evaluating avanafil for erectile dysfunction (ED) published in English and using human subjects were selected, In trials in patients with erectile dysfunction in association with diabetes mellitus, and after nerve-sparing radical prostatectomy, avanafil 100 or 200 mg was significantly more efficacious than placebo for primary and most secondary endpoints, However, the potentiating effect of avanafil at 1 mg/kg was significantly weaker than that of sildenafil (p <0.05).Data suggest that avanafil has a favorable safety profile for erectile dysfunction, which is attributable to its high inhibitory selectivity for phosphodiesterase type 5 against type 6 (retina) and 1 (vessels, etc), respectively, and its short acting pharmacodynamic property.