{"original_question": "Is the monoclonal antibody Trastuzumab (Herceptin) of potential use in the treatment of prostate cancer?", "id": "converted_0", "sentence1": "Is the monoclonal antibody Trastuzumab (Herceptin) of potential use in the treatment of prostate cancer?", "sentence2": "Herceptin is widely used in treating Her2-overexpressing breast cancer. However, the application of Herceptin in prostate cancer is still controversial. Our data demonstrate that Re-188-labeled Herceptin effectively inhibited the growth of DU145 cells compared to the Herceptin- and Re-188-treated cohorts. This implies that targeting Her2 by both radio- and immuno- therapy might be a potential strategy for treating patients with androgen-independent prostate cancer. epidermal growth factor receptor (EGFR) family members are potential targets for therapy using extra-cellular domain receptor binding agents, such as the antibodies trastuzumab and cetuximab  there were tendencies for upregulation of HER2, increased co-expression of EGFR and HER2 and downregulation of HER3 in the prostate cancer lymph node metastases in comparison to the primary tumors.  We performed a comparative analysis in vitro and in vivo of the antitumor effects of three different antibodies targeting different epitopes of ErbB2: Herceptin (trastuzumab), 2C4 (pertuzumab) and Erb-hcAb (human anti-ErbB2-compact antibody), a novel fully human compact antibody produced in our laboratory. Herein, we demonstrate that the growth of both androgen-dependent and independent prostate cancer cells was efficiently inhibited by Erb-hcAb. The antitumor effects induced by Erb-hcAb on some cell lines were more potent than those observed for either Herceptin or 2C4. These findings suggest that a systemic delivery of 212Pb-trastuzumab could             be an effective modality for management of advanced human prostate cancer. Human epidermal growth factor receptor type 2 (HER2) overexpression supports proliferation of androgen-independent prostate cancer (PC) Radiolabeled ABY-025 Affibody molecule provides higher contrast in imaging of HER2-expressing PC xenografts than radiolabeled trastuzumab.  These studies indicate that dual EGFR/HER2 inhibition, administered together with AWT, sensitize prostate cancer cells to apoptosis during AWT The overall goal of these studies is to determine whether dual inhibition of the receptor tyrosine kinases epidermal growth factor receptor (EGFR) and HER2 would prolong the effectiveness of this treatment in prostate cancer.  The expression of HER2 was demonstrated and quantified in all three tested prostate cancer cell-lines. Such features would definitely favor the use of radiometal labels for trastuzumab and, most likely, for affibody molecules our data demonstrate that Her2 plays an important role in the support of AR protein stability in the transition of androgen requirement in prostate cancer cells. We hope these findings will provide novel insight into the treatment of hormone-refractory prostate cancer. These two cell lines exhibited distinct responses to Her2 activation (by heregulin treatment) on Her2 phosphorylation and Her2 inhibition (by AG825 or Herceptin treatments) on proliferation  While prostate cancers that express high levels of HER-2 are resistant to the killing effects of trastuzumab, they can be targeted for selective gene expression and destruction by lentiviruses with envelope proteins engineered to bind to this therapeutic antibody Overexpression of ErbB-2 and EGFR has been associated with aggressive disease and poor patient prognosis in a range of human tumour types (e.g. breast, lung, ovarian, prostate Various approaches have been developed to target the ErbB signalling pathways including monoclonal antibodies (trastuzumab/Herceptin The data from these in vitro and in vivo studies supported advancement of radiolabeled trastuzumab into two clinical studies Tumor targeting was evaluated in mice bearing subcutaneous (s.c.) xenografts of colorectal, pancreatic, ovarian, and prostate carcinomas. we found that although prostate cancers that express high levels of HER-2 are resistant to the killing effects of trastuzumab, they can be targeted for selective gene expression and destruction by viruses with envelope proteins engineered to bind this antibody detection of prostate cancer (PCa) and advances in hormonal and chemotherapy treatments have provided great clinical benefits to patients with early stages of the disease. MAbs directed to established targets include those approved for other solid tumors, including anti-human epidermal growth factor receptor-2 (HER2) MAb trastuzumab We conclude that Her2/neu expression in the peripheral blood mononuclear cell fraction of prostate cancer patients is frequent and therefore this assay may potentially be useful to detect the presence of micrometastatic disease in men with prostate cancer and for monitoring patients enrolled in trastuzumab-based therapeutic protocols. This study suggests that the docetaxel/trastuzumab combination may prove an effective therapeutic approach for HER2-expressing hormone-refractory prostate cancer. there was no significant difference in antimetastatic activity between the emulsion and the immunoemulsion despite the affinity of the immunoemulsion towards the HER2 receptor.  a targeted drug delivery system based on cationic emulsion covalently linked to anti-HER2 monoclonal antibody (Herceptin), in a well-established in vivo pharmacologic model of metastatic prostate cancer that overexpresses the HER2 receptor The finding of strong, consistent HER-2/neu expression in ACBCC suggests that treatment with Herceptin (trastuzumab) may be effective in patients with this rare tumour. Although HER2 can be over-expressed in prostate cancer, there is no clinical data to support the use of trastuzumab for prostate cancer patients. whereas the effect of the trastuzumab-RT combination was inferior to that predicted by the individual effects. HER 1-2 targeting of hormone-refractory prostate cancer by ZD1839 and trastuzumab Trastuzumab (Herceptin) as a single agent demonstrated poor efficacy in treating HRPC. To investigate the efficacy and toxicity of the antibody to the HER-2/neu receptor (trastuzumab, Herceptin) in the treatment of advanced hormone-refractory prostate cancer (HRPC) Conclusions regarding the predictive value of HER-2 status on outcome after trastuzumab-based therapy were not reached and were only drawn after larger-scale screening efforts.  rastuzumab plus docetaxel in HER-2/neu-positive prostate carcinoma clinical trials are currently in progress in patients with prostate cancer testing novel agents that selectively interfere with these receptors, such as trastuzumab, ytotoxicity of human prostate cancer cell lines in vitro and induction of apoptosis using 213Bi-Herceptin alpha-conjugate The clinical interpretation of c-erbB-2 abnormalities should reflect the complexity of c-erbB-2 mediated regulatory pathway and explain why tumours with overexpression/amplification of c-erbB-2 very often do not respond to therapy using Herceptin HER-2 overexpression also has been reported in up to 60% of patients with hormone-refractory prostate carcinoma (HRPC) and was correlated with shortened survival Unlike breast carcinoma and contrary to prior reports, HER-2 overexpression by IHC in archival prostate tissue from patients who eventually developed hormone-refractory disease was infrequent. There did not appear to be any correlation between HER-2 overexpression by IHC and shed HER-2 antigen levels in serum by ELISA in this tumor type. Further development of trastuzumab for the treatment of patients with metastatic prostate carcinoma is not feasible until more reliable and practical methods of sampling metastatic disease are developed to identify patients with HER-2 positive tumors. the expression of ERBB2 in prostate cancer is relatively low, and is not altered during disease progression. Thus, it is unlikely that treatment modalities relying on the overexpression of ERBB2 gene will be useful in treating prostate cancer. A phase I study was designed to evaluate docetaxel/estramustine plus trastuzumab, a humanized monoclonal antibody that binds to the HER2 receptor, in patients with metastatic androgen-independent prostate cancer (AIPC) Laboratory evidence also supports the clinical evaluation of docetaxel-based combinations that include agents such as trastuzumab and/or estramustine trastuzumab, a monoclonal antibody binding to the HER2 receptor; immunotoxin conjugates use an antibody directed against EGFR joined to a cell toxin. All are in clinical trials for a number of cancers, including prostate cancer we investigated the antitumor efficacy of Herceptin, a new recombinant humanized anti-HER2/neu antibody, which exhibits cytostatic activity on breast and prostate cancer cells that overexpress the HER2 oncogene. trastuzumab was found to have additive and synergistic effects with some chemotherapeutic agents ER-2/neu as a therapeutic target in non-small cell lung cancer, prostate cancer in these prostate cancer model systems, Herceptin alone has clinical activity only in the androgen-dependent tumor and has at least an additive effect on growth, anti-HER2 receptor monoclonal antibody Herceptin significantly enhanced growth inhibition of the MDA PCa 2a cells.[SEP]Relations: Trastuzumab has relations: indication with HER2 positive breast carcinoma, indication with HER2 positive breast carcinoma, drug_drug with Daclizumab, drug_drug with Daclizumab, drug_drug with Tepoxalin, drug_drug with Tepoxalin, drug_drug with Golimumab, drug_drug with Golimumab, drug_drug with Ascrinvacumab, drug_drug with Ascrinvacumab. Definitions: 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.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. lentiviruses defined as following: A genus of the family RETROVIRIDAE consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species.. 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.. 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.. ERBB2 gene defined as following: The erbB-2 gene is a proto-oncogene that codes for the erbB-2 receptor (RECEPTOR, ERBB-2), a protein with structural features similar to the epidermal growth factor receptor. Its name originates from the viral oncogene homolog (v-erbB) which is a truncated form of the chicken erbB gene found in the avian erythroblastosis virus. Overexpression and amplification of the gene is associated with a significant number of adenocarcinomas. The human c-erbB-2 gene is located at 17q21.2.. breast carcinoma 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.. pertuzumab defined as following: A humanized recombinant monoclonal antibody directed against the extracellular dimerization domain of the HER-2 tyrosine kinase receptor. Binding of the antibody to the dimerization domain of the HER-2 tyrosine kinase receptor protein directly inhibits the ability of the HER-2 tyrosine kinase receptor protein (the most common pairing partner) to dimerize with other HER tyrosine kinase receptor proteins; inhibiting receptor protein dimerization prevents the activation of HER signaling pathways, resulting in tumor cell apoptosis. (NCI04). 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). c-erbB-2 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.. heregulin defined as following: A growth factor of the EGF family that induces growth and differentiation of epithelial, glial and muscle cells in culture. It binds the receptor erbB3 which will heterodimerize with HER-2/erbB2.. AG825 defined as following: A member of the tyrphostin family of tyrosine kinase inhibitors, which selectively inhibits HER2. (NCI). metastatic prostate carcinoma defined as following: A carcinoma that arises from the prostate gland and has spread to other anatomic sites.. prostate cancer defined as following: A primary or metastatic malignant tumor involving the prostate gland. The vast majority are carcinomas.. monoclonal antibodies defined as following: Antibodies produced by a single clone of cells.. 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.. 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.. docetaxel/estramustine defined as following: A regimen consisting of docetaxel and estramustine used for the treatment of metastatic hormone-refractory prostate cancer. Additional steroids such as dexamethasone or hydrocortisone may also be included in this regimen.. 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.. 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.. human defined as following: Members of the species Homo sapiens.. 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.. 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). 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.. ErbB defined as following: This gene is involved in the epidermal growth factor signal transduction pathway.. 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.. 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.. 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).. 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.. 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.. HRPC defined as following: Prostate carcinoma that grows and continues to spread despite the surgical removal of the testes or medical intervention to block androgen production.. HER3 defined as following: A cell surface protein-tyrosine kinase receptor that is specific for NEUREGULINS. It has extensive homology to and can heterodimerize with the EGF RECEPTOR and the ERBB-2 RECEPTOR. Overexpression of the erbB-3 receptor is associated with TUMORIGENESIS.. 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]. epitopes defined as following: Sites on an antigen that interact with specific antibodies.. 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.. 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.. primary tumors defined as following: A tumor at the original site of origin.. estramustine defined as following: A nitrogen mustard linked to estradiol, usually as phosphate; used to treat prostatic neoplasms; also has radiation protective properties.. metastatic disease defined as following: A tumor that has spread from its original (primary) site of growth to another site, close to or distant from the primary site. Metastasis is characteristic of advanced malignancies, but in rare instances can be seen in neoplasms lacking malignant morphology..", "label": "yes"}
{"original_question": "Are ultraconserved elements often transcribed?", "id": "converted_1", "sentence1": "Are ultraconserved elements often transcribed?", "sentence2": "Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs) Our data gives a first glimpse of a novel functional hypoxic network comprising protein-coding transcripts and noncoding RNAs (ncRNAs) from the T-UCRs category Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores. We refer to the elements as 'Olfactores conserved non-coding elements' We used a custom microarray to assess the levels of UCE transcription during mouse development and integrated these data with published microarray and next-generation sequencing datasets as well as with newly produced PCR validation experiments. We show that a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand. Although the nature of these transcripts remains a mistery, our meta-analysis of RNA-Seq datasets indicates that they are unlikely to be short RNAs and that some of them might encode nuclear transcripts Our data shows that the concurrent presence of enhancer and transcript function in non-exonic UCE elements is more widespread than previously shown. Moreover through our own experiments as well as the use of next-generation sequencing datasets, we were able to show that the RNAs encoded by non-exonic UCEs are likely to be long RNAs transcribed from only one DNA strand Short ultraconserved promoter regions delineate a class of preferentially expressed alternatively spliced transcripts The importance of other classes of non-coding RNAs, such as long intergenic ncRNAs (lincRNAs) and transcribed ultraconserved regions (T-UCRs) as altered elements in neoplasia, is also gaining recognition. Other ncRNAs, such as PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transcribed ultraconserved regions (T-UCRs) and large intergenic non-coding RNAs (lincRNAs) are emerging as key elements of cellular homeostasis. The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores. Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed. Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development. The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. In this report, we show that the Dlx-5/6 ultraconserved region is transcribed to generate an alternatively spliced form of Evf-1, the ncRNA Evf-2. These studies identify a critical role for TUC338 in regulation of transformed cell growth and of transcribed ultraconserved ncRNA as a unique class of genes involved in the pathobiology of HCC. Transcribed ultraconserved region (T-UCR) transcripts are a novel class of lncRNAs transcribed from ultraconserved regions (UCRs) The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed Other ncRNAs, such as PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transcribed ultraconserved regions (T-UCRs) and large intergenic non-coding RNAs (lincRNAs) are emerging as key elements of cellular homeostasis Transcribed ultraconserved region in human cancers. We show that a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand Although uc.338 is partially located within the poly(rC) binding protein 2 (PCBP2) gene, the transcribed ncRNA encoding uc.338 is expressed independently of PCBP2 and was cloned as a 590-bp RNA gene, termed TUC338 Moreover through our own experiments as well as the use of next-generation sequencing datasets, we were able to show that the RNAs encoded by non-exonic UCEs are likely to be long RNAs transcribed from only one DNA strand.[SEP]Relations: rRNA transcription has relations: bioprocess_protein with ANG, bioprocess_protein with ANG, bioprocess_bioprocess with plastid rRNA transcription, bioprocess_bioprocess with plastid rRNA transcription, bioprocess_bioprocess with mitochondrial rRNA transcription, bioprocess_bioprocess with mitochondrial rRNA transcription, bioprocess_bioprocess with ncRNA transcription, bioprocess_bioprocess with ncRNA transcription, bioprocess_bioprocess with nucleolar large rRNA transcription by RNA polymerase I, bioprocess_bioprocess with nucleolar large rRNA transcription by RNA polymerase I. Definitions: 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.. 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.. elements defined as following: Substances that comprise all matter. Each element is made up of atoms that are identical in number of electrons and protons and in nuclear charge but may differ in mass or number of neutrons.. vertebrates defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes.. 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). 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.. 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.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. 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.. sequences defined as following: The sequence of nucleotide residues along a DNA chain.. fraction defined as following: <p>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.</p>. transcripts defined as following: The initial RNA molecule produced by transcription..", "label": "yes"}
{"original_question": "Have Quantitative Trait Loci affecting splicing (splicing QTLs) been linked to disease?", "id": "converted_2", "sentence1": "Have Quantitative Trait Loci affecting splicing (splicing QTLs) been linked to disease?", "sentence2": "The spontaneously hypertensive rat (SHR) is a widely used rodent model of hypertension and metabolic syndrome. Previously we identified thousands of cis-regulated expression quantitative trait loci (eQTLs) across multiple tissues using a panel of rat recombinant inbred (RI) strains derived from Brown Norway and SHR progenitors. These cis-eQTLs represent potential susceptibility loci underlying physiological and pathophysiological traits manifested in SHR. We have prioritized 60 cis-eQTLs and confirmed differential expression between the parental strains by quantitative PCR in 43 (72%) of the eQTL transcripts. These colocalizing correlated cis-eQTLs (c3-eQTLs) are highly attractive as primary susceptibility loci for the colocalizing pQTLs. Furthermore, sequence analysis of the c3-eQTL genes identified single nucleotide polymorphisms (SNPs) that are predicted to affect transcription factor binding affinity, splicing and protein function. These SNPs, which potentially alter transcript abundance and stability, represent strong candidate factors underlying not just eQTL expression phenotypes, but also the correlated metabolic and physiological traits. In conclusion, by integration of genomic sequence, eQTL and QTT datasets we have identified several genes that are strong positional candidates for pathophysiological traits observed in the SHR strain. Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application.RESULTS: Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants.CONCLUSION: Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing. The six genes corresponded to rat and mouse quantitative trait loci (QTLs) that had shown associations with the common traits such as the well characterized MS and even tumor susceptibility. Our findings suggest that the six genes may play important roles in the pleiotropic effects on lipid metabolism and the MS, which increase the risk of Type 2 Diabetes and cardiovascular disease. The use of the multivariate phenotypes can be advantageous in identifying genetic risk factors, accounting for the pleiotropic effects when the multivariate phenotypes have a common etiological pathway. To elucidate mechanisms involved in multiple sclerosis (MS), we studied genetic regulation of experimental autoimmune encephalomyelitis (EAE) in rats, assuming a conservation of pathogenic pathways. In this study, we focused on Eae23, originally identified to regulate EAE in a (LEW.1AV1xPVG.1AV1)F2 cross. Our aim was to determine whether one or more genes within the 67 Mb region regulate EAE and to define candidate risk genes.METHODOLOGY/PRINCIPAL FINDINGS: We used high resolution quantitative trait loci (QTL) analysis in the 10th generation (G10) of an advanced intercross line (AIL) to resolve Eae23 into two QTLs that independently regulate EAE, namely Eae23a and Eae23b.[SEP]Relations: qualitative or quantitative defects of titin has relations: disease_disease with TTN-related myopathy, disease_disease with TTN-related myopathy, disease_disease with qualitative or quantitative protein defects in neuromuscular diseases, disease_disease with qualitative or quantitative protein defects in neuromuscular diseases, disease_disease with limb-girdle muscular dystrophy, disease_disease with limb-girdle muscular dystrophy, disease_disease with tibial muscular dystrophy, disease_disease with tibial muscular dystrophy. multiple sclerosis has relations: disease_disease with demyelinating disease, disease_disease with demyelinating disease. 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.. quantitative trait loci defined as following: Genetic loci associated with a quantitative trait.. single nucleotide polymorphisms defined as following: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.. rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. 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.. conservation defined as following: The maintenance of certain characteristics in an unchanged condition.. transcripts defined as following: The initial RNA molecule produced by transcription.. genotypes defined as following: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.. cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. 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.. 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.. 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). 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.. 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"}
{"original_question": "Is SLC22A3 expressed in the brain?", "id": "converted_3", "sentence1": "Is SLC22A3 expressed in the brain?", "sentence2": "The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission.  The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain. In agreement with this distribution, OCT3/Slc22a3-deficient mice show evidence of altered monoamine neurotransmission in the brain, with decreased intracellular content and increased turnover of aminergic transmitters. CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain.  CRT may be a key factor facilitating blood-to-brain guanidinoacetate transport in patients deficient in S-adenosylmethionine:guanidinoacetate N-methyltransferase, the creatine biosynthetic enzyme, resulting in cerebral accumulation of guanidinoacetate. CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain. CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Interestingly, BBB efflux transport of GCs, including guanidinoacetate and creatinine, is negligible, though the BBB has a variety of efflux transport systems for synthetic precursors of GCs, such as amino acids and neurotransmitters.  The organic cation transporter (OCT) 3 is widely expressed in various organs in humans, and involved in the disposition of many exogenous and endogenous compounds. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission. CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Several lines of evidence have suggested that OCT3 expressed in the brain plays an important role in the regulation of neurotransmission. The organic cation transporter 3 (OCT3; synonymous: extraneuronal monoamine transporter, EMT, Slc22a3) encodes an isoform of the organic cation transporters and is expressed widely across the whole brain. OCT2-OCT-3 display differential tissue distribution: OCT1 is predominantly found in liver of humans, and liver and kidney in rodents; OCT2 is most strongly expressed in both human and rodent kidney, whereas is OCT3 primarily expressed in placenta, but also more widely detected in various tissues, including brain and lung.[SEP]Relations: SLC22A3 has relations: anatomy_protein_present with heart, anatomy_protein_present with heart, anatomy_protein_present with colon, anatomy_protein_present with colon, cellcomp_protein with membrane, cellcomp_protein with membrane, anatomy_protein_present with kidney, anatomy_protein_present with kidney, anatomy_protein_present with intestine, anatomy_protein_present with intestine. 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.. organic cation transporter defined as following: Solute carrier family 22 member 1 (554 aa, ~61 kDa) is encoded by the human SLC22A1 gene. This protein is involved in bidirectional cation transport.. S-adenosylmethionine 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). BBB defined as following: Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.. GCs defined as following: Ceramide glucosyltransferase (394 aa, ~45 kDa) is encoded by the human UGCG gene. This protein is involved in the glycosylation of N-acylsphingosine.. OCT2 defined as following: This gene is involved in transcriptional activation and plays a role in mature B cell maintenance.. humans defined as following: Members of the species Homo sapiens.. OCT3 defined as following: This gene plays a role in early mammalian 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.. 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.. OCT1 defined as following: This gene plays a role in transcriptional activation and modulates immunoglobulin activity.. CSF 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.. rodents defined as following: A mammalian order which consists of 29 families and many genera.. Slc22a3 defined as following: This gene is involved in membrane potential-dependent transport of organic cations.. 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.. organic cation transporter 3 defined as following: Solute carrier family 22 member 3 (556 aa, ~61 kDa) is encoded by the human SLC22A3 gene. This protein is involved in mediating membrane potential-dependent transport of organic cations and may play a role in the disposition of cationic neurotoxins and neurotransmitters in the brain.. SLC22A3 defined as following: This gene is involved in membrane potential-dependent transport of organic cations..", "label": "yes"}
{"original_question": "Is alternative splicing of apoptotic genes playing a role in the response to DNA or mitochondrial damage?", "id": "converted_4", "sentence1": "Is alternative splicing of apoptotic genes playing a role in the response to DNA or mitochondrial damage?", "sentence2": "Apoptosis promoted by UV in cells lacking p53 is prevented when the change in AS of the apoptotic gene bcl-x is reverted, confirming the relevance of this mechanism. We demonstrate that E2F1 requires SC35 to switch the alternative splicing profile of various apoptotic genes such as c-flip, caspases-8 and -9 and Bcl-x, towards the expression of pro-apoptotic splice variants. Finally, we provide evidence that E2F1 upregulates SC35 in response to DNA-damaging agents and show that SC35 is required for apoptosis in response to these drugs. This analysis revealed that DNA damage resulted in changes in splicing activity that modified the splicing pattern of Fas, a key pro-apoptotic, p53-inducible death receptor. Bortezomib induces mitochondrial damage in native cells and also activates the UPR by splicing of Xbp-1 and induction of CHOP, which is significantly reduced by silencing of MUC4. The tumour-suppressor protein p53 is an important activator of apoptosis. Although p53-deficient cancer cells are less responsive to chemotherapy, their resistance is not complete, which suggests that other apoptotic pathways may exist. A p53-related gene, p73, which encodes several proteins as a result of alternative splicing, can also induce apoptosis. Induction of apoptosis was significantly reduced in P388/SPR cells, as indicated by minimal DNA fragmentation. Analysis of oncogenes regulating apoptotic cell death revealed a marked decrease of bcl-2 in combination with a moderate reduction of bax protein, but a striking overexpression of the long form of the bcl-X protein.[SEP]Relations: positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator has relations: bioprocess_bioprocess with positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage, bioprocess_bioprocess with positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage, bioprocess_bioprocess with regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator, bioprocess_bioprocess with regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator, bioprocess_protein with RPL26, bioprocess_protein with RPL26, bioprocess_bioprocess with positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator, bioprocess_bioprocess with positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator. mitochondrial matrix has relations: cellcomp_protein with AASS, cellcomp_protein with AASS. 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.. bax 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.. Bcl-x 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.. CHOP defined as following: A chemotherapy regimen consisting of cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine and prednisone used to treat both indolent and aggressive forms of non-Hodgkin lymphoma. (\"http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C9549\" NCI Thesaurus). 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.. SC35 defined as following: Human SRSF2 wild-type allele is located in the vicinity of 17q25.1 and is approximately 4 kb in length. This allele, which encodes serine/arginine-rich splicing factor 2 protein, is involved in the regulation of RNA splicing.. oncogenes 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.. 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.. E2F1 defined as following: Transcription factor E2F1 (437 aa, ~47 kDa) is encoded by the human E2F1 gene. This protein is involved in the regulation of apoptosis, gene transcription, cell cycle progression and cell proliferation.. modified defined as following: The act of alteration or modification; changed or altered in form or character.. MUC4 defined as following: Mucin-4 (2169 aa, ~232 kDa) is encoded by the human MUC4 gene. This protein is involved in receptor signaling, the modulation of cell-matrix adhesion, and in tumor progression.. 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.. 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.. c-flip defined as following: CASP8 and FADD-like apoptosis regulator (480 aa, ~55 kDa) is encoded by the human CFLAR gene. This protein plays a role in the inhibition of caspase-dependent apoptosis.. Xbp-1 defined as following: X-box binding protein 1 (261 aa, ~29 kDa) is encoded by the human XBP1 gene. This protein is a bZIP transcription factor that is involved in both the transcription of major histocompatibilty complex class II genes and the response to unfolded proteins and viral infection.. mitochondrial damage defined as following: Mitochondrial Damage involves any process that leads to dysfunction of mitochondria, whether by oxidative damage, mutation of mitochondrial DNA or other by means.. 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.. 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"}
{"original_question": "Is exonuclease Xrn1 a component of the P-bodies?", "id": "converted_5", "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' \u2192 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&apos;-3&apos; 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 &quot;P bodies,&quot; 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&apos;-3&apos; 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&apos;-3&apos; 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: DDX6 defined as following: This gene plays a role in the translation of mRNA encoded by genes involved in cell proliferation and malignant transformation.. 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.. 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.. 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.. cell lines defined as following: Established cell cultures that have the potential to propagate indefinitely.. 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.. TTP defined as following: Thrombotic thrombocytopenic purpura for which the cause is present from birth.. 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]. 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.. 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.. 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.. 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). 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.-. human defined as following: Members of the species Homo sapiens.. eukaryotic cells defined as following: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane.. miRNA 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.. 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.. 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). 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.. 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.. polysomes defined as following: A ribosome bound to mRNA that forms part of a polysome. [GOC:jl]. 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]. 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]. granules defined as following: A solid composed of small particles or grains.. 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.. 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.. 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.. 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.. regulatory proteins defined as following: Encoded by Regulatory Genes, Regulatory Proteins regulate or circumscribe the activity of many cellular functions.. 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.. argonaute proteins defined as following: A protein family that is comprised of the catalytic components of the RNA-induced silencing complex.. SNPs defined as following: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.. 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). 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"}
{"original_question": "Is there a package in R/bioconductor for classification of alternative splicing?", "id": "converted_6", "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: RNA-seq defined as following: A procedure that can determine the nucleotide sequence for all of the RNA transcripts in an individual.. 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.. 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"}
{"original_question": "Is intense physical activity associated with longevity?", "id": "converted_7", "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"}
{"original_question": "Have gnotobiotic animal models been used for the study of bowel disease?", "id": "converted_8", "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: 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.. 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.. 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.. L. reuteri defined as following: A species of gram-positive, rod-shaped LACTIC ACID bacteria found naturally in the human intestinal flora and BREAST MILK.. 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.. human defined as following: Members of the species Homo sapiens.. bowel disease defined as following: Pathological processes in any segment of the INTESTINE from DUODENUM to RECTUM..", "label": "yes"}
{"original_question": "Is it possible to detect survivin protein expression in normal human adult tissues?", "id": "converted_9", "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/\u03b3c(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: 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.. 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.. cell lines defined as following: Established cell cultures that have the potential to propagate indefinitely.. cancer defined as following: A malignant tumor at the original site of growth.. 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.. 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.. 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.. 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.. 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.. 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.. 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.. 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.. murine defined as following: Any of numerous species of small rodents belonging to the genus Mus and various related genera of the family Muridae.. 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.. 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.. telomerase defined as following: An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.. 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.. 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.. 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.. 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.. 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.. 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.. 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.. mitochondrial membrane defined as following: Either of the lipid bilayers that surround the mitochondrion and form the mitochondrial envelope. [GOC:mah, NIF_Subcellular:sao1045389829]. 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.. 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.. 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.. 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"}
{"original_question": "Is delayed enhancement documented in patients with non-ischemic dilated cardiomyopathy?", "id": "converted_10", "sentence1": "Is delayed enhancement documented in patients with non-ischemic dilated cardiomyopathy?", "sentence2": "Myocardial fibrosis was present in 30% of patients, the majority of which was mid-myocardial (63%).   DCM patients frequently have myocardial fibrosis detected on CE-CMR, the majority of which is mid-myocardial. Fifty (40%) patients showed myocardial DE, representing 12\u00b17% of LV mass. one case was dilated cardiomyopathy, in which the delayed enhancement was diffuse small midwall spots  In the dilated cardiomyopathy group, only seven (29%) patients showed delayed enhancement and its pattern was characterized by mid-wall, patchy or diffuse location. Patterns of delayed enhancement are different in dilated cardiomyopathy and ischemic cardiomyopathy, reflecting the presence of scarring or various degrees of fibrosis in left ventricular myocardium. The presence of subendocardial or transmural delayed enhancement at contrast-enhanced cardiovascular magnetic resonance allowed distinction between dilated cardiomyopathy and ischemic cardiomyopathy with high sensitivity (88%) and specificity (100%).[SEP]Relations: dilated cardiomyopathy has relations: disease_disease with non-familial dilated cardiomyopathy, disease_disease with non-familial dilated cardiomyopathy, disease_disease with left ventricular noncompaction, disease_disease with left ventricular noncompaction, disease_disease with syndrome associated with dilated cardiomyopathy, disease_disease with syndrome associated with dilated cardiomyopathy, disease_disease with qualitative or quantitative defects of beta-myosin heavy chain (MYH7), disease_disease with qualitative or quantitative defects of beta-myosin heavy chain (MYH7), disease_disease with intrinsic cardiomyopathy, disease_disease with intrinsic cardiomyopathy. Definitions: transmural defined as following: Passing through the wall of an organ or other bodily structure.. 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).. 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). 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.. fibrosis defined as following: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury..", "label": "yes"}
{"original_question": "Do lincRNAs play a role in human cancer?", "id": "converted_11", "sentence1": "Do lincRNAs play a role in human cancer?", "sentence2": "Long non-coding RNA H19 increases bladder cancer metastasis These data suggest that upregulated H19 enhances bladder cancer metastasis by associating with EZH2 and inhibiting E-cad expression lncRNA H19 is essential for human tumor growth Previous reports have demonstrated that HOTAIR associates with chromatin modifications in cooperation with the Polycomb complex PRC2, and promotes breast and colorectal cancer metastasis although the clinical significance of HOTAIR expression in HCC may not be as pronounced as that in breast and colorectal cancers, the current study demonstrates that HOTAIR expression is associated with HCC progression, warranting further studies. Long non-coding RNA HOTAIR is an independent prognostic marker for nasopharyngeal carcinoma progression and survival Long non-coding RNA influences radiosensitivity of colorectal carcinoma cell lines by regulating cyclin D1 expression Long non-coding RNA urothelial carcinoma associated 1 (UCA1) promotes human bladder cancer cell proliferation, but the underlying mechanism remains unknown UCA1 regulated cell cycle through CREB via PI3K-AKT dependent pathway in bladder cancer. Long non-coding RNA UCA1 regulated cell cycle distribution via CREB through PI3-K dependent pathway in bladder carcinoma cells overexpression of Yiya promotes cell cycle progression at the G1/S transition, therefore identifying Yiya as a cell-cycle-associated long non-coding RNA The long noncoding RNA HOTAIR has been reported as a poor prognostic biomarker in patients with breast cancer. The aim of the present study is to examine the expression pattern of HOTAIR in hepatocellular carcinoma (HCC) and its clinical significance as well as its biological role in tumor progression The high expression level of HOTAIR in HCC could be a candidate biomarker for predicting tumor recurrence in HCC patients who have undergone liver transplant therapy and might be a potential therapeutic target Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene A 42\u2009kb region on human chromosome 9p21 encodes for three distinct tumor suppressors, p16(INK4A), p14(ARF) and p15(INK4B), and is altered in an estimated 30-40% of human tumors These results advance our understanding of the role of lncRNA-LET as a regulator of hypoxia signaling and\u00a0offer new avenues for therapeutic intervention against cancer progression. Silencing MALAT1 is a potential novel therapeutic approach for this cancer.[SEP]Relations: Protein S human has relations: drug_drug with Linsidomine, drug_drug with Linsidomine, drug_drug with Ximelagatran, drug_drug with Ximelagatran, drug_drug with Melagatran, drug_drug with Melagatran, drug_drug with Vinblastine, drug_drug with Vinblastine, drug_drug with Letaxaban, drug_drug with Letaxaban. Definitions: 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). 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.. H19 defined as following: Maternally expressed exclusively and developmentally regulated human putative tumor suppressor H19 Gene encodes H19 Imprinted Maternal Untranslated mRNA. Expression in developing skeletal and smooth muscles correlates with specific differentiation events. It accumulates during skeletal muscle development with maximal adult expression and correlates with the nonproliferative, actin-positive muscle cell phenotype. Loss of H19 expression may be involved in Wilms tumorigenesis. (NCI). cancer defined as following: A malignant tumor at the original site of growth.. tumor suppressors 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.. MALAT1 defined as following: Metastasis-associated lung adenocarcinoma transcript 1 (~8.7 kb) is encoded by the human MALAT1 gene. This non-coding RNA may play a role in cancer and metastasis.. human defined as following: Members of the species Homo sapiens.. 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.. 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.. HOTAIR defined as following: This gene plays a role in the repression of HOXD gene expression.. 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.. 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.. 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.. bladder cancer defined as following: A primary or metastatic malignant neoplasm involving the bladder.. 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.. 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.. hypoxia defined as following: A disorder characterized by a decrease in the level of oxygen in the body.. 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.. 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.. 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.. Long non-coding RNA 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.. 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.. 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..", "label": "yes"}
{"original_question": "Is the Prostate- Specific Antigen (PSA) test relevant only for prostate cancer?", "id": "converted_12", "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.. 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-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.. cancer death defined as following: A death attributed to the progression of a cancer-related pathologic condition.. 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.. 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.. prostate cancer defined as following: A primary or metastatic malignant tumor involving the prostate gland. The vast majority are carcinomas..", "label": "no"}
{"original_question": "Is insulin-like growth factor-I (IGF-I) able to affect tendon protein synthesis in classic Ehlers-Danlos syndrome patients?", "id": "converted_13", "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: connective tissue has relations: anatomy_protein_present with IGF1R, anatomy_protein_present with IGF1R, anatomy_protein_present with IGF1, anatomy_protein_present with IGF1, anatomy_protein_present with IGFBP4, anatomy_protein_present with IGFBP4, anatomy_protein_present with FGFR4, anatomy_protein_present with FGFR4, anatomy_protein_present with EGFL7, anatomy_protein_present with EGFL7. Definitions: 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.. 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.. 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"}
{"original_question": "Is there any functional association during viral replication between flaviviridae viral RNA depended RNA polymerase and viral helicase?", "id": "converted_14", "sentence1": "Is there any functional association during viral replication between flaviviridae viral RNA depended RNA polymerase and viral helicase?", "sentence2": "Several labs have obtained evidence for a protein complex that involves many of the nonstructural (NS) proteins encoded by the virus. NS3, NS4A, NS4B, NS5A, and NS5B appear to interact structurally and functionally. In this study, we investigated the interaction between the helicase, NS3, and the RNA polymerase, NS5B. Pull-down experiments and surface plasmon resonance data indicate a direct interaction between NS3 and NS5B that is primarily mediated through the protease domain of NS3. This interaction reduces the basal ATPase activity of NS3. However, NS5B stimulates product formation in RNA unwinding experiments under conditions of excess nucleic acid substrate. When the concentrations of NS3 and NS5B are in excess of nucleic acid substrate, NS5B reduces the rate of NS3-catalyzed unwinding. Under pre-steady-state conditions, in which NS3 and substrate concentrations are similar, product formation increased in the presence of NS5B. The increase was consistent with 1:1 complex formed between the two proteins. A fluorescently labeled form of NS3 was used to investigate this interaction through fluorescence polarization binding assays. Results from this assay support interactions that include a 1:1 complex formed between NS3 and NS5B. Contradictory results have been reported regarding NS3 in RNA synthesis. To investigate the effect of NS3 on classical swine fever virus (CSFV) NS5B RNA-dependent RNA polymerase activity (RdRp) activity and NS3-NS5B interaction, RdRp reactions, GST-pull-down assays and co-immunoprecipitation analyses containing NS5B and either of NS3 protein and the different truncated NS3 mutants were performed, respectively. We found that NS3 stimulated NS5B RdRp activity in a dose-dependent manner by binding to NS5 through a NS3 protease domain. Furthermore, mapping important regions of the NS3 protease domain was carried out by deletion mutagenesis, associated with RdRp reactions, GST-pull-down assays and co-immunoprecipitation analyses. Results showed that stimulation of CSFV NS5B RdRp activity was obtained by NS3 binding to NS5B through a 31-amino acid fragment at the N-terminal end of NS3 protease domain, which mediated a specific NS3-NS5B interaction. The protocols detailed in this unit are used to purify three recombinant enzymes that are widely used in HCV research: the HCV NS3 protease domain, the helicase domain as an NS3+NS4A complex, and the NS5B RNA-dependent RNA polymerase. The active enzymes are purified to homogeneity by two-column chromatography to support a screening program for HCV inhibitors. Among potential targets are viral entry factors, including scavenger receptor type B1 (SR-B1) and CD81, as well as neutralizing antibodies against the viral glycoproteins. Popular targets related to translation and replication are the NS3/4A protease (inhibited by telaprevir and boceprevir) and the NS5B polymerase, as well as the NS2/3 autoprotease, the NS3 helicase, and nonenzymatic targets such as NS4B and NS5A proteins.  The NS3 helicase domain competes with NS3 full-length for NS5 RdRp binding, with a K(d.) of 2.5\u03bcM. Since NS3 and NS5 are required for DENV replication, this fascile assay could be used to screen for non-nucleoside, allosteric inhibitors that disrupt the interaction between the two proteins.[SEP]Relations: RNA-directed DNA polymerase activity has relations: molfunc_molfunc with DNA polymerase activity, molfunc_molfunc with DNA polymerase activity, molfunc_protein with ERVK-11, molfunc_protein with ERVK-11, molfunc_protein with ERVK-8, molfunc_protein with ERVK-8, molfunc_protein with ERVK-10, molfunc_protein with ERVK-10, molfunc_protein with ERVK-7, molfunc_protein with ERVK-7. Definitions: neutralizing antibodies defined as following: Antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent, usually a virus.. boceprevir defined as following: An orally bioavailable, synthetic tripeptide inhibitor of the nonstructural protein 3 and 4A complex (NS3/NS4A), with potential activity against hepatitis C virus (HCV) genotype 1. Upon administration, boceprevir reversibly binds to the active center of the HCV NS3/NS4A and prevents NS3/NS4A protease-mediated polyprotein maturation. This disrupts the processing of viral proteins and the formation of a viral replication complex, which inhibits viral replication in HCV genotrype 1-infected host cells. NS3, a serine protease, is essential for the proteolytic cleavages within the HCV polyprotein and plays a key role during HCV viral RNA replication. NS4A is an activating factor for NS3. HCV is a small, enveloped, single-stranded RNA virus belonging to the Flaviviridae family.. deletion mutagenesis defined as following: Mutagenesis where the mutation is caused by the loss of DNA sequences within a gene. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro.. NS5 defined as following: Noonan syndrome caused by autosomal dominant mutation(s) in the RAF1 gene, encoding RAF proto-oncogene serine/threonine-protein kinase.. ATPase defined as following: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.. NS3 defined as following: Noonan syndrome caused by autosomal dominant mutation(s) in the KRAS gene, encoding GTPase KRas.. 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). nucleic acid defined as following: High molecular weight polymers containing a mixture of purine and pyrimidine nucleotides chained together by ribose or deoxyribose linkages.. 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).. 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.. 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.. protease domain defined as following: The portion of a proteolytic protein which causes hydrolysis and cleavage of other protein polypeptides.. SR-B1 defined as following: Human SCARB1 wild-type allele is located in the vicinity of 12q24.31 and is approximately 106 kb in length. This allele, which encodes scavenger receptor class B member 1 protein, plays a role in both binding and import of lipids and lipoproteins.. domain defined as following: A taxonomic category above that of Kingdom.. telaprevir defined as following: An orally available peptidomimetic small molecule with activity against hepatitis C virus (HCV). Telaprivir is a selective protease inhibitor that targets the viral HCV NS3-4A serine protease and disrupts processing of viral proteins and formation of a viral replication complex.. 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]. 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.. viral RNA defined as following: Ribonucleic acid that makes up the genetic material of viruses..", "label": "yes"}
{"original_question": "Are psammoma bodies characteristic to meningiomas?", "id": "converted_15", "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: psammomatous meningioma has relations: disease_disease with meningioma (disease), disease_disease with meningioma (disease), disease_protein with PTEN, disease_protein with PTEN, disease_protein with NF2, disease_protein with NF2, disease_protein with CSTB, disease_protein with CSTB, disease_protein with SMO, disease_protein with SMO. Definitions: 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.. calculi defined as following: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones.. 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.. 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.. 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).. Psammoma defined as following: A WHO grade I meningioma characterized by the presence of psammoma bodies that predominate over the meningeal cells.. 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). vimentin defined as following: OBSOLETE. A type of intermediate filament. [ISBN:0716731363]. 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.. cytoplasmic membranes defined as following: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.. 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). human defined as following: Members of the species Homo sapiens.. 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.. 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.. Calcification defined as following: Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.. tissue culture 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.. tumor tissue defined as following: A tumor sample, or entire tumor that is removed for microscopic examination.. 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.. 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.. membrane defined as following: A device that is made from or resembles a thin flexible sheet of material.. tumor cells defined as following: Cells of, or derived from, a tumor.. 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.. 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.. 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.. 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.. 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.. 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.. transitional meningioma defined as following: A WHO grade I meningioma characterized by the coexistence of meningothelial cells and fibrous architectural patterns.. fibroblastic meningioma defined as following: A WHO grade I meningioma characterized by the presence of spindle cells that form bundles in a collagen matrix.. meningioma defined as following: A grade I, slowly growing meningioma. Only a minority of tumors recur following complete resection.. 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.. 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]. 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]. PTC defined as following: The evaluation of the liver and biliary tree using a contrast agent injected directly into the liver.. vesicles defined as following: An abnormal fluid-filled cleft (e.g. as in the epidermis) or membrane-bound space.. capillaries defined as following: The minute vessels that connect arterioles and venules..", "label": "yes"}
{"original_question": "Does the histidine-rich Ca-binding protein (HRC) interact with triadin?", "id": "converted_16", "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.. 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.. cytoplasmic domain defined as following: The part of a transmembrane protein which projects into the cytoplasm.. 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.. monoclonal antibodies defined as following: Antibodies produced by a single clone of cells.. 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]. I-band defined as following: A region of a sarcomere that appears as a light band on each side of the Z disc, comprising a region of the sarcomere where thin (actin) filaments are not overlapped by thick (myosin) filaments; contains actin, troponin, and tropomyosin; each sarcomere includes half of an I band at each end. [ISBN:0321204131]. 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.. 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.. 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.. 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.. 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]. transmembrane protein defined as following: A protein that is an integral membrane protein with a transmembrane region.. 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.. 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.. 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.. muscle tissues defined as following: Contractile tissue that produces movement in animals.. 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"}
{"original_question": "Is oxalate renal excretion increased after bariatric surgery?", "id": "converted_17", "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: citrate defined as following: The determination of the amount of citrate present in a sample.. oxalate defined as following: A salt or ester of oxalic acid.. Hyperoxaluria defined as following: Excretion of an excessive amount of OXALATES in the urine.. calcium defined as following: A dietary supplement containing the mineral calcium.. 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.. Malabsorption defined as following: General term for a group of MALNUTRITION syndromes caused by failure of normal INTESTINAL ABSORPTION of nutrients..", "label": "yes"}
{"original_question": "Is the length of the poly(A) tail involved in human disease?", "id": "converted_18", "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.. 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.. 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.. 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"}
{"original_question": "Are patients with marfan syndrome at increased risk of arrhythmias?", "id": "converted_19", "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, indication with Everolimus, indication with Everolimus, 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. Definitions: 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.. 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.. 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.. 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.. 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: This gene is involved in the maintenance of connective tissue.. Cardiac complications defined as following: Any heart or vascular disorder occurring as a consequence of injury to the cardiovascular system.. 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.. 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..", "label": "yes"}
{"original_question": "Is there a relationship between junctin and ryanodine receptors?", "id": "converted_20", "sentence1": "Is there a relationship between junctin and ryanodine receptors?", "sentence2": "Junctin, a 26 kDa intra-sarcoplasmic reticulum (SR) protein, forms a quaternary complex with triadin, calsequestrin and the ryanodine receptor (RyR) at the junctional SR membrane.  Junctin ablation appears to affect how RyRs 'sense' SR Ca(2+) load, resulting in decreased diastolic SR Ca(2+) leak despite an elevated [Ca(2+)](SR).  Single channel recordings of RyRs from WT and JCN-KO cardiac SR indicate that the absence of junctin produces a dual effect on the normally linear response of RyRs to luminal [Ca(2+)]: at low luminal [Ca(2+)] (<1 mmol l(-1)), junctin-devoid RyR channels are less responsive to luminal [Ca(2+)]; conversely, high luminal [Ca(2+)] turns them hypersensitive to this form of channel modulation. Thus, junctin produces complex effects on Ca(2+) sparks, transients, and leak, but the luminal [Ca(2+)]-dependent dual response of junctin-devoid RyRs demonstrates that junctin normally acts as an activator of RyR channels at low luminal [Ca(2+)], and as an inhibitor at high luminal [Ca(2+)]. Normal Ca(2+) signalling in skeletal muscle depends on the membrane associated proteins triadin and junctin and their ability to mediate functional interactions between the Ca(2+) binding protein calsequestrin and the type 1 ryanodine receptor in the lumen of the sarcoplasmic reticulum. We show here that purified skeletal ryanodine receptors are similarly activated by purified triadin or purified junctin added to their luminal side, although a lack of competition indicated that the proteins act at independent sites. Surprisingly, triadin and junctin differed markedly in their ability to transmit information between skeletal calsequestrin and ryanodine receptors. Purified calsequestrin inhibited junctin/triadin-associated, or junctin-associated, ryanodine receptors and the calsequestrin re-associated channel complexes were further inhibited when luminal Ca(2+) fell from 1mM to By fusing GCaMP6f to the N-terminus of triadin 1 or junctin, GCaMP6f-T/J was targeted to dyadic junctions, where it colocalized with t-tubules and RyRs after adenovirus-mediated gene transfer.  The junctional face of the jSR, facing the transverse tubules, is occupied by a molecular complex composed of the transmembrane Ca2+ release channels (ryanodine receptors); the luminal protein calsequestrin (CSQ); the 2 membrane proteins, junctin (Jct), and triadin (Tr), which mediate CSQ-ryanodine receptor interactions; and several other components. Calsequestrin, the main calcium buffer in the sarcoplasmic reticulum, provides a pool of calcium for release through the ryanodine receptor and acts as a luminal calcium sensor for the channel via its interactions with triadin and junctin. We examined the influence of phosphorylation of calsequestrin on its ability to store calcium, to polymerise and to regulate ryanodine receptors by binding to triadin and junctin.  Junctin is a 26 kDa membrane protein that binds to calsequestrin, triadin, and ryanodine receptors (RyRs) within the junctional sarcoplasmic reticulum of calcium release units.[SEP]Relations: ryanodine receptor complex has relations: cellcomp_protein with RYR1, cellcomp_protein with RYR1, cellcomp_protein with RYR1, cellcomp_protein with RYR1, cellcomp_protein with RYR1, cellcomp_protein with RYR1, cellcomp_cellcomp with voltage-gated calcium channel complex, cellcomp_cellcomp with voltage-gated calcium channel complex, cellcomp_cellcomp with voltage-gated calcium channel complex, cellcomp_cellcomp with voltage-gated calcium channel complex. Definitions: 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.. 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]. calcium defined as following: A dietary supplement containing the mineral calcium.. 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.. junctin defined as following: This gene is involved in calcium ion channel regulation and amino acid hydroxylation.. Junctin defined as following: This gene is involved in calcium ion channel regulation and amino acid hydroxylation.. 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.. 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.. membrane defined as following: A device that is made from or resembles a thin flexible sheet of material.. 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.. luminal defined as following: Relating to the lumen of a blood vessel or other tubular structure.. WT defined as following: A designation used to describe a wild-type zebrafish line that is of unknown stock.. type 1 ryanodine receptor defined as following: Ryanodine receptor 1 (5038 aa, ~565 kDa) is encoded by the human RYR1 gene. This protein is involved in the transport of calcium ions from the sarcoplasmic reticulum and neurons..", "label": "yes"}
{"original_question": "Is JTV519 (K201) a potential drug for the prevention of arrhythmias?", "id": "converted_21", "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: phenotype_protein with KCNJ8, phenotype_protein with KCNJ8, phenotype_protein with KCNJ2, phenotype_protein with KCNJ2, drug_effect with Oseltamivir, drug_effect with Oseltamivir, drug_effect with Venlafaxine, drug_effect with Venlafaxine. Dantrolene has relations: drug_drug with JNJ-26489112, drug_drug with JNJ-26489112. Definitions: 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]. 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 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.. diltiazem defined as following: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of CALCIUM ion on membrane functions.. 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). 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.. 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.. polymorphic defined as following: The quality or state of being able to assume different forms.. 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.. 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.. 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. 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.. ventricular arrhythmia defined as following: 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.. 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).. 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..", "label": "yes"}
{"original_question": "Is Propofol used for short-term sedation?", "id": "converted_22", "sentence1": "Is Propofol used for short-term sedation?", "sentence2": "The current study explores the incidence and content of dreaming during short-term sedation with sevoflurane or propofo Propofol is the sedative most frequently used for short-term sedation and the weaning phase, whereas benzodiazepines are the preferred substances for medium- and long-term sedation. Performance of the A-line Autoregressive Index (AAI) and of the Bispectral Index (BIS) at assessing depth of short-term sedation following cardiac surgery. All patients received sedation with propofol according to the study protocol. Short-term sedation with either sevoflurane using ACD or propofol did not negatively affect renal function postoperatively. Assessing feasibility and physiological effects of sedation with sevoflurane, administered with the anesthetic conserving device (AnaConDa), in comparison with propofol and remifentanil. Sevoflurane can be effectively and safely used for short-term sedation of ICU patients with stable hemodynamic conditions. Propofol was used for most of the patients during short-term sedation (57%) and during weaning (48%). Effects of short-term propofol administration on pancreatic enzymes and triglyceride levels in children. This prospective, clinical trial evaluated the effects of short-term propofol administration on triglyceride levels and serum pancreatic enzymes in children undergoing sedation for magnetic resonance imaging. Dexmedetomidine vs. propofol for short-term sedation of postoperative mechanically ventilated patients. The aim of this study was to compare the efficacy and endocrine response of propofol vs. the new alpha2-agonist dexmedetomidine for sedation in surgical intensive care patients who need postoperative short-term ventilation. A total of 89 adult, nonemergent, coronary artery bypass graft patients with an expected length of intubation of <24 hrs. METHODS: Patients were randomized to either DEX or propofol The majority of practitioners (82%) use propofol infusion in children in PICU, the main indication being for short-term sedation in children requiring procedures. Pharmacokinetics and effects of propofol 6% for short-term sedation in paediatric patients following cardiac surgery. This paper describes the pharmacokinetics and effects of propofol in short-term sedated paediatric patients. Twenty patients who were expected to require 8 h of post-operative sedation and ventilation were allocated randomly to receive either an infusion of dexmedetomidine 0.2-2.5 microg kg(-1) h(-1) or propofol 1-3 mg kg(-1) h(-1) Pharmacokinetics and pharmacodynamics of propofol 6% SAZN versus propofol 1% SAZN and Diprivan-10 for short-term sedation following coronary artery bypass surgery. The pharmacokinetics, pharmacodynamics and safety characteristics of propofol 6% SAZN were investigated during a short-term infusion and compared with the commercially available product propofol 1% in Intralipid 10% (Diprivan-10) and propofol 1% in Lipofundin MCT/LCT 10% (propofol 1% SAZN). METHODS: In a randomised double-blind study, 24 male patients received a 5-h infusion of propofol at the rate of 1 mg/kg/h for sedation in the immediate postoperative period following coronary artery bypass surgery Propofol infusion and oxycodone-thiopental bolus dosages, titrated to the same sedation end point, resulted in similar time from admission to extubation, although the weaning period was shorter in the propofol group. In terms of breathing pattern, gas exchange, blood gases and haemodynamics, the methods were similar. Propofol, despite its attractive pharmacological profile, may offer no clinical benefit in short-term sedation after a moderate dose fentanyl anaesthesia in cardiac surgery. Postoperative short-term sedation with propofol in cardiac surgery. We conducted a randomized double-blind study to assess the safety and effectiveness of short-term sedation with propofol in adult patients immediately after cardiac surgery. The use of propofol for short-term sedation in ICUs has allowed the maintenance of sedation to continue until just a few hours before extubation but the benefits of propofol for longer-term indications are more debatable. Midazolam and propofol are available as hypnotics for short-term sedation during the post-operative period. The use of midazolam versus propofol for short-term sedation following coronary artery bypass grafting. Midazolam and propofol were compared in an open randomized study for postoperative sedation during 12 h of mechanical ventilation in 40 patients following coronary artery bypass grafting Propofol is a known anesthetic agent, widely used for short-term anesthesia and for longer-term sedation. Propofol was the most commonly used agent overall during the observational period (primarily for short-term and intermediate-length sedation); midazolam was the most commonly used for long-term sedation.[SEP]Relations: Propofol has relations: drug_drug with Selegiline, drug_drug with Selegiline, contraindication with epilepsy, contraindication with epilepsy, drug_drug with Propacetamol, drug_drug with Propacetamol, drug_drug with Propanidid, drug_drug with Propanidid, drug_drug with Diamorphine, drug_drug with Diamorphine. Definitions: 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.. remifentanil defined as following: A piperidine-propionate derivative and opioid analgesic structurally related to FENTANYL. It functions as a short-acting MU OPIOID RECEPTOR agonist, and is used as an analgesic during induction or maintenance of general anesthesia, following surgery, during childbirth, and in mechanically ventilated patients under intensive care.. 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.. 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.. 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.. benzodiazepines defined as following: A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.. pancreatic enzymes defined as following: Pancreatic enzymes are comprised primarily of proteases, lipase and amylase that catalyze the breakdown of fats, carbohydrates and proteins during the digestion of food. However, the pancreas also produces many other digestive enzymes such as ribonuclease, deoxyribonuclease, gelatinase and elastase.. substances defined as following: Any matter of defined composition that has discrete existence, whose origin may be biological, mineral or chemical.. 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..", "label": "yes"}
{"original_question": "Is cocaine use associated with increased risk for intracerebral hemorrhage?", "id": "converted_23", "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.. 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.. hypercholesterolemia defined as following: A laboratory test result indicating an increased amount of cholesterol in the blood.. hemorrhagic strokes defined as following: An acute episode of focal or global cerebral or spinal dysfunction caused by intraparenchymal, intraventricular, or subarachnoid hemorrhage.. ischemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue.. SAH defined as following: A Turkic language spoken by the Yakut people in the Sakha Republic in the Russian Federation.. 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.. intracranial hemorrhage defined as following: Bleeding within the cranium.. 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.. rupture defined as following: Forcible or traumatic tear or break of an organ or other soft part of the body.. 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.. 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). 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.. diabetes defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.. 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.. 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.. 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.. hemorrhages defined as following: Bleeding or escape of blood from a vessel.. intracerebral defined as following: Administration of a drug within the cerebrum, directly into brain tissue, usually by injection or direct application.. 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.. 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.. neurologic deficits defined as following: Loss of movement function.. 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"}
{"original_question": "Is COL5A2 gene associated to ischemic heart disease?", "id": "converted_24", "sentence1": "Is COL5A2 gene associated to ischemic heart disease?", "sentence2": "Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease Col5a2, a gene previously not specifically linked to MI response but responsible for the classic type of Ehlers-Danlos syndrome, was found to have many and strong co-expression associations within this community Col5a2 shows predictive potential in MI, and in principle may represent a novel candidate marker for the identification and treatment of ischemic cardiovascular disease Analysis of a gene co-expression network establishes robust association between Col5a2 and ischemic heart disease.[SEP]Relations: myocardial ischemia has relations: disease_protein with ADM2, disease_protein with ADM2, disease_protein with ADRB2, disease_protein with ADRB2, disease_protein with TMED2, disease_protein with TMED2, disease_protein with RAB5A, disease_protein with RAB5A, disease_protein with APLP2, disease_protein with APLP2. Definitions: Col5a2 defined as following: Collagen alpha-2(V) chain (1499 aa, ~145 kDa) is encoded by the human COL5A2 gene. This protein is involved in collagen fibril formation in connective tissues.. 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.. 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).. 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.. COL5A2 gene defined as following: This gene is involved in connective tissue development and extracellular matrix formation..", "label": "yes"}
{"original_question": "Are there Conserved Noncoding Elements (CNEs) in invertebrate genomes?", "id": "converted_25", "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.. 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.. 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).. 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.. 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..", "label": "yes"}
{"original_question": "Is HER2 active only when it dimerizes?", "id": "converted_26", "sentence1": "Is HER2 active only when it dimerizes?", "sentence2": "HER activation is driven by the formation of various dimer complexes between members of this receptor family. rtuzumab is the first humanized monoclonal antibody in a new class of drugs, the HER dimerization inhibitors, approved by the Food and Drug Pertuzumab is a novel anti-HER2 monoclonal antibody, which blocks HER2 dimerization with other ligand-activated HER family members. Here, we explored the complement-mediated anti-tumor effects of trastuzumab and pertuzumab on HER2-positive tumor cells of various histological origins. ays. In this study, we report that an anti-HER2 monoclonal antibody (HER2Mab), which blocks HER2 dimerization with HER3, induces HER3 dimerization with EGFR in both low and high HER2 expressing cancer cells. Recent evidence from both basic and clinical studies suggests that ERBB3 (HER3) serves as a key activator of downstream signaling through dimerization with other ERBB proteins and plays a critical role in the widespread clinical resistance to EGFR and HER2 targeting cancer therapies.  HER3 intracellular domains play a crucial role in HER3/HER2 dimerization and activation of downstream signaling pathways. Dimerization among the EGFR family of tyrosine kinase receptors leads to allosteric activation of the kinase domains of the partners. Our results show that quantification of HER dimerization provides information about receptor activation that cannot be obtained by quantification of single receptors.  Pertuzumab is a novel humanized monoclonal antibody that blocks human epidermal growth factor receptor 2 (HER2) dimerization. It was recently approved by the US FDA for use in combination with trastuzumab and docetaxel for patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.  he HER dimerization status may be more important than HER receptor expression per se in determining sensitivity or resistance to a given therapeutic agen  and HER2 dimerization inhibitors One of the mechanisms by which tumor cell proliferation can be inhibited consists in hampering HER2 dimerization by targeting its extracellular domain with specific antibodies.  Pertuzumab, a humanized monoclonal antibody, is the first HER2 dimerization inhibitor. It binds to the dimerization site on the HER2 domain and prevents ligand-driven pairing of HER2 with other HER receptors, thus inhibiting tumor cell growth and survival Pertuzumab, another monoclonal antibody, is a HER2 dimerization inhibitor that binds to a different epitope on HER2 than trastuzumab and inhibits HER2 dimer formation with other HER family members such as HER3 and HER1.[SEP]Relations: Trastuzumab has relations: indication with HER2 positive breast carcinoma, indication with HER2 positive breast carcinoma. ERBB3 has relations: protein_protein with ACTR2, protein_protein with ACTR2, molfunc_protein with protein heterodimerization activity, molfunc_protein with protein heterodimerization activity, molfunc_protein with protein tyrosine kinase activator activity, molfunc_protein with protein tyrosine kinase activator activity. Pertuzumab has relations: indication with HER2 positive breast carcinoma, indication with HER2 positive breast carcinoma. Definitions: HER1 defined as following: This gene is involved in the epidermal growth factor signal transduction pathway.. pertuzumab defined as following: A humanized recombinant monoclonal antibody directed against the extracellular dimerization domain of the HER-2 tyrosine kinase receptor. Binding of the antibody to the dimerization domain of the HER-2 tyrosine kinase receptor protein directly inhibits the ability of the HER-2 tyrosine kinase receptor protein (the most common pairing partner) to dimerize with other HER tyrosine kinase receptor proteins; inhibiting receptor protein dimerization prevents the activation of HER signaling pathways, resulting in tumor cell apoptosis. (NCI04). extracellular domain defined as following: Any part of a transmembrane protein that projects into the environment surrounding a cell.. HER defined as following: A Niger-Congo Bantu language spoken by the Herero and Mbanderu peoples in Namibia and Botswana.. 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.. 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.. 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.. 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). epitope defined as following: Sites on an antigen that interact with specific antibodies.. 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.. tyrosine kinase receptors defined as following: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.. ERBB3 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.. HER3 defined as following: A cell surface protein-tyrosine kinase receptor that is specific for NEUREGULINS. It has extensive homology to and can heterodimerize with the EGF RECEPTOR and the ERBB-2 RECEPTOR. Overexpression of the erbB-3 receptor is associated with TUMORIGENESIS.. cancer cells defined as following: Cells of, or derived from, a malignant tumor.. EGFR family defined as following: A family of structurally related cell-surface receptors that signal through an intrinsic PROTEIN-TYROSINE KINASE. The receptors are activated upon binding of specific ligands which include EPIDERMAL GROWTH FACTORS, and NEUREGULINS.. tumor cell defined as following: Cells of, or derived from, a tumor..", "label": "yes"}
{"original_question": "Is Crohn's disease (CD) linked to the consumption of refrigerated food?", "id": "converted_27", "sentence1": "Is Crohn's disease (CD) linked to the consumption of refrigerated food?", "sentence2": "Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01-4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. A recent published hypothesis proposed that Crohn's disease was provoked by infantile exposure to micro-organisms that can survive refrigerator temperature. This support for the hypothesis reached statistical significance for those with Crohn's disease compared to the controls (p=0.045). Epidemiological data allow assessment of familial environmental risk factors related to western lifestyle, diet, bacteria, and domestic hygiene. All findings point to refrigeration as a potential risk factor for Crohn's disease. Furthermore, cold-chain development paralleled the outbreak of Crohn's disease during the 20th century.  Environmental risk factors playing a causative role in Crohn&apos;s Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. Our study suggests an association between the omission of breakfast and the failure to refrigerate food with GC in the Mexican population.[SEP]Relations: Crohn disease of the esophagus has relations: disease_disease with Crohn disease, disease_disease with Crohn disease, disease_disease with esophagitis (disease), disease_disease with esophagitis (disease). Bacteremia has relations: disease_phenotype_positive with toxic shock syndrome, disease_phenotype_positive with toxic shock syndrome, disease_phenotype_positive with listeriosis, disease_phenotype_positive with listeriosis, disease_phenotype_positive with cyclic hematopoiesis, disease_phenotype_positive with cyclic hematopoiesis. Definitions: micro-organisms defined as following: A microscopic organism. The term microorganism may refer to a prokaryote or eukaryote, and may be a unicellular or multicellular organism. All taxonomic kingdoms contain microorganisms.. 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.. Crohn's 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..", "label": "yes"}
{"original_question": "Is the UGT1A1*28 polymorphism associated with irinotecan response in Caucasians?", "id": "converted_28", "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: 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.. variants defined as following: An alteration or difference from a norm or standard.. 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.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. 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.. 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"}
{"original_question": "Can clonidine be used to reduce agitation in children.", "id": "converted_29", "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 \u03bcg kg\u207b\u00b9). 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 \u03bcg kg\u207b\u00b9) 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: 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.. 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.. 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.. 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.. 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.. 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.. sleepiness defined as following: Compelling urge to sleep.. 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.. 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.. 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.. 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..", "label": "yes"}
{"original_question": "Is there an association between presenteeism and depression?", "id": "converted_30", "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\u2009=\u2009-3.29, p\u2009=\u20090.001). 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: presenteeism defined as following: Reporting for work despite feeling ill.. arthritis defined as following: Acute or chronic inflammation of JOINTS.. 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.. depressed defined as following: An emotional state characterized by feelings of sadness, emptiness, and/or tearfulness.. illness defined as following: A state of ill health, bodily malfunction, or discomfort.. mood disorders defined as following: Those disorders that have a disturbance in mood as their predominant feature.. musculoskeletal pain defined as following: Discomfort stemming from muscles, LIGAMENTS, tendons, and bones.. 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). 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.. anxiety defined as following: Persistent and disabling ANXIETY..", "label": "yes"}
{"original_question": "Are OATP1B1 and OATP1B3 associated with bilirubin transport?", "id": "converted_31", "sentence1": "Are OATP1B1 and OATP1B3 associated with bilirubin transport?", "sentence2": "OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir.  Examples of adaptive nontoxic changes in liver function, which may elevate direct (conjugated) and/or indirect (unconjugated) bilirubin above baseline levels, include reversible inhibition of UGT1A1-mediated bilirubin metabolism and OATP1B1-, OATP1B3-, or MRP2-mediated transport (Keogh. Due to limited solubility and poor ionization of bilirubin and its glucuronide, the formation of estradiol 3-glucuronide was used as a surrogate to assess UGT1A1 activity, while the transport of pitavastatin, CDCF, and taurocholate were used as surrogate probe substrates to monitor the function of OATP1B1/OATP1B3, MRP2, and BSEP, respectively. OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir. However, because drug transporters also contribute to bilirubin elimination, the purpose of this work was to investigate the in vitro inhibition of OATP1B1, OATP1B3, MRP2, and BSEP of select test drugs known to elicit hyperbilirubinemia. Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia.Moreover, OATP1B1 and OATP1B3 null mutations may confer substantial drug toxicity risks. Bilirubin elimination is a multifaceted process consisting of uptake of bilirubin into the hepatocytes facilitated by OATP1B1 and OATP1B3. Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia. The data show that a substantial fraction of bilirubin conjugates is primarily secreted by MRP3 at the sinusoidal membrane into the blood, from where they are subsequently reuptaken by sinusoidal membrane-bound organic anion transporting polypeptides OATP1B1 and OATP1B3. Evaluating the in vitro inhibition of UGT1A1, OATP1B1, OATP1B3, MRP2, and BSEP in predicting drug-induced hyperbilirubinemia. OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir Bilirubin elimination is a multifaceted process consisting of uptake of bilirubin into the hepatocytes facilitated by OATP1B1 and OATP1B3 Due to limited solubility and poor ionization of bilirubin and its glucuronide, the formation of estradiol 3-glucuronide was used as a surrogate to assess UGT1A1 activity, while the transport of pitavastatin, CDCF, and taurocholate were used as surrogate probe substrates to monitor the function of OATP1B1/OATP1B3, MRP2, and BSEP, respectively Examples of adaptive nontoxic changes in liver function, which may elevate direct (conjugated) and/or indirect (unconjugated) bilirubin above baseline levels, include reversible inhibition of UGT1A1-mediated bilirubin metabolism and OATP1B1-, OATP1B3-, or MRP2-mediated transport (Keogh In vitro, faldaprevir inhibited key processes involved in bilirubin clearance: UDP glucuronosyltransferase (UGT) 1A1 (UGT1A1) (IC50 0.45 \u00b5M), which conjugates bilirubin, and hepatic uptake and efflux transporters, organic anion-transporting polypeptide (OATP) 1B1 (IC50 0.57 \u00b5M), OATP1B3 (IC50 0.18 \u00b5M), and multidrug resistance-associated protein (MRP) 2 (IC50 6.2 \u00b5M), which transport bilirubin and its conjugates Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia Thus, disruption of hepatic reuptake of bilirubin glucuronide due to coexisting OATP1B1 and OATP1B3 deficiencies explains Rotor-type hyperbilirubinemia.Moreover, OATP1B1 and OATP1B3 null mutations may confer substantial drug toxicity risks OATP1B1 (a.k.a. OATP-C, OATP2, LST-1, or SLC21A6) is a liver-specific organic anion uptake transporter and has been shown to be a higher affinity bilirubin uptake transporter than OATP1B3 In vitro OATP1B1 and OATP1B3 inhibition is associated with observations of benign clinical unconjugated hyperbilirubinemia. Examples of adaptive nontoxic changes in liver function, which may elevate direct (conjugated) and/or indirect (unconjugated) bilirubin above baseline levels, include reversible inhibition of UGT1A1-mediated bilirubin metabolism and OATP1B1-, OATP1B3-, or MRP2-mediated transport (Keogh. Adv Pharmacol 63:1-42, 2012).  Using mice deficient in Oatp1a/1b and in the multispecific sinusoidal export pump Abcc3, we found that Abcc3 secretes bilirubin conjugates into the blood, while Oatp1a/1b transporters mediate their hepatic reuptake.  Bilirubin elimination is a multifaceted process consisting of uptake of bilirubin into the hepatocytes facilitated by OATP1B1 and OATP1B3.  OATP1B1 polymorphism is a major determinant of serum bilirubin level but not associated with rifampicin-mediated bilirubin elevation. Unconjugated bilirubin (UCB) is taken up into hepatocytes by human organic anion transporting polypeptide 1B1 (OATP1B1; encoded for by the SLCO1B1 gene). However, because drug transporters also contribute to bilirubin elimination, the purpose of this work was to investigate the in vitro inhibition of OATP1B1, OATP1B3, MRP2, and BSEP of select test drugs known to elicit hyperbilirubinemia. Test drugs investigated in this study were atazanavir and indinavir, which are associated with hyperbilirubinemia and elevations in serum transaminase; ritonavir and nelfinavir, which are not associated with hyperbilirubinemia; and bromfenac, troglitazone, and trovafloxacin, which are associated with severe idiosyncratic hepatotoxicity exhibiting elevations in serum bilirubin and transaminase. Test drugs investigated in this study were atazanavir and indinavir, which are associated with hyperbilirubinemia and elevations in serum transaminase; ritonavir and nelfinavir, which are not associated with hyperbilirubinemia; and bromfenac, troglitazone, and trovafloxacin, which are associated with severe idiosyncratic hepatotoxicity exhibiting elevations in serum bilirubin and transaminase. Due to limited solubility and poor ionization of bilirubin and its glucuronide, the formation of estradiol 3-glucuronide was used as a surrogate to assess UGT1A1 activity, while the transport of pitavastatin, CDCF, and taurocholate were used as surrogate probe substrates to monitor the function of OATP1B1/OATP1B3, MRP2, and BSEP, respectively. In vitro, faldaprevir inhibited key processes involved in bilirubin clearance: UDP glucuronosyltransferase (UGT) 1A1 (UGT1A1) (IC50 0.45 \u00b5M), which conjugates bilirubin, and hepatic uptake and efflux transporters, organic anion-transporting polypeptide (OATP) 1B1 (IC50 0.57 \u00b5M), OATP1B3 (IC50 0.18 \u00b5M), and multidrug resistance-associated protein (MRP) 2 (IC50 6.2 \u00b5M), which transport bilirubin and its conjugates. In vitro OATP1B1 and OATP1B3 inhibition is associated with observations of benign clinical unconjugated hyperbilirubinemia. 3.\u2002\u2009The results indicated that in vivo Fi values >0.2 or R-values >1.5 for OATP1B1 or OATP1B3, but not UGT1A1, are associated with previously reported clinical cases of drug-induced unconjugated hyperbilirubinemia. OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir.[SEP]Relations: UGT1A1 has relations: disease_protein with bilirubin encephalopathy, disease_protein with bilirubin encephalopathy, bioprocess_protein with bilirubin conjugation, bioprocess_protein with bilirubin conjugation, protein_protein with B3GALT1, protein_protein with B3GALT1, drug_protein with Alvocidib, drug_protein with Alvocidib. SLCO1B1 has relations: molfunc_protein with bile acid transmembrane transporter activity, molfunc_protein with bile acid transmembrane transporter activity. Definitions: glucuronide defined as following: Glycosides of GLUCURONIC ACID formed by the reaction of URIDINE DIPHOSPHATE GLUCURONIC ACID with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and BILIRUBIN metabolism to a more water-soluble compound that can be eliminated in the URINE and BILE.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. Abcc3 defined as following: Canalicular multispecific organic anion transporter 2 (1527 aa, ~169 kDa) is encoded by the human ABCC3 gene. This protein is involved in both the transport and metabolism of bile.. atazanavir defined as following: An aza-dipeptide analogue with a bis-aryl substituent on the (hydroxethyl)hydrazine moiety with activity against both wild type and mutant forms of HIV protease. Atazanavir does not elevate serum lipids, a common problem with other protease inhibitors.. bilirubin defined as following: A bile pigment that is a degradation product of HEME.. SLCO1B1 gene defined as following: This gene is involved in sodium-independent uptake of numerous endogenous compounds in the liver.. BSEP defined as following: Human ABCB11 wild-type allele is located in the vicinity of 2q24 and is approximately 108 kb in length. This allele, which encodes bile salt export pump protein, is involved in bile salt transport. Mutation of the gene is associated with hereditary intrahepatic cholestasis.. OATP2 defined as following: Human SLCO1B1 wild-type allele is located in the vicinity of 12p12 and is approximately 109 kb in length. This allele, which encodes solute carrier organic anion transporter family member 1B1 protein, plays a role in both endogenous factor uptake in the liver and the removal of drug compounds. Mutations in this gene are associated with hyperbilirubinemia, Rotor type, digenic.. OATP1B3 defined as following: Human SLCO1B3 wild-type allele is located in the vicinity of 12p12 and is approximately 279 kb in length. This allele, which encodes solute carrier organic anion transporter family member 1B3 protein, is involved in both bile acid and bilirubin transport and sodium-independent uptake of endogenous and xenobiotic compounds. Mutations in this gene are associated with hyperbilirubinemia, Rotor type, digenic.. nelfinavir defined as following: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children.. MRP3 defined as following: Human ABCC3 wild-type allele is located in the vicinity of 17q22 and is approximately 57 kb in length. This allele, which encodes canalicular multispecific organic anion transporter 2 protein, plays a role in bile metabolism and transport.. human defined as following: Members of the species Homo sapiens.. indinavir defined as following: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability.. hepatocytes defined as following: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.. amprenavir defined as following: A synthetic derivative of hydroxyethylamine sulfonamide that selectively binds to and inhibits human immunodeficiency virus (HIV) protease.. troglitazone defined as following: A chroman and thiazolidinedione derivative that acts as a PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPAR) agonist. It was formerly used in the treatment of TYPE 2 DIABETES MELLITUS, but has been withdrawn due to hepatotoxicity.. rifampicin defined as following: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160). saquinavir defined as following: An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases, and also inhibits CYTOCHROME P-450 CYP3A.. pitavastatin defined as following: A novel statin that induces plaque regression and elevates HDL-cholesterol levels.. MRP defined as following: A sequence-related subfamily of ATP-BINDING CASSETTE TRANSPORTERS that actively transport organic substrates. Although considered organic anion transporters, a subset of proteins in this family have also been shown to convey drug resistance to neutral organic drugs. Their cellular function may have clinical significance for CHEMOTHERAPY in that they transport a variety of ANTINEOPLASTIC AGENTS. Overexpression of proteins in this class by NEOPLASMS is considered a possible mechanism in the development of multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although similar in function to P-GLYCOPROTEINS, the proteins in this class share little sequence homology to the ATP BINDING CASSETTE TRANSPORTER, SUBFAMILY B, MEMBER 1 family of proteins.. cyclosporine 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).. hyperbilirubinemia defined as following: A benign, autosomally recessive inherited hyperbilirubinemia characterized by the presence of a dark pigment in the centrilobular region of the liver cells. There is a functional defect in biliary excretion of bilirubin, cholephilic dyes, and porphyrins. Affected persons may be asymptomatic or have vague constitutional or gastrointestinal symptoms. The liver may be slightly enlarged, and oral and intravenous cholangiography fails to visualize the biliary tract.. UGT1A1 defined as following: This gene is involved in controlling serum levels of bilirubin and in glucuronidation.. 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.. MRP2 defined as following: Human ABCC2 wild-type allele is located in the vicinity of 10q24 and is approximately 69 kb in length. This allele, which encodes canalicular multispecific organic anion transporter 1 protein, plays a role in both multidrug resistance and organic anion transport. Mutation of the gene is associated with Dubin-Johnson syndrome.. bilirubin glucuronide defined as following: water soluble conjugated bilirubin.. bromfenac defined as following: A nonsteroidal anti-inflammatory drug (NSAID) with analgesic and anti-inflammatory activities. Upon ophthalmic administration, bromfenac binds to and inhibits the activity of cyclooxygenase II (COX II), an enzyme which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins (PG). By inhibiting PG formation, bromfenac is able to inhibit PG-induced inflammation, thereby preventing vasodilation, leukocytosis, disruption of the blood-aqueous humor barrier, an increase in vascular permeability and an increase in intraocular pressure (IOP).. rifamycin SV defined as following: A natural antibiotic produced by Streptomyces mediterranei, Rifamycin (Ansamycin Family) is a commonly used antimycobacterial drug that inhibits prokaryotic DNA-dependent RNA synthesis and protein synthesis; it blocks RNA-polymerase transcription initiation. Rifamycin has an activity spectrum against Gram-positive and Gram-negative bacteria, but is mainly used against Mycobacterium sp. (especially M. tuberculosis) in association with other agents to overcome resistance. (NCI04). transaminase 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.. ritonavir defined as following: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A.. conjugates defined as following: A compound formed by the union of two entities or compounds.. probe defined as following: brand name of methazole herbicide. UDP glucuronosyltransferase defined as following: A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17.. OATP1B1 defined as following: Human SLCO1B1 wild-type allele is located in the vicinity of 12p12 and is approximately 109 kb in length. This allele, which encodes solute carrier organic anion transporter family member 1B1 protein, plays a role in both endogenous factor uptake in the liver and the removal of drug compounds. Mutations in this gene are associated with hyperbilirubinemia, Rotor type, digenic..", "label": "yes"}
{"original_question": "Is abdominal pain a common symptom in autism?", "id": "converted_32", "sentence1": "Is abdominal pain a common symptom in autism?", "sentence2": "Participants included 132 children with ASD and 81 with special educational needs (SEN) but no ASD, aged 10-14\u00a0years plus 82 typically developing (TD) children The ASD group had significantly increased past vomiting and diarrhoea compared with the TD group and more abdominal pain than the SEN group Many children with autism spectrum disorders (ASDs) suffer from gastrointestinal problems such as diarrhoea, constipation and abdominal pain Children with autism spectrum disorders (ASD) experience high rates of anxiety, sensory processing problems, and gastrointestinal (GI) problems The results indicate that anxiety, sensory over-responsivity and GI problems are possibly interrelated phenomenon for children with ASD, and may have common underlying mechanisms. Lactase deficiency not associated with intestinal inflammation or injury is common in autistic children and may contribute to abdominal discomfort, pain and observed aberrant behavior. Autistic behavior is often accompanied by numerous disturbing symptoms on the part of gastrointestinal system, such as abdominal pain, constipation or diarrhea. Information on children's stool patterns and gut symptoms collected by questionnaire at 4 weeks and at 6, 18, 30 and 42 months of age were available for 12,984 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) Comparison of the ASD and control group during the first 3.5 years of life showed no major differences in stool colour or consistency, or in frequency of diarrhoea, constipation, bloody stools or abdominal pain. Constipation is a frequent finding in children with gastrointestinal symptoms and autism, particularly in the rectosigmoid colon, often with acquired megarectum. The absence of any correlation between the clinical history and the degree of fecal impaction in autistic children confirms the importance of an abdominal radiograph in the assessment of their degree of constipation. In a sample of 137 children, age 24-96 months, classified as having autism or ASD by the Autism Diagnostic Observation Schedule-Generic, 24 percent had a history of at least one chronic gastrointestinal symptom. The most common symptom was diarrhea, which occurred in 17 percent.[SEP]Relations: Abdominal pain has relations: phenotype_phenotype with Abdominal symptom, phenotype_phenotype with Abdominal symptom, phenotype_phenotype with Pain, phenotype_phenotype with Pain, phenotype_phenotype with Episodic abdominal pain, phenotype_phenotype with Episodic abdominal pain, disease_phenotype_positive with plague, disease_phenotype_positive with plague, disease_phenotype_positive with congenital diarrhea, disease_phenotype_positive with congenital diarrhea. Definitions: 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.. Lactase deficiency defined as following: Lactase is produced in the small intestine in humans, Lactase is a member of the beta-galactosidase family of enzymes, and hydrolyzes D-lactose to form D-galactose and D-glucose, which can be absorbed by the small intestine. There are many ways of assessing lactase activity. In one test, an endoscopic biopsy from the postbulbar duodenum is incubated with lactose on a test plate, and a color reaction develops within 20 min as a result of hydrolyzed lactose (a positive result) in patients with normolactasia, whereas no reaction (a negative result) develops in patients with severe hypolactasia. Other, less direct, tests include the hydrogen breath test, and blood tests following lactose challenges. []. 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). TD defined as following: <p><a href=\"https://medlineplus.gov/tetanus.html\">Tetanus</a>, <a href=\"https://medlineplus.gov/diphtheria.html\">diphtheria</a>, and <a href=\"https://medlineplus.gov/whoopingcough.html\">pertussis</a> (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:</p> <ul> <li>DTaP prevents all three diseases. It is for children younger than seven years old.</li> <li>Tdap also prevents all three. It is for older children and adults.</li> <li>DT prevents diphtheria and tetanus. It is for children younger than seven who cannot tolerate the pertussis vaccine.</li> <li>Td prevents diphtheria and tetanus. It is for older children and adults. It is usually given as a booster dose every 10 years. You may also get it earlier if you get a severe and dirty wound or burn.</li> </ul> <p>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 <a href=\"https://medlineplus.gov/guillainbarresyndrome.html\">Guillain-Barre syndrome</a>. Also let your doctor know if you don't feel well the day of the shot; you may need to postpone it.</p> <p class=\"\">Centers for Disease Control and Prevention</p>. 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]. rectosigmoid colon defined as following: A portion of the large intestine that includes the descending colon, sigmoid colon and rectum.. diarrhoea 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.. 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.. anxiety defined as following: Persistent and disabling ANXIETY.. 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.. 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.. abdominal pain defined as following: Sensation of discomfort, distress, or agony in the abdominal region.. 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].", "label": "yes"}
{"original_question": "Are cyclophilins ubiquitously expressed?", "id": "converted_33", "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: immunophilin defined as following: An enzyme that catalyzes the isomerization of proline residues within proteins. EC 5.2.1.8.. 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.. 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.. FK506-binding proteins defined as following: A family of immunophilin proteins that bind to the immunosuppressive drugs TACROLIMUS (also known as FK506) and SIROLIMUS.. organisms defined as following: A living entity.. 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).. 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.. 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.. 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"}
{"original_question": "Does low T3 negatively affect prognosis of patients after cardiac surgery?", "id": "converted_34", "sentence1": "Does low T3 negatively affect prognosis of patients after cardiac surgery?", "sentence2": "ur findings suggest that the development of LCOS after congenital heart surgery is associated with decreased total and free T3, and increased IL-8 levels at 48 hours, and preoperative tT4 level is an independent predictor of LCOS. Low basal fT3 concentration can reliably predict the occurrence of postoperative AF in CABG patients. A relevant finding was that the days of post-operative hospitalization (10+/-3 days, means+/-S.D.) was inversely correlated with the slope of the recovery of T3 concentration (P<0.001) or with the area under the plasma curves of T3 (P=0.024, time range 72-144 h) and the FT3/FT4 ratio (P=0.037, time range 72-144 h) during the post-operative period.[SEP]Relations: interleukin-8 receptor activity has relations: molfunc_protein with CXCR2, molfunc_protein with CXCR2, molfunc_protein with CXCR1, molfunc_protein with CXCR1, molfunc_molfunc with C-X-C chemokine receptor activity, molfunc_molfunc with C-X-C chemokine receptor activity. A2B adenosine receptor binding has relations: molfunc_molfunc with adenosine receptor binding, molfunc_molfunc with adenosine receptor binding. insect larval thoracic segment has relations: anatomy_anatomy with insect larval prothoracic segment, anatomy_anatomy with insect larval prothoracic segment. Definitions: IL-8 defined as following: Binding to an interleukin-8 receptor. [GOC:go_curators]. 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.. tT4 defined as following: An orally bioavailable antagonist of the immunomodulatory checkpoint molecule adenosine A2B receptor (A2BR; ADORA2B), with potential anti-inflammatory, immunomodulating and antineoplastic activities. Upon oral administration, A2BR antagonist TT-4 competes with adenosine for binding to A2BR expressed on various cancer cell types and numerous immune cells, such as dendritic cells (DCs), mast cells, macrophages and lymphocytes. This inhibits A2BR activity and prevents adenosine/A2BR-mediated signaling. The inhibition of A2BR in cancer cells prevents activation of downstream oncogenic pathways, which leads to an inhibition of cell proliferation and metastasis. A2BR inhibition also prevents the release of various growth factors, cytokines and chemokines, such as vascular endothelial growth factor (VEGF), interleukin-8 (IL-8) and angiopoietin-2 (Ang2) from immune cells, which may abrogate the adenosine-mediated immunosuppression in the tumor microenvironment (TME) and activate the immune system to exert anti-tumor immune responses against cancer cells leading to tumor cell killing. In addition, under non-cancerous inflammatory conditions, inhibition of A2BR leads to reduced activation and proliferation of various immune cells, which results in decreased pro-inflammatory cytokine production and may prevent inflammation. A2BR, a G protein-coupled signaling receptor, is expressed on the cell surfaces of numerous immune cells and is often overexpressed on a variety of cancer cell types; it plays a key role in their proliferation, progression and metastasis. Adenosine is overproduced under inflammatory conditions and plays a key role in pro-inflammatory actions. Adenosine is often overproduced by tumor cells and plays a key role in immunosuppression and tumor cell proliferation. The pro- and anti-inflammatory effects of adenosine and A2BR are cell type-specific and dependent on the extracellular microenvironment..", "label": "yes"}
{"original_question": "Has proteomics been used in the study of the dry eye syndrome?", "id": "converted_35", "sentence1": "Has proteomics been used in the study of the dry eye syndrome?", "sentence2": "Tear proteomic analysis of patients with type 2 diabetes and dry eye syndrome by two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry. Dry eye syndrome in diabetic patients is associated with aberrant expression of tear proteins, and the findings could lead to identification of novel pathways for therapeutic targeting and new diagnostic markers.  2D electrophoresis (2DE) and Differential gel electrophoresis (DIGE) was done to identify differentially expressed proteins.  Two dimensional electrophoretic analysis of human tears: collection method in dry eye syndrome. Identification of tear fluid biomarkers in dry eye syndrome using iTRAQ quantitative proteomics. This study demonstrated that iTRAQ technology combined with 2D-nanoLC-nanoESI-MS/MS quantitative proteomics is a powerful tool for biomarker discovery.[SEP]Relations: dry eye syndrome has relations: disease_protein with STAT4, disease_protein with STAT4, disease_disease with syndromic disease, disease_disease with syndromic disease, disease_protein with TNIP1, disease_protein with TNIP1, disease_protein with PHIP, disease_protein with PHIP, disease_protein with TNFAIP3, disease_protein with TNFAIP3. Definitions: dry eye syndrome defined as following: Corneal and conjunctival dryness due to deficient tear production, predominantly in menopausal and post-menopausal women. Filamentary keratitis or erosion of the conjunctival and corneal epithelium may be caused by these disorders. Sensation of the presence of a foreign body in the eye and burning of the eyes may occur.. human defined as following: Members of the species Homo sapiens..", "label": "yes"}
{"original_question": "Are pseudogenes enriched with housekeeping protein families?", "id": "converted_36", "sentence1": "Are pseudogenes enriched with housekeeping protein families?", "sentence2": "housekeeping families tend to be enriched with a large number of pseudogenes[SEP]Definitions: pseudogenes defined as following: Genes bearing close resemblance to known genes at different loci, but rendered non-functional by additions or deletions in structure that prevent normal transcription or translation. When lacking introns and containing a poly-A segment near the downstream end (as a result of reverse copying from processed nuclear RNA into double-stranded DNA), they are called processed genes..", "label": "yes"}
{"original_question": "Is Calcium/Calmodulin dependent protein kinase II (CaMKII) involved in cardiac arrhythmias and heart failure?", "id": "converted_37", "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) \u03b4(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: 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 mice defined as following: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.. humans defined as following: Members of the species Homo sapiens.. 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).. 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.. calmodulin-dependent 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). CaMKII defined as following: This gene is involved in both protein phosphorylation and signaling.. 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.. 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.. cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. 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.. cell membrane defined as following: Any of the lipid bilayer membranes within a cell.. 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.. 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.. 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.. cardiac disease defined as following: Pathological conditions involving the HEART including its structural and functional abnormalities.. 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.. 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.. 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.. 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.. systolic heart failure defined as following: Heart failure caused by abnormal myocardial contraction during SYSTOLE leading to defective cardiac emptying.. 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.. 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.. 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.. 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). 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.. hyperactivity defined as following: Increased motor activity that is not goal directed.. 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 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.. 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.. myocardial ischemia defined as following: Thickening and loss of elasticity of the CORONARY ARTERIES, leading to progressive arterial insufficiency (CORONARY DISEASE).. 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.. myocardial hypertrophy defined as following: Thickening of the myocardium often due to chronic pressure overload.. 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.. Transgenic defined as following: Experimental organism whose genome has been altered by the transfer of a gene or genes from another species or breed..", "label": "yes"}
{"original_question": "Does cucumber lower blood sugar in diabetics?", "id": "converted_38", "sentence1": "Does cucumber lower blood sugar in diabetics?", "sentence2": "The ethanolic extract of Cucumis sativus Linn, Cucumis melo utilissimum Roxb, Cucumis melo Linn, Benincasa hispida Thunb Cogn and Tricosanthes anguina Nees, when administered in 250 mg/kg dose, orally to rats failed to lower blood sugar or to depress the peak value, after glucose load. Ethanolic extract of Tricosanthes dioica Roxb plant caused a significant lowering of blood sugar in fasted rats and depressed the peak value in glucose loaded single and longterm fed groups of rats. The ethanolic extract of the aerial part of T. dioica also induced significant depression in the peak values in the glucose loaded models. The amount of sucrose in ordinary marinated foods, such as herring, cucumber, and common beet was negligible Dietary saponins of sea cucumber ameliorate obesity, hepatic steatosis, and glucose intolerance in high-fat diet-fed mice. In this study, we investigated the effects of saponins of sea cucumber (SSC) on high-fat diet-induced obesity, insulin resistance, and fatty liver in mice. Mice administrated with 0.1% SSC had significantly decreased serum glucose and insulin levels, lower homeostatic model assessment for insulin resistance index, and area under the blood glucose curve, suggesting that insulin sensitivity is enhanced by dietary SSC. [Effects of sea cucumber cerebroside and its long-chain base on lipid and glucose metabolism in obese mice]. OBJECTIVE: To investigate the effect of sea cucumber cerebroside(SCC) and its long-chain base(LCB) on lipid and glucose metabolism in obese mice. CONCLUSIONS: Sea cucumber cerebroside and its long-chain base can improve the glucose and lipid metabolism in obese mice. The hitherto unknown glucose regulating role of three vegetable peels from cucurbitaceae family was evaluated. In a preliminary study, effects of ethanolic extracts of Cucurbita pepo, Cucumis sativus and Praecitrullus fistulosus peels were studied at 250 and 500\u00a0mg\u00a0kg(-1)\u00a0d(-1) for 15\u00a0days in the alterations in serum glucose and in hepatic lipid peroxidation (LPO) in male mice. All the three peel extracts nearly reversed most of these changes induced by alloxan suggesting their possible role in ameliorating diabetes mellitus and related changes in serum lipids. Antidiabetic activity of aqueous fruit extract of Cucumis trigonus Roxb. in streptozotocin-induced-diabetic rats. Cucumis trigonus Roxb. (Cucurbitaceae) fruit is used in the Indian traditional medicine for the treatment of diabetes. Based on a number of reports on the blood glucose level reduction and the other complications of diabetes associated with some Cucurbitaceae plants, the antidiabetic effect of Cucumis trigonus fruit was investigated. The antidiabetic activity of aqueous extract of Cucumis trigonus fruit was evaluated by using normal and streptozotocin-induced-diabetic rats. The aqueous fruit extract of Cucumis trigonus has had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced-diabetic rats. Possible amelioration of atherogenic diet induced dyslipidemia, hypothyroidism and hyperglycemia by the peel extracts of Mangifera indica, Cucumis melo and Citrullus vulgaris fruits in rats. Hitherto unknown efficacy of the peel extracts of Mangifera indica (MI), Cucumis melo (CM) and Citrullus vulgaris (CV) fruits in ameliorating the diet-induced alterations in dyslipidemia, thyroid dysfunction and diabetes mellitus have been investigated in rats. Rats, treated simultaneously with either of the peel extracts reversed the CCT-diet induced increase in the levels of tissue LPO, serum lipids, glucose, creatinine kinase-MB and decrease in the levels of thyroid hormones and insulin indicating their potential to ameliorate the diet induced alterations in serum lipids, thyroid dysfunctions and hyperglycemia/diabetes mellitus. Role of pectin from cucumber (Cucumis sativus) in modulation of protein kinase C activity and regulation of glycogen metabolism in rats. The regulatory role of protein kinase C (PKC) in glycogen metabolism in pectin fed rats was investigated. Administration of pectin (5 g/kg body wt/day) from cucumber (Cucumis sativius L.) led to inhibitory effects on PKC activity in the liver of rats. In the brain and pancreas, PKC activity was significantly higher in pectin-treated rats as compared to the control group. Level of blood glucose was significantly lowered and the level of glycogen in the liver was significantly increased in pectin-administered rats. Addition of fermented milk (yogurt) and pickled cucumber to a breakfast with a high-glycemic index bread significantly lowered postprandial glycemia and insulinemia compared with the reference meal. In contrast, addition of regular milk and fresh cucumber had no favorable effect on the metabolic responses. Tolbutamide, Cucurbita ficifolia, Phaseolus vulgaris, Opuntia streptacantha, Spinacea oleracea, Cucumis sativus and Cuminum cyminum decrease significantly the area under the glucose tolerance curve and the hyperglycemic peak. Two unsaturated fatty acids with potent \u03b1-glucosidase inhibitory activity purified from the body wall of sea cucumber (Stichopus japonicus). In this study, 2 fatty acids with strong \u03b1-glucosidase-inhibitory activity, 7(Z)-octadecenoic acid and 7(Z),10(Z)-octadecadienoic acid, were purified and identified from sea cucumber. Therefore, sea cucumber fatty acids can potentially be developed as a novel natural nutraceutical for the management of type-2 diabetes.[SEP]Relations: Glucose intolerance has relations: disease_phenotype_positive with Cushing disease due to pituitary adenoma, disease_phenotype_positive with Cushing disease due to pituitary adenoma, disease_phenotype_positive with diabetes mellitus (disease), disease_phenotype_positive with diabetes mellitus (disease). Tolbutamide has relations: indication with diabetes mellitus (disease), indication with diabetes mellitus (disease), drug_drug with Invert sugar, drug_drug with Invert sugar, indication with type 2 diabetes mellitus, indication with type 2 diabetes mellitus. Definitions: fatty liver defined as following: Lipid infiltration of the hepatic parenchymal cells resulting in a yellow-colored liver. The abnormal lipid accumulation is usually in the form of TRIGLYCERIDES, either as a single large droplet or multiple small droplets. Fatty liver is caused by an imbalance in the metabolism of FATTY ACIDS.. thyroid hormones defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs.. diabetes mellitus defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.. Sea cucumber defined as following: A class of Echinodermata characterized by long, slender bodies.. depressed defined as following: An emotional state characterized by feelings of sadness, emptiness, and/or tearfulness.. 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.. hepatic defined as following: Pertaining to, affecting, or associated with the liver.. lipid 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). cerebroside defined as following: Neutral glycosphingolipids that contain a monosaccharide, normally glucose or galactose, in 1-ortho-beta-glycosidic linkage with the primary alcohol of an N-acyl sphingoid (ceramide). In plants the monosaccharide is normally glucose and the sphingoid usually phytosphingosine. In animals, the monosaccharide is usually galactose, though this may vary with the tissue and the sphingoid is usually sphingosine or dihydrosphingosine. (From Oxford Dictionary of Biochemistry and Molecular Biology, 1st ed). 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). saponins defined as following: A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycone moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose.. 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.. Spinacea oleracea defined as following: A widely cultivated plant, native to Asia, having succulent, edible leaves eaten as a vegetable. (From American Heritage Dictionary, 1982). peels defined as following: Shedding of the outer layer of skin or mucosal tissue.. glucose defined as following: The determination of the amount of glucose present in a sample.. pectin defined as following: High molecular weight polysaccharides present in the cell walls of all plants. Pectins cement cell walls together. They are used as emulsifiers and stabilizers in the food industry. They have been tried for a variety of therapeutic uses including as antidiarrheals, where they are now generally considered ineffective, and in the treatment of hypercholesterolemia.. 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.. Tolbutamide defined as following: A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290). rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. alloxan defined as following: Acidic compound formed by oxidation of URIC ACID. It is isolated as an efflorescent crystalline hydrate.. 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.. glucose intolerance defined as following: A pathological state in which BLOOD GLUCOSE level is less than approximately 140 mg/100 ml of PLASMA at fasting, and above approximately 200 mg/100 ml plasma at 30-, 60-, or 90-minute during a GLUCOSE TOLERANCE TEST. This condition is seen frequently in DIABETES MELLITUS, but also occurs with other diseases and MALNUTRITION.. antidiabetic 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.. Cucumis melo defined as following: A plant species of the family CUCURBITACEAE, order Violales, subclass Dilleniidae known for the melon fruits with reticulated (net) surface including cantaloupes, honeydew, casaba, and Persian melons.. Phaseolus vulgaris defined as following: The plant species that provides kidney beans.. 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.. Cucurbitaceae defined as following: The gourd plant family of the order Violales, subclass Dilleniidae, class Magnoliopsida. It is sometimes placed in its own order, Cucurbitales. 'Melon' generally refers to CUCUMIS; CITRULLUS; or MOMORDICA.. 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..", "label": "yes"}
{"original_question": "Is Annexin V an apoptotic marker?", "id": "converted_39", "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., na\u00efve 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 &lt;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: apoptotic body has relations: cellcomp_cellcomp with extracellular vesicle, cellcomp_cellcomp with extracellular vesicle. 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. Definitions: 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]. 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.. 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.. 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.. 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.. Ki67 defined as following: This gene is involved in cellular proliferation.. hCG defined as following: A sialoglycoprotein hormone secreted by the placenta and maintains the corpus luteum at the beginning of the gestation period.. 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.. cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. 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.. 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.. annexin V defined as following: This gene is involved in anticoagulation processes and mediates lipid binding.. DR5 defined as following: Human TNFRSF10B wild-type allele is located within 8p22-p21 and is approximately 49 kb in length. This allele, which encodes tumor necrosis factor receptor superfamily member 10B protein, plays a role in tumor necrosis factor-related apoptosis signal mediation.. ofloxacin defined as following: A synthetic fluoroquinolone antibacterial agent that inhibits the supercoiling activity of bacterial DNA GYRASE, halting DNA REPLICATION.. 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.. cell surface defined as following: The external part of the cell wall and/or plasma membrane. [GOC:jl, GOC:mtg_sensu, GOC:sm]. PS defined as following: <p>Supernumerary mandibular right central primary incisor</p>. 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)]. rabbits defined as following: Taxonomic family which includes rabbits and hares.. cytoskeletal defined as following: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.. 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.. 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.. 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.. 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.. phosphatidylserine defined as following: A phospholipid with a polar serine found in phosphoester linkage to diacylglycerol.. 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.. 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.. 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.. 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.. 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.. 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.. Atherosclerotic defined as following: status similar or related to atherosclerosis. 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.. 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.. PI defined as following: Backflow of blood from the PULMONARY ARTERY into the RIGHT VENTRICLE due to imperfect closure of the PULMONARY VALVE.. 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]. germ cells defined as following: The reproductive cells in multicellular organisms at various stages during GAMETOGENESIS.. Annexin V defined as following: This gene is involved in anticoagulation processes and mediates lipid binding..", "label": "yes"}
{"original_question": "Is there an association between Muenke Syndrome and FGFR3 gene mutation?", "id": "converted_40", "sentence1": "Is there an association between Muenke Syndrome and FGFR3 gene mutation?", "sentence2": "RESULTS: Forty-four with a positive FGFR3 mutation, median age 9 years, range 7 months to 52 years were enrolled. In addition, 10 unaffected siblings served as controls (5 males, 5 females; median age, 13 years; range, 3-18 years). Muenke is a fibroblast growth factor receptor 3 (FGFR-3)-associated syndrome, which was first described in late 1990 s.  The syndrome is defined molecularly by a unique point mutation c.749C>G in exon 7 of the FGFR3 gene which results to an amino acid substitution p.Pro250Arg of the protein product.  Muenke syndrome caused by point mutation (C749G) in the FGFR3 gene affects 1 in 30,000 newborns and accounts for 25% to 30% of genetic causes of craniosynostosis. Phenotypic variability in two families of Muenke syndrome with FGFR3 mutation. PURPOSE: There are a number of craniosynostosis syndromes with hearing loss-including Muenke, Apert, Pfeiffer, Crouzon, Beare-Stevenson, Crouzon with acanthosis nigricans, and Jackson-Weiss syndromes-that result from mutations in the fibroblast growth factor receptor (FGFR) genes.  Muenke syndrome is an autosomal dominant craniosynostosis syndrome resulting from a defining point mutation in the Fibroblast Growth Factor Receptor3 (FGFR3) gene. Talocalcaneal coalition in Muenke syndrome: report of a patient, review of the literature in FGFR-related craniosynostoses, and consideration of mechanism. To better understand the pathophysiology of the Muenke syndrome, we present collective findings from several recent studies that have characterized a genetically equivalent mouse model for Muenke syndrome (FgfR3 (P244R)) and compare them with human phenotypes. We show in this study that knock-in mice harboring the mutation responsible for the Muenke syndrome (FgfR3(P244R)) display postnatal shortening of the cranial base along with synchondrosis growth plate dysfunction characterized by loss of resting, proliferating and hypertrophic chondrocyte zones and decreased Ihh expression. Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes. Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis. Muenke syndrome (FGFR3-related craniosynostosis): expansion of the phenotype and review of the literature. The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes. PURPOSE: The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 years ago, represents the single most common craniosynostosis mutation. The heterozygous Pro250Arg substitution mutation in fibroblast growth factor receptor 3 (FGFR3), which increases ligand-dependent signalling, is the most common genetic cause of craniosynostosis in humans and defines Muenke syndrome. P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities. Muenke syndrome caused by the FGFR3 Pro250Arg mutation is associated with craniosynostosis, hearing loss, and various bony anomalies. Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. Muenke syndrome, defined by heterozygosity for a Pro250Arg substitution in fibroblast growth factor receptor 3 (FGFR3), is the most common genetic cause of craniosynostosis in humans. In addition, sensorineural hearing loss is detected in all FgfR3 (P244R) mutant mice as in the majority of Muenke syndrome patients. Genetic testing identifies a pathogenic mutation or chromosomal abnormality in \u223c 21% of cases, but it is likely that further causative mutations remain to be discovered.To identify a shared signature of genetically determined craniosynostosis by comparing the expression patterns in three monogenic syndromes with a control group of patients with non-syndromic sagittal synostosis.Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured The craniosynostosis syndromes: Apert syndrome, Beare-Stevenson syndrome, Crouzon syndrome, Jackson-Weiss syndrome, Muenke syndrome, Pfeiffer syndrome and Saethre-Chotzen syndrome can be caused by mutation in either FGFR1, FGFR2, or FGFR3 Identical proline-->arginine gain-of-function mutations in fibroblast growth factor receptor (FGFR) 1 (Pro252Arg), FGFR2 (Pro253Arg) and FGFR3 (Pro250Arg), result in type I Pfeiffer, Apert and Muenke craniosynostosis syndromes, respectively The Pro250Arg mutation in the FGFR3 gene is found in patients with Muenke syndrome and is one of the most frequently encountered mutations in craniosynostosis syndromes Mutation analysis of FGFR-3 revealed a missense mutation in exon 6, c.749 C>G, with a resultant amino acid change from proline to arginine at codon 250 (P250R), in keeping with Muenke syndrome (Am J Hum Genet 1997;60:555-564) In an attempt to delineate functional features separating SCS from Muenkes syndrome, we screened patients presenting with coronal suture synostosis for mutations in the TWIST 1 gene, and for the Pro250Arg mutation in FGFR3 Since the Gly380Arg achondroplasia mutation was recognized, similar observations regarding the conserved nature of FGFR mutations and resulting phenotype have been made regarding other skeletal phenotypes, including hypochondroplasia, thanatophoric dysplasia, and Muenke coronal craniosynostosis Mutations in the gene that encodes Fibroblast Growth Factor Receptor 3 (FGFR3) are associated with Achondroplasia (MIM 100800), Hypochondroplasia (MIM 146000), Muenke Syndrome (MIM 602849), Thanatophoric Dysplasia (MIM 187600, MIM 187601) and Lacrimo-Auriculo-Dento-Digital Syndrome (MIM 149730).Here we report a clinical and molecular study in a large cohort of 125 Portuguese patients with these skeletal disorders.  The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene.  P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities.  METHODS: Fibroblasts from 10 individuals each with Apert syndrome (FGFR2 substitution S252W), Muenke syndrome (FGFR3 substitution P250R), Saethre-Chotzen syndrome (various mutations in TWIST1) and non-syndromic sagittal synostosis (no mutation detected) were cultured.  Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene.  Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3).  In spite of a variable phenotype, Muenke syndrome has been related to a unique mutation on the FGFR3 gene, Pro 250 to Arg, which is characteristic of this disease.  Skeletal analysis of the Fgfr3(P244R) mouse, a genetic model for the Muenke craniosynostosis syndrome. Muenke syndrome is caused by a single defining point mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. Epilepsy in Muenke syndrome: FGFR3-related craniosynostosis. Muenke syndrome, also known as FGFR3-associated coronal synostosis, is defined molecularly by the presence of a heterozygous nucleotide transversion, c.749C>G, encoding the amino acid substitution Pro250Arg, in the fibroblast growth factor receptor type 3 gene (FGFR3). The Muenke syndrome mutation (FGFR3 (P250R)), which was discovered 15 years ago, represents the single most common craniosynostosis mutation.[SEP]Relations: Muenke syndrome has relations: disease_protein with FGFR3, disease_protein with FGFR3. FGFR3 has relations: disease_protein with Muenke syndrome, disease_protein with Muenke syndrome, disease_protein with apert syndrome, disease_protein with apert syndrome, disease_protein with LADD syndrome, disease_protein with LADD syndrome. apert syndrome has relations: disease_protein with FGFR3, disease_protein with FGFR3. 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.. P250R mutation defined as following: A change in the nucleotide sequence of the ARID1B gene.. 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.. Beare-Stevenson syndrome defined as following: A rare, autosomal dominant inherited disorder caused by mutations in the FGFR2 gene. It is characterized by the premature fusion of the bones of the skull (craniosynostosis) and a skin abnormality called cutis gyrata. The craniosynostosis results in a cloverleaf-shaped skull, wide-set eyes, ear abnormalities, underdeveloped upper jaw, and developmental delays. Cutis gyrata is characterized by a wrinkled skin appearance, especially on the face, near the ears, and on the palms and soles.. humans defined as following: Members of the species Homo sapiens.. Fibroblast Growth Factor Receptor 3 defined as following: A fibroblast growth factor receptor with specificity for FIBROBLAST GROWTH FACTORS; HEPARAN SULFATE PROTEOGLYCAN; and NEURONAL CELL ADHESION MOLECULES. Several variants of the receptor exist due to multiple ALTERNATIVE SPLICING of its mRNA. Fibroblast growth factor receptor 1 contains three extracellular IMMUNOGLOBULIN C2-SET DOMAINS and is a tyrosine kinase that transmits signals through the MAP KINASE SIGNALING SYSTEM.. 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.. 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.. 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). arginine defined as following: An essential amino acid that is physiologically active in the L-form.. Arg defined as following: This gene plays a role in signal transduction.. P250R defined as following: Human ARID1B wild-type allele is located in the vicinity of 6q25.1 and is approximately 433 kb in length. This allele, which encodes AT-rich interactive domain-containing protein 1B, is involved in both cell type-specific transcriptional regulation and chromatin remodeling.. FGFR 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.. 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.. 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.. thanatophoric dysplasia defined as following: Thanatophoric dysplasia characterized by a normally shaped skull and curved femurs. It is the most common type of thanatophoric dysplasia.. 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.. 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.. craniosynostosis defined as following: A form of syndromic craniosynostosis with characteristics of highly variable craniosynostosis with frontal bossing, turribrachycephaly and cloverleaf skull anomaly. Hypoplasia of the supraorbital ridges, cleft palate, extra teeth and limb anomalies has also been described. Associated problems include headache, poor vision, and seizures. Intelligence is normal.. Hypochondroplasia defined as following: An autosomal dominant disorder that is often caused by a defect in fibroblast growth factor receptor 3, and characterized by short stature, micromelia, and a comparatively large head. The features are milder than those seen in achondroplasia.. FGFR3 gene defined as following: This gene plays a role in bone development and maintenance and mutations in the gene are associated with craniosynostosis and several types of skeletal dysplasia.. autosomal dominant disorder defined as following: An inherited disorder that manifests when one copy of a mutated gene is present.. proline defined as following: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.. TWIST1 defined as following: Twist-related protein 1 (202 aa, ~21 kDa) is encoded by the human TWIST1 gene. This protein plays a role in the negative regulation of both transcription and myogenesis.. coronal suture synostosis defined as following: Premature closure of the coronal suture of skull. [HPO:probinson]. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. Pfeiffer syndrome defined as following: An autosomal dominant inherited type of acrocephalosyndactyly caused by mutations in the FGFR1 or FGFR2 genes. It is characterized by early closure of the sutures between the skull bones, bulging and wide-set eyes, broad thumbs, big toes, and partial syndactyly in the hands and toes.. amino acid substitution 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.. cranial base defined as following: The inferior region of the skull consisting of an internal (cerebral), and an external (basilar) surface.. FGFR2 defined as following: A fibroblast growth factor receptor which contains three extracellular IMMUNOGLOBULIN I-SET DOMAINS and is expressed as two isoforms. One receptor isoform is expressed in the MESENCHYME and is activated by FIBROBLAST GROWTH FACTOR 2. A second isoform is expressed mainly by EPITHELIAL CELLS and is activated by FIBROBLAST GROWTH FACTOR 7 and FIBROBLAST GROWTH FACTOR 10. Mutation of the gene for fibroblast growth factor receptor 2 can result in craniosynostotic syndromes (e.g., APERT SYNDROME; and CROUZON SYNDROME).. 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.. Jackson-Weiss syndrome defined as following: A rare, autosomal dominant inherited disorder caused by mutations in the FGFR2 gene. It is characterized by the premature fusion of the bones of the skull (craniosynostosis) and foot abnormalities. The craniosynostosis results in a malformed skull, widely spaced eyes, and a bulging forehead. The foot abnormalities consist of short and wide first toes, which bend away from the other toes. In addition, syndactyly in some toes may be present. The hands are almost always normal.. craniosynostosis syndromes defined as following: Premature closure of one or more CRANIAL SUTURES. It often results in plagiocephaly. Craniosynostoses that involve multiple sutures are sometimes associated with congenital syndromes such as ACROCEPHALOSYNDACTYLIA; and CRANIOFACIAL DYSOSTOSIS.. Muenke Syndrome defined as following: A rare autosomal dominant inherited disorder caused by mutations in the FGFR3 gene. It is characterized by premature fusion of cranial bones, resulting in head shape abnormalities, flattened cheekbones, and wide-set eyes.. 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). chondrocyte defined as following: Polymorphic cells that form cartilage.. craniofacial defined as following: refers to the bones of the skull and face.. 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.. FGFR3 gene mutation defined as following: A change in the nucleotide sequence of the FGFR3 gene..", "label": "yes"}
{"original_question": "Has whole exome sequencing been performed in Alzheimer patients?", "id": "converted_41", "sentence1": "Has whole exome sequencing been performed in Alzheimer patients?", "sentence2": "Pilot whole-exome sequencing of a German early-onset Alzheimer's disease cohort reveals a substantial frequency of PSEN2 variants. We performed whole-exome sequencing in early-onset Alzheimer disease (EOAD) and late-onset Alzheimer disease (LOAD) families followed by functional studies of select variants. Whole-exome sequencing revealed a nonsense mutation in PRNP (NM_000311, c.C478T; p.Q160*; rs80356711) associated with homozygosity for the V allele at position 129 of the protein, further highlighting how very similar genotypes in PRNP result in strikingly different phenotypes. In the search for new genes in Alzheimer's disease, classic linkage-based and candidate-gene-based association studies have been supplanted by exome sequencing, genome-wide sequencing (for mendelian forms of Alzheimer's disease), and genome-wide association studies (for non-mendelian forms).  We performed whole exome sequencing in a Turkish patient clinically diagnosed with Alzheimer's disease from a consanguineous family  Performing exome sequencing in 14 autosomal dominant early-onset Alzheimer disease (ADEOAD) index cases without mutation on known genes (amyloid precursor protein (APP), presenilin1 (PSEN1) and presenilin2 (PSEN2)), we found that in five patients, the SORL1 gene harbored unknown nonsense (n=1) or missense (n=4) mutations[SEP]Relations: Alzheimer disease has relations: disease_protein with PLAU, disease_protein with PLAU, disease_protein with ARC, disease_protein with ARC, disease_protein with NOS3, disease_protein with NOS3, disease_protein with MIR100, disease_protein with MIR100, disease_protein with ABI3, disease_protein with ABI3. 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.. 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.. 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.. 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.. APP defined as following: An application designed specifically for use on a smartphone.. 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.. 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.. SORL1 gene defined as following: This gene is involved in both endocytosis and protein sorting.. genotypes defined as following: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.. PSEN2 defined as following: Presenilin-2 (448 aa, ~50 kDa) is encoded by the human PSEN2 gene. This protein is involved in proteolytic processing.. LOAD defined as following: Any device that draws current from an electrical system.. 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"}
{"original_question": "Is Stat4 a transcription factor?", "id": "converted_42", "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). molecules defined as following: An aggregate of two or more atoms in a defined arrangement held together by chemical bonds.. 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.. 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"}
{"original_question": "Do IEG create a ripple effect of transcription?", "id": "converted_43", "sentence1": "Do IEG create a ripple effect of transcription?", "sentence2": "Rapid induction of immediate-early genes (IEGs) in response to growth factor stimulations is accompanied by co-upregulation of their neighbouring genes. Even in surrounding intergenic regions, transcriptional activation took place at the same time.  Here we show that intensive transcription at one locus frequently spills over into its physical neighbouring loci. Ripples from neighbouring transcription. Ripples from neighbouring transcription.[SEP]Relations: insect neurogenic region has relations: anatomy_anatomy with embryonic structure, anatomy_anatomy with embryonic structure. 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.. immediate-early genes defined as following: Genes that show rapid and transient expression in the absence of de novo protein synthesis. The term was originally used exclusively for viral genes where immediate-early referred to transcription immediately following virus integration into the host cell. It is also used to describe cellular genes which are expressed immediately after resting cells are stimulated by extracellular signals such as growth factors and neurotransmitters.. 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"}
{"original_question": "Do T-Cells regulate neuropathic pain?", "id": "converted_44", "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.<CopyrightInformation>Copyright \u00a9 2012 International Association for the Study of Pain Recent studies show that T cells play an important role in neuropathic pain following nerve injury in rats These results show a peripheral pivotal role of CatS in the development of neuropathic pain through the antigen-specific activation of CD4(+) T-cells Chemokine (C-C motif) ligand 1 (CCL-1), a well-characterized chemokine secreted by activated T cells, has been shown to play an important role in neuropathic pain induced by nerve injury and is also produced in various cell types in the CNS, especially in dorsal root ganglia (DRG) In the present study, we investigated systemic T-cell subset responses and T-cell related cytokine profiles in patients with chronic neuropathic pain. Anti-inflammatory T-cell shift in neuropathic pain. Thus, this T-cell subset may be specifically targeted to alleviate chronic neuropathic pain.. Regulatory T cells attenuate neuropathic pain following peripheral nerve injury and experimental autoimmune neuritis. Macrophage-T cell interactions mediate neuropathic pain through the glucocorticoid-induced tumor necrosis factor ligand system.[SEP]Relations: neuropathy, painful has relations: disease_phenotype_positive with Peripheral neuropathy, disease_phenotype_positive with Peripheral neuropathy, disease_protein with THBD, disease_protein with THBD, disease_phenotype_positive with Fever, disease_phenotype_positive with Fever, disease_phenotype_positive with Skeletal muscle atrophy, disease_phenotype_positive with Skeletal muscle atrophy. Chronic pain has relations: phenotype_phenotype with Pain, phenotype_phenotype with Pain. Definitions: nerve injury defined as following: Injury to nervous tissue.. rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. GITRL defined as following: Human TNFSF18 wild-type allele is located in the vicinity of 1q25.1 and is approximately 11 kb in length. This allele, which encodes tumor necrosis factor ligand superfamily member 18 protein, is involved in the positive regulation of T-cell survival.. 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.. 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.. 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.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. CatS 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). peripheral nerve injury defined as following: Injuries to the PERIPHERAL NERVES.. peripheral defined as following: On or near an edge or constituting an outer boundary; the outer area.. DRG defined as following: A system for classifying patient care by relating common characteristics such as diagnosis, treatment, and age to an expected consumption of hospital resources and length of stay. Its purpose is to provide a framework for specifying case mix and to reduce hospital costs and reimbursements and it forms the cornerstone of the prospective payment system.. neuropathic pain defined as following: Chronic pain caused by damage to nerve fibers. It is usually associated with tissue injury.. 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..", "label": "yes"}
{"original_question": "Do histone variant mH2A (macro-H2A) levels decrease upon differentiation?", "id": "converted_45", "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 na\u00efve 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.. regulatory regions defined as following: Nucleic acid sequences involved in regulating the expression of genes.. 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.. 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.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. somatic cells defined as following: Nucleated cell which has one or more diploid sets (46 pairs) of chromosomes.. 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.. 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.. 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"}
{"original_question": "Is H4K20 methylation associated with DNA replication?", "id": "converted_46", "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. <CopyrightInformation>\u00a9 2016 by The American Society for Biochemistry and Molecular Biology, Inc.</C Thus, coordinating the status of H4K20 methylation is pivotal for the proper selection of DNA replication origins in higher eukaryotes.. 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.[SEP]Relations: histone H4 acetylation has relations: bioprocess_protein with MORF4L2, bioprocess_protein with MORF4L2, bioprocess_protein with ACTL6B, bioprocess_protein with ACTL6B, bioprocess_protein with MORF4L1, bioprocess_protein with MORF4L1, bioprocess_bioprocess with histone H4 acetylation involved in response to DNA damage stimulus, bioprocess_bioprocess with histone H4 acetylation involved in response to DNA damage stimulus, bioprocess_protein with NAA50, bioprocess_protein with NAA50. Definitions: PR-Set7 defined as following: Human KMT5A wild-type allele is located in the vicinity of 12q24.31 and is approximately 26 kb in length. This allele, which encodes N-lysine methyltransferase KMT5A protein, is involved in protein methylation and chromatin modification.. lysine defined as following: An essential amino acid. It is often added to animal feed.. 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.. 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.. ORC defined as following: A multisubunit complex that is located at the replication origins of a chromosome. [GOC:elh]. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. genome defined as following: Anatomical set of genes in all the chromosomes.. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. 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). histone modifications defined as following: The covalent alteration of one or more amino acid residues within a histone protein. [GOC:krc].", "label": "yes"}
{"original_question": "Is Dupilumab used for treatment of atopic dermatitis?", "id": "converted_47", "sentence1": "Is Dupilumab used for treatment of atopic dermatitis?", "sentence2": "Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell-mediated diseases. Background 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. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. Dupilumab is a biologic agent targeted at TH2 cytokines, but indirectly impacts IgE and is an important biologic agent for atopic disease. Dupilumab for the treatment of atopic dermatitis: A clinical trial review. Dupilumab is a novel monoclonal antibody that was recently studied in adult patients with moderate-to-severe AD. Patients treated with dupilumab had marked and rapid improvement in all the evaluated measures of atopic dermatitis disease activity. The robust effects of dupilumab on skin inflammation and pruritus confirm the pathogenic role of IL-4 and IL-13 signaling in adult AD, and further support the application of Th2 cytokine antagonists in the treatment of this disease.[SEP]Relations: Dupilumab has relations: indication with dermatitis, atopic, indication with dermatitis, atopic, indication with atopic eczema, indication with atopic eczema, drug_drug with Dusigitumab, drug_drug with Dusigitumab, drug_drug with Teplizumab, drug_drug with Teplizumab. dermatitis, atopic has relations: indication with Dupilumab, indication with Dupilumab. 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). 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.. 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.. 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.. pruritus defined as following: A sensory perception which causes the desire or reflex to scratch. [PMID:26015312, PMID:29723501, PMID:30734045, Wikipedia:Itch]. atopic dermatitis defined as following: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed).. IgE defined as following: An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).. 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).. human defined as following: Members of the species Homo sapiens.. 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). 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"}
{"original_question": "Has the gorilla genome been determined?", "id": "converted_48", "sentence1": "Has the gorilla genome been determined?", "sentence2": "Starting with human, chimpanzee, gorilla, and orangutan genomes, our software generated an exhaustive data set of 292 ALs (\u223c1 kb each) in \u223c3 h.  We generated a high-quality assembly of the gorilla genome using single-molecule, real-time sequence technology and a string graph de novo assembly algorithm Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. DNA sequencing reveals that the genomes of the human, gorilla and chimpanzee share more than 98% homology.[SEP]Definitions: chimpanzee defined as following: The common chimpanzee, a species of the genus Pan, family HOMINIDAE. It lives in Africa, primarily in the tropical rainforests. There are a number of recognized subspecies.. 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.. human defined as following: Members of the species Homo sapiens.. 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.. gorilla defined as following: This single species of Gorilla, which is a member of the HOMINIDAE family, is the largest and most powerful of the PRIMATES. It is distributed in isolated scattered populations throughout forests of equatorial Africa..", "label": "yes"}
{"original_question": "Can methylenetetrahydrofolate reductase (MTHFR) gene mutations cause homocystinuria?", "id": "converted_49", "sentence1": "Can methylenetetrahydrofolate reductase (MTHFR) gene mutations cause homocystinuria?", "sentence2": "Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive disorder.  Several mutations seen in methylenetetrahydrofolate reductase (MTHFR) give rise to the formation of hyperhomocysteinemia and homocystinuria, a considerable risk factor for cardiovascular and cerebrovascular disorders, by leading to enzymatic inactivation. At admission, he had significantly elevated plasma and urine levels of total homocysteine, significantly decreased levels of folate in serum and cerebrospinal fluid, and a normal blood concentration of methionine. Response to treatment demonstrated B(6)-non-responsive homocystinuria. Molecular study showed compound heterozygous T353\u00a0N and D444\u00a0N mutations of the cystathionine beta-synthase (CBS) gene, and also a C667T homozygous mutation of the methylenetetrahydrofolate-reductase (MTHFR) gene.  Our case is atypical because of the absence of thromboembolism and the mild phenotype, in spite of being B(6)-non-responsive, and the association of a rare compound heterozygous mutation of the CBS gene and also an homozygous mutation of the MTHFR gene. Molecular characterization of five patients with homocystinuria due to severe methylenetetrahydrofolate reductase deficiency. Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in folate and homocysteine metabolism. Research performed during the past decade has clarified our understanding of MTHFR deficiencies that cause homocystinuria or mild hyperhomocysteinemia. Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the regulation of plasma homocysteine levels. MTHFR deficiency, an autosomal recessive disorder, results in homocystinuria and hypomethioninaemia and presents with highly variable symptoms affecting many organs but predominantly the central nervous system.  Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria. Rare mutations in the MTHFR gene have been associated with autosomal recessive MTHFR deficiency leading to homocystinuria. Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria. Five patients suspected of having non-classical homocystinuria due to MTHFR deficiency were examined with respect to their symptoms, MTHFR enzyme activity and genotypes of the MTHFR gene. The results of our study render the full-length characterisation of affected alleles in severe homocystinuria and moderate hyperhomocysteinaemia due to MTHFR deficiency and provide a basis for investigating the regulation of the human MTHFR gene. Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia. Different MTHFR mutations lead either to severe homocystinuria as a multisystem disorder or to moderate hyperhomocysteinaemia, which is a common risk factor for disorders ranging from cardiovasculopathy to spina bifida. We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis. On the contrary, thermolabile MTHFR caused by the 677C-->T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR. We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis. Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene The 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinemia, but this polymorphism does not seem to be a risk factor for venous thrombosis Hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene mutation have been postulated as a possible cause of recurrent miscarriage (RM) The 677C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinaemia We studied 24 patients with homocystinuria caused by homozygous CBS deficiency from 18 unrelated kindreds for FVL and for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and investigated their possible interaction in the risk of venous thrombosis.  AIM: Some methylenetetrahydrofolate reductase (MTHFR) gene mutations cause hyperhomocysteinemia and homocystinuria.  Betaine for treatment of homocystinuria caused by methylenetetrahydrofolate reductase deficiency. Severe deficiency of methylenetetrahydrofolate reductase (MTHFR) with homocystinuria can result in early demise or later-onset neurological impairment, including developmental delay, motor dysfunction, and seizures.  Deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR) leads to deficient remethylation of homocysteine and is one of the causes of homocystinuria.  Neurological disturbances have been described in homocystinuria caused by severe MTHFR deficiency.  The 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinemia, but this polymorphism does not seem to be a risk factor for venous thrombosis. Research performed during the past decade has clarified our understanding of MTHFR deficiencies that cause homocystinuria or mild hyperhomocysteinemia. The 677C>T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is an important cause of mild hyperhomocysteinaemia. The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Our cloning of the MTHFR coding sequence was initially followed by the identification of the first deleterious mutations in MTHFR, in patients with homocystinuria and marked hyperhomocysteinemia. Characterization of six novel mutations in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with homocystinuria. Molecular characterization of five patients with homocystinuria due to severe methylenetetrahydrofolate reductase deficiency. On the contrary, thermolabile MTHFR caused by the 677C-->T mutation, was frequently observed among homocystinuria patients, especially among those with thromboembolic complications: three of six homocystinuria patients who had suffered from a thromboembolic event had thermolabile MTHFR.[SEP]Relations: homocystinuria due to methylene tetrahydrofolate reductase deficiency has relations: disease_protein with MTHFR, disease_protein with MTHFR, disease_phenotype_positive with Thromboembolic stroke, disease_phenotype_positive with Thromboembolic stroke, disease_phenotype_positive with Hydrocephalus, disease_phenotype_positive with Hydrocephalus, disease_phenotype_positive with Ventriculomegaly, disease_phenotype_positive with Ventriculomegaly, disease_phenotype_positive with Autosomal recessive inheritance, disease_phenotype_positive with Autosomal recessive inheritance. Definitions: 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.\". mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. methylenetetrahydrofolate reductase defined as following: This gene is involved in folate metabolism and methionine biosynthesis.. methionine defined as following: A preparation of METHIONINE that includes a mixture of D-methionine and L-methionine isomers.. hyperhomocysteinaemia defined as following: Condition in which the plasma levels of homocysteine and related metabolites are elevated (>13.9 \u03bcmol/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.. folate defined as following: A cofactor for 1-carbon transfer involved with DNA synthesis.. 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.. venous thrombosis defined as following: The formation or presence of a blood clot (THROMBUS) within a vein.. CBS gene defined as following: This gene plays a role in transsulfuration.. thromboembolism defined as following: Obstruction of a blood vessel (embolism) by a blood clot (THROMBUS) in the blood stream.. 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.. gene mutation defined as following: A change in the nucleotide sequence of the TAF1 gene.. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. 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.. 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.. homocysteine defined as following: A thiol-containing amino acid formed by a demethylation of METHIONINE.. genotypes defined as following: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.. autosomal recessive disorder defined as following: An inherited disorder manifested only when two copies of a mutated gene are present.. 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.. FVL defined as following: Human F5 Leiden allele is a variant form of the F5 gene that is located in the vicinity of 1q23 and is approximately 75 kb in length. This allele, which encodes coagulation factor V Leiden protein, is involved in hypercoagulability due to resistance to degradation by activated protein C.. spina bifida defined as following: Congenital defects of closure of one or more vertebral arches, which may be associated with malformations of the spinal cord, nerve roots, congenital fibrous bands, lipomas, and congenital cysts. These malformations range from mild (e.g., SPINA BIFIDA OCCULTA) to severe, including rachischisis where there is complete failure of neural tube and spinal cord fusion, resulting in exposure of the spinal cord at the surface. Spinal dysraphism includes all forms of spina bifida. The open form is called SPINA BIFIDA CYSTICA and the closed form is SPINA BIFIDA OCCULTA. (From Joynt, Clinical Neurology, 1992, Ch55, p34). homocystinuria defined as following: Autosomal recessive inborn error of methionine metabolism usually caused by a deficiency of CYSTATHIONINE BETA-SYNTHASE and associated with elevations of homocysteine in plasma and urine. Clinical features include a tall slender habitus, SCOLIOSIS, arachnodactyly, MUSCLE WEAKNESS, genu varus, thin blond hair, malar flush, lens dislocations, an increased incidence of MENTAL RETARDATION, and a tendency to develop fibrosis of arteries, frequently complicated by CEREBROVASCULAR ACCIDENTS and MYOCARDIAL INFARCTION. (From Adams et al., Principles of Neurology, 6th ed, p979). 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.. MTHFR defined as following: A flavoprotein amine oxidoreductase that catalyzes the reversible conversion of 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. This enzyme was formerly classified as EC 1.1.1.171.. gene 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"}
{"original_question": "Does the TOP2B/TOP2A expression ratio affect the response to AML chemotherapy?", "id": "converted_50", "sentence1": "Does the TOP2B/TOP2A expression ratio affect the response to AML chemotherapy?", "sentence2": "High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype. Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy. Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005) High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia. Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005).Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype CONCLUSION: Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype. Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype.. High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia. Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005). Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy.[SEP]Relations: acute promyelocytic leukemia has relations: disease_protein with IRF2BP2, disease_protein with IRF2BP2, disease_protein with DAPK2, disease_protein with DAPK2, disease_protein with TET2, disease_protein with TET2, disease_protein with PML, disease_protein with PML, disease_protein with ITGB2, disease_protein with ITGB2. Definitions: TOP2A defined as following: DNA topoisomerase 2-alpha (1531 aa, ~174 kDa) is encoded by the human TOP2A gene. This protein is involved in the modulation of DNA topology.. 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.. HR defined as following: The rapid, localized death of plant cells in response to invasion by a pathogen. [ISBN:0582227089]. 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"}
{"original_question": "Is Beta-Thalassemia is associated with a mutation or deletion of the gene that codes for alpha globin?", "id": "converted_51", "sentence1": "Is Beta-Thalassemia is associated with a mutation or deletion of the gene that codes for alpha globin?", "sentence2": "Beta-thalassemia, one of the most common single-gene disorders, is the result of reduced or absent production of \u03b2-globin chains The beta-thalassemia syndromes are a heterogeneous group of genetic disorders characterized by reduced or absent expression of the beta-globin gene[SEP]Relations: beta thalassemia has relations: disease_disease with thalassemia, disease_disease with thalassemia, disease_phenotype_positive with Abnormal hemoglobin, disease_phenotype_positive with Abnormal hemoglobin, disease_protein with HBG1, disease_protein with HBG1, disease_phenotype_positive with Reduced hemoglobin A, disease_phenotype_positive with Reduced hemoglobin A, disease_disease with beta-thalassemia and related diseases, disease_disease with beta-thalassemia and related diseases. Definitions: beta-globin gene defined as following: Human HBB wt allele is located in the vicinity of 11p15.5 and is approximately 4 kb in length. This allele, which encodes hemoglobin subunit beta protein, plays a role in the transport of oxygen to tissues of the body. Mutations in this gene are associated with beta-thalassemia.. 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.. 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.. alpha globin defined as following: Hemoglobin subunit alpha (142 aa, ~15 kDa) is encoded by both the human HBA1 and human HBA2 genes. This protein plays a role in the distribution of oxygen from the lungs to other organs and tissues.. 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.. 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"}
{"original_question": "Is Cri Du Chat associated with an expansion of a repeat with in the gene found on chromosome 5?", "id": "converted_52", "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: 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). 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-).. chromosome 5 defined as following: One of the two pairs of human chromosomes in the group B class (CHROMOSOMES, HUMAN, 4-5).. 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). hypotonia defined as following: A diminution of the skeletal muscle tone marked by a diminished resistance to passive stretching.. 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.. 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.. 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.. 5p15 defined as following: A chromosome band present on 5p.. 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"}
{"original_question": "Is hydroxyurea usually used to treated infectious disease?", "id": "converted_53", "sentence1": "Is hydroxyurea usually used to treated infectious disease?", "sentence2": "Hydroxyurea represents the only available disease-modifying therapy for SCA, and has proven safety and efficacy in high-resource countries In conclusion, the data here presented suggests that hydroxyurea may prevent priapism attacks in sickle cell disease, probably at higher doses than usually prescribed for painful crisis prevention.. Clinical follow-up of hydroxyurea-treated adults with sickle cell disease. t may also attenuate optimal response to hydroxyurea therapy, the only effective and practical treatment option for SCD in sub-Saharan Africa Hydroxyurea is one of the most successfully used therapies for sickle cell disease Clinical experience with hydroxyurea for patients with sickle cell disease (SCD) has been accumulating for the past 25 years. The bulk of the current evidence suggests that hydroxyurea is well-tolerated, safe, and efficacious for most patients with SCD[SEP]Relations: Hydroxyurea has relations: contraindication with anemia (disease), contraindication with anemia (disease), contraindication with kidney disease, contraindication with kidney disease, indication with sickle cell disease and related diseases, indication with sickle cell disease and related diseases, drug_drug with Hepatitis A Vaccine, drug_drug with Hepatitis A Vaccine, drug_effect with Fever, drug_effect with Fever. Definitions: Hydroxyurea defined as following: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.. SCA 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.. SCD defined as following: Schnyder corneal dystrophy (SCD) is a rare form of stromal corneal dystrophy (see this term) characterized by corneal clouding or crystals within the corneal stroma, and a progressive decrease in visual acuity.. sickle cell disease defined as following: A disease characterized by chronic hemolytic anemia, episodic painful crises, and pathologic involvement of many organs. It is the clinical expression of homozygosity for hemoglobin S.. infectious disease 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.. hydroxyurea defined as following: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase..", "label": "no"}
{"original_question": "Does the histone chaperone ASF1 interact with histones H1/H2?", "id": "converted_54", "sentence1": "Does the histone chaperone ASF1 interact with histones H1/H2?", "sentence2": "The C terminus of the histone chaperone Asf1 cross-links to histone H3 in yeast and promotes interaction with histones H3 and H4. The central histone H3/H4 chaperone Asf1 comprises a highly conserved globular core and a divergent C-terminal tail.  The histone H3-H4 chaperone Asf1 is involved in chromatin assembly (or disassembly), histone exchange, regulation of transcription, and chromatin silencing in several organisms.  An ASF1-EGFP fusion protein localizes to the nucleus. By tandem-affinity purification/mass spectrometry as well as yeast two-hybrid analysis, we identified histones H3 and H4 as ASF1 interaction partners.   This inhibition requires Asf1 binding to H3-H4 and Rtt109 KAT activity, but not tail acetylation of H3-H4 or K56 acetylation of H3.  Asf1 is a conserved histone H3/H4 chaperone that can assemble and disassemble nucleosomes and promote histone acetylation.  Here we characterize further interactions between budding yeast (Saccharomyces cerevisiae) Asf1 and Set2 using assays of intragenic transcription, H3/H4 posttranslational modification, coding region cross-linking of Asf1 and Set2, and cooccurrence of Asf1 and Set2 in protein complexes.  Consistent with this possibility, we show that Asf1 stimulates Set2 occupancy of the coding region of a highly transcribed gene by a mechanism that depends on Asf1 binding to H3/H4.  Drosophila histones H3 and H4 can also be produced as a soluble (H3H4)(2) heterotetrameric complex if they are co-expressed with the histone chaperone Asf1. Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4. Newly synthesized histones H3-H4 first bind histone chaperone Asf1 and are then transferred to other chaperones for nucleosome assembly The C terminus of the histone chaperone Asf1 cross-links to histone H3 in yeast and promotes interaction with histones H3 and H4 Histone chaperone Asf1 is required for histone H3 lysine 56 acetylation, a modification associated with S phase in mitosis and meiosis Antisilencing function 1 (ASF1) is a major histone H3-H4 chaperone that deposits histones H3 and H4 onto DNA Rtt109, a recently discovered histone acetyltransferase (HAT) from Saccharomyces cerevisiae, functions with the histone chaperone Asf1 to acetylate lysine K56 on histone H3 (H3K56), a modification associated with newly synthesized histones In this issue of Cell, English et al. present the first crystal structure of a histone chaperone (Asf1) bound to histones (the H3/H4 heterodimer) By tandem-affinity purification/mass spectrometry as well as yeast two-hybrid analysis, we identified histones H3 and H4 as ASF1 interaction partners. Anti-silencing function 1 (Asf1) is a highly conserved chaperone of histones H3/H4 that assembles or disassembles chromatin during transcription, replication, and repair. Analysis of a panel of Asf1 mutations that modulate the ability of Asf1 to bind to histones H3/H4 demonstrates that the histone binding activity of Asf1 is required for the acetylation of Lys-9 and Lys-56 on newly synthesized H3. Thus Rad53 competes with histones H3-H4 and cochaperones HirA/CAF-I for binding to Asf1. Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4. Currently, the best-characterized chaperone-histone interaction is that between the ubiquitous chaperone Asf1 and a dimer of H3 and H4.[SEP]Relations: histone H3 acetylation has relations: bioprocess_protein with LEF1, bioprocess_protein with LEF1, bioprocess_protein with TAF5, bioprocess_protein with TAF5, bioprocess_protein with TAF12, bioprocess_protein with TAF12, bioprocess_protein with TAF10, bioprocess_protein with TAF10, bioprocess_protein with IRF4, bioprocess_protein with IRF4. Definitions: 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).. histone acetyltransferase defined as following: Class of enzymes that catalyze the acetylation of specific lysine residues of histones, proteins that organize eukaryotic DNA into chromatin. Among the proteins that exhibit histone acetyltransferase activity are various transcription factor coactivators. E.C. 2.3.1.48.. 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]. 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).. Set2 defined as following: Human SETD2 is located in the vicinity of 3p21.31 and is approximately 108 kb in length. This allele, which encodes histone-lysine N-methyltransferase SETD2 protein, may play a role in transcriptional activation and epigenetic modification of chromatin.. chromatin assembly defined as following: The assembly of DNA, histone proteins, other associated proteins, and sometimes RNA, into chromatin structure, beginning with the formation of the basic unit, the nucleosome, followed by organization of the nucleosomes into higher order structures, ultimately giving rise to a complex organization of specific domains within the nucleus. [PMID:20404130]. organisms defined as following: A living entity.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. H4 defined as following: This gene plays a role in mitogenesis and differentiation.. dimer defined as following: compound formed by the union of two radicals or two molecules of a simpler compound; a polymer formed from two molecules of a monomer.. 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.. modification defined as following: <p>Respond with exceptions, completions and modifications or revisions done before completion</p>. 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). 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..", "label": "no"}
{"original_question": "Does RNA polymerase II have RNA cleavage activity?", "id": "converted_55", "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_molfunc with enzyme binding, molfunc_molfunc with enzyme binding, molfunc_protein with YTHDC2, molfunc_protein with YTHDC2, molfunc_protein with PKN2, molfunc_protein with PKN2. RNA polymerase complex has relations: cellcomp_cellcomp with RNA-directed RNA polymerase complex, cellcomp_cellcomp with RNA-directed RNA polymerase complex. Definitions: 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).. 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).. 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.. 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 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). 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]. transcript defined as following: The initial RNA molecule produced by transcription..", "label": "yes"}
{"original_question": "Is scuba diving safe during pregnancy?", "id": "converted_56", "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: exposure_disease with Hazardous Waste, exposure_disease with Hazardous Waste, exposure_disease with Nitrogen Dioxide, exposure_disease with Nitrogen Dioxide, exposure_disease with Carbon Monoxide, exposure_disease with Carbon Monoxide, exposure_disease with Sulfur Dioxide, exposure_disease with Sulfur Dioxide, exposure_disease with Mercury, exposure_disease with Mercury. Definitions: birth defects defined as following: Malformations of organs or body parts during development in utero..", "label": "no"}
{"original_question": "Is there an association between carcinoid syndrome and mitral valve disease?", "id": "converted_57", "sentence1": "Is there an association between carcinoid syndrome and mitral valve disease?", "sentence2": "Other concomitant operations included mitral valve procedure (11%), aortic valve procedure (9%), patent foramen ovale or atrial septal defect closure (23%), cardiac metastasectomies or biopsy (4%), and simultaneous coronary artery bypass (11%).  High circulating serotonin (carcinoid syndrome) and serotoninergic drugs are known to cause valvulopathy that shares pathologic features with DMVD. Surgery included tricuspid valve replacement in all patients, pulmonary valve replacement in 3 and valvectomy in 7, mitral valve replacement in 6 and repair in 1, aortic valve replacement in 4 and repair in 2, CABG in 2, and patent foramen ovale closure in 5.  We report two observations of significant left heart involvement in patients with the carcinoid syndrome assessed by transthoracic and transoesophageal echocardiography. Echocardiographic lesions of this kind have only been reported twice. In the present cases, there was mitral involvement with mitral regurgitation in one case and a mitro-aortic involvement with mitral and aortic regurgitation in the other. An observation of carcinoid syndrome in a woman of 47 suffering from malignant carcinoid of the ileum with metastases into the liver and right ovary is described. The clinical picture included diarrhea, heat waves, bronchospasms, hypertension, hyperserotoninemia, affection of the mitral valve and left atrium.  A case of carcinoid syndrome, stemming from a tumor of the large intestine with hepatic metastases, is reported. Clinical features included cardiac disease with triple valvular lesion: tricuspid insufficiency with stenosis, pulmonary artery stenosis and mitral insufficiency.  High circulating serotonin (carcinoid syndrome) and serotoninergic drugs are known to cause valvulopathy that shares pathologic features with DMVD.[SEP]Relations: heart valve disease has relations: disease_disease with mitral valve disease, disease_disease with mitral valve disease. congenital mitral valve insufficiency has relations: disease_disease with mitral valve disease, disease_disease with mitral valve disease, disease_disease with vascular insufficiency disorder, disease_disease with vascular insufficiency disorder. carcinoid syndrome has relations: disease_disease with syndromic disease, disease_disease with syndromic disease, disease_disease with carcinoid crisis, disease_disease with carcinoid crisis. Definitions: tricuspid valve replacement defined as following: Surgery performed with the purpose of replacing a degenerated, calcified, malformed, dysfunctional, etc. tricuspid valve with bioprosthetic, homograft or autograft valve.. 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.. carcinoid syndrome defined as following: A symptom complex associated with CARCINOID TUMOR and characterized by attacks of severe flushing of the skin, diarrheal watery stools, bronchoconstriction, sudden drops in blood pressure, edema, and ascites. The carcinoid tumors are usually located in the gastrointestinal tract and metastasize to the liver. Symptoms are caused by tumor secretion of serotonin, prostaglandins, and other biologically active substances. Cardiac manifestations constitute CARCINOID HEART DISEASE. (Dorland, 27th ed; Stedman, 25th ed). tricuspid insufficiency defined as following: Backflow of blood from the RIGHT VENTRICLE into the RIGHT ATRIUM due to imperfect closure of the TRICUSPID VALVE.. valvulopathy defined as following: Pathological conditions involving any of the various HEART VALVES and the associated structures (PAPILLARY MUSCLES and CHORDAE TENDINEAE).. mitral insufficiency defined as following: Backflow of blood from the LEFT VENTRICLE into the LEFT ATRIUM due to imperfect closure of the MITRAL VALVE. This can lead to mitral valve regurgitation.. pulmonary artery stenosis defined as following: A congenital or acquired cardiovascular abnormality characterized by the narrowing of the lumen of the main pulmonary artery or its branches. Signs and symptoms include dyspnea, tachypnea, tachycardia, fatigue, and edema.. cardiac disease defined as following: Pathological conditions involving the HEART including its structural and functional abnormalities.. mitral valve defined as following: The valve between the left atrium and left ventricle of the heart.. bronchospasms defined as following: Spasmodic contraction of the smooth muscle of the bronchi.. 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.. 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.. mitral defined as following: a valve that controls blood flow between heart chambers. mitral valve disease defined as following: A heart disorder characterized by a defect in mitral valve structure or function..", "label": "yes"}
{"original_question": "Do bacteria from the genus Morexella cause respiratory infections?", "id": "converted_58", "sentence1": "Do bacteria from the genus Morexella cause respiratory infections?", "sentence2": "gainst pathogens associated with respiratory tract ailments [Staphylococcus aureus (ATCC 25923), Klebsiella pneumoniae (ATCC 13883) and Morexella cattarhalis (ATCC 14468)]  The efficacy and safety of oral ofloxacin, 400 mg once daily, for the treatment of patients with lower respiratory tract infections were studied. The most common species recovered from the sputum specimens of these patients were Haemophilus influenzae, followed by Streptococcus pneumoniae (S. pneumoniae), Staphylococcus aureus (S. aureus), Gram positive cocci unidentified, Pseudomonas aeruginosa (P. aeruginosa), Morexella catarrhalis, the efficacy and safety of oral ofloxacin 400 mg once daily for the treatment of patients with lower respiratory tract infections were studied the most common species recovered from the sputum specimens of these patients were haemophilus influenzae followed by streptococcus pneumoniae s pneumoniae staphylococcus aureus s aureus gram positive cocci unidentified pseudomonas aeruginosa p aeruginosa morexella catarrhalis streptococcus epidermidis and another haemophilus species in this order all these bacteria were susceptible to ofloxacin except for one strain of methicillin resistant s aureus a satisfactory clinical outcome was achieved in 34 of 40 patients 85 it is concluded that ofloxacin 400 mg once daily is useful for patients with respiratory tract infections.[SEP]Relations: Respiratory tract infection has relations: phenotype_phenotype with Pneumonia, phenotype_phenotype with Pneumonia, phenotype_phenotype with Acute infectious pneumonia, phenotype_phenotype with Acute infectious pneumonia, drug_effect with Deferasirox, drug_effect with Deferasirox, phenotype_phenotype with Recurrent respiratory infections, phenotype_phenotype with Recurrent respiratory infections. Ofloxacin has relations: drug_effect with Respiratory tract infection, drug_effect with Respiratory tract infection. Definitions: ofloxacin defined as following: A synthetic fluoroquinolone antibacterial agent that inhibits the supercoiling activity of bacterial DNA GYRASE, halting DNA REPLICATION.. methicillin defined as following: One of the PENICILLINS which is resistant to PENICILLINASE but susceptible to a penicillin-binding protein. It is inactivated by gastric acid so administered by injection.. S. aureus defined as following: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.. respiratory tract infections defined as following: Invasion of the host RESPIRATORY SYSTEM by microorganisms, usually leading to pathological processes or 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.. Streptococcus pneumoniae defined as following: A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals.. respiratory infections defined as following: Invasion of the host RESPIRATORY SYSTEM by microorganisms, usually leading to pathological processes or diseases..", "label": "yes"}
{"original_question": "Is Loss of function one of the cardinal signs of inflammation?", "id": "converted_59", "sentence1": "Is Loss of function one of the cardinal signs of inflammation?", "sentence2": "The concept of the four cardinal signs of acute inflammation comes from antiquity as rubor et tumor cum calore et dolore, (redness and swelling with heat and pain) extended later by functio laesa (loss of function). As early as 2000 years ago, the Roman encyclopaedist Aulus Cornelius Celsus recognised four cardinal signs of this response-redness, heat, swelling and pain; a fifth sign is loss of function.[... It was Galen who added the disturbance of function (functio laesa) as the fifth cardinal sign of inflammation to the four well-known cardinal signs of Celsus (rubor, calor, tumor, dolor). Tumor, calor, rubor, and dolor describe four cardinal signs of inflammation. The fifth-functio laesa, or loss of function-was promulgated by Rudolf Virchow, who, in the 19th century, also noted an intricate link between inflammation and cancer.[SEP]Relations: Impaired temperature sensation has relations: disease_phenotype_positive with superficial siderosis, disease_phenotype_positive with superficial siderosis, disease_phenotype_positive with pachydermoperiostosis, disease_phenotype_positive with pachydermoperiostosis, disease_phenotype_positive with Charcot-Marie-Tooth disease, disease_phenotype_positive with Charcot-Marie-Tooth disease. Portal inflammation has relations: phenotype_phenotype with Abnormality of the biliary system, phenotype_phenotype with Abnormality of the biliary system. Erythema has relations: disease_phenotype_positive with neonatal inflammatory skin and bowel disease, disease_phenotype_positive with neonatal inflammatory skin and bowel disease. Definitions: 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.. cancer defined as following: A malignant tumor at the original site of growth.. redness defined as following: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes.. swelling defined as following: Enlargement; expansion in size; sign of inflammation.", "label": "yes"}
{"original_question": "Does erythromycin increase risk of hypertrophic pyloric stenosis?", "id": "converted_60", "sentence1": "Does erythromycin increase risk of hypertrophic pyloric stenosis?", "sentence2": "Post-natal erythromycin exposure and risk of infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis. PURPOSE: Macrolide antibiotics, erythromycin, in particular, have been linked to the development of infantile hypertrophic pyloric stenosis (IHPS).  Overall, erythromycin exposure was significantly associated with development of IHPS [OR 2.45 (1.12-5.35), p\u00a0=\u00a00.02].  Data on erythromycin exposure in the first 14\u00a0days of life was extracted from 4/9 studies and identified a strong association between erythromycin exposure and subsequent development IHPS [OR 12.89 (7.67-2167), p\u00a0<\u00a00.00001].CONCLUSION: This study demonstrates a significant association between post-natal erythromycin exposure and development of IHPS, which seems stronger when exposure occurs in the first 2\u00a0weeks of life. BACKGROUND AND OBJECTIVE: Use of oral erythromycin in infants is associated with infantile hypertrophic pyloric stenosis (IHPS). CONCLUSIONS: Ingestion of oral azithromycin and erythromycin places young infants at increased risk of developing IHPS. An association between erythromycin and IHPS was also confirmed. Exposure to erythromycin in the first 14 days of life had an aOR of 13.3 (95% CI, 6.80-25.9), and 15 to 42 days of life, aOR 4.10 (95% CI, 1.69-9.91).  Early exposure to oral erythromycin in young infants, particularly in the first 2 weeks of life, has previously been associated with the development of hypertrophic pyloric stenosis. We report a case of an infant who received an abbreviated 4-day course of oral erythromycin for suspected Chlamydia conjunctivitis at 5 days of life then underwent pyloromyotomy for pyloric stenosis less than 2 weeks later. Maternal and infant use of erythromycin and other macrolide antibiotics as risk factors for infantile hypertrophic pyloric stenosis. A case report has suggested that exposure to erythromycin through breast milk might cause infantile hypertrophic pyloric stenosis. Macrolide antibiotics, erythromycin, in particular, have been linked to the development of infantile hypertrophic pyloric stenosis (IHPS). Infants prescribed systemic erythromycin had increased risk of IHPS, with the highest risk in the first 2 weeks of age (relative risk = 10.51 for erythromycin in first 2 weeks, 95% CI 4.48, 24.66). There was an association between maternal prescriptions for nonerythromycin macrolides and infantile hypertrophic pyloric stenosis (adjusted odds ratio 2.77, 95% confidence interval 1.22, 6.30, P =.01).<br><b>CONCLUSION</b>: The hypothesized association between erythromycin and infantile pyloric stenosis was not seen. Macrolide antibiotics, erythromycin, in particular, have been linked to the development of infantile hypertrophic pyloric stenosis (IHPS).[SEP]Relations: hypertrophic pyloric stenosis has relations: disease_disease with intestinal disease, disease_disease with intestinal disease, disease_disease with pyloric stenosis (disease), disease_disease with pyloric stenosis (disease), disease_disease with Mendelian disease, disease_disease with Mendelian disease, disease_disease with pyloric stenosis, infantile hypertrophic, disease_disease with pyloric stenosis, infantile hypertrophic. pyloric stenosis, infantile hypertrophic has relations: disease_phenotype_positive with Hypochloremic metabolic alkalosis, disease_phenotype_positive with Hypochloremic metabolic alkalosis. Definitions: Chlamydia conjunctivitis defined as following: An infection of the eyes characterized by the presence in conjunctival epithelial cells of inclusion bodies indistinguishable from those of trachoma. It is acquired by infants during birth and by adults from swimming pools. The etiological agent is CHLAMYDIA TRACHOMATIS whose natural habitat appears to be the genito-urinary tract. Inclusion conjunctivitis is a less severe disease than trachoma and usually clears up spontaneously.. IHPS defined as following: An abnormality characterized by thickening of the muscle in the wall of the pylorus. It results in the narrowing of the pyloric channel. The overlying mucosa may appear hypertrophic as well. Clinical signs and symptoms appear early in life and include projectile vomiting and dehydration.. hypertrophic pyloric stenosis defined as following: An abnormality characterized by thickening of the muscle in the wall of the pylorus. It results in the narrowing of the pyloric channel. The overlying mucosa may appear hypertrophic as well. Clinical signs and symptoms appear early in life and include projectile vomiting and dehydration..", "label": "yes"}
{"original_question": "Has the proteome of mice hippocampus been analysed?", "id": "converted_61", "sentence1": "Has the proteome of mice hippocampus been analysed?", "sentence2": "We employed a discovery-based proteomic approach in subcellular fractions of hippocampal tissue from chronic intermittent alcohol (CIE)-exposed C57Bl/6J mice to gain insight into alcohol-induced changes in GluN2B signaling complexes.   We employed shotgun liquid chromatography-mass spectrometry (LC-MS) proteomic and metabonomic profiling approaches on prefrontal cortex (PFC) and hippocampal (HPC) tissue from Df(16)A+/-mice, a model of the 22q11.2 deletion syndrome.   Molecular alterations in the frontal cortex and hippocampus ofTsc1+/-and control mice, with or without rapamycin treatment, were investigated. A quantitative mass spectrometry-based shotgun proteomic approach (LC-MSE) was employed as an unbiased method to detect changes in protein levels. This dataset reports on the analysis of mouse hippocampus by LC-MS/MS, from mice fed a diet that was either deficient in n-3 FA (n-3 Def) or sufficient in n-3 FA (n-3 Adq).  Using isobaric tags for relative and absolute quantitation (iTRAQ) and proteomic methods, here we identified learning-induced changes in the hippocampal proteome of non-transgenic (NonTg) and 3 \u00d7 Tg-AD mice, a widely used animal model of AD.[SEP]Relations: hippocampus fimbria has relations: anatomy_anatomy with central nervous system cell part cluster, anatomy_anatomy with central nervous system cell part cluster. frontal cortex has relations: anatomy_protein_present with HIPK3, anatomy_protein_present with HIPK3, anatomy_protein_present with HIPK4, anatomy_protein_present with HIPK4, anatomy_protein_present with HIPK2, anatomy_protein_present with HIPK2, anatomy_protein_present with HIPK1, anatomy_protein_present with HIPK1. Definitions: 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.. 22q11.2 deletion syndrome defined as following: Congenital syndrome characterized by a wide spectrum of characteristics including the absence of the THYMUS and PARATHYROID GLANDS resulting in T-cell immunodeficiency, HYPOCALCEMIA, defects in the outflow tract of the heart, and craniofacial anomalies.. hippocampal defined as following: A curved gray matter structure of the temporal lobe lying on the floor of the lateral ventricle of the brain.. Molecular defined as following: Relating to or produced by or consisting of molecules.. prefrontal cortex defined as following: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the MEDIODORSAL NUCLEUS OF THE THALAMUS. The prefrontal cortex receives afferent fibers from numerous structures of the DIENCEPHALON; MESENCEPHALON; and LIMBIC SYSTEM as well as cortical afferents of visual, auditory, and somatic origin.. frontal cortex defined as following: The grey matter, or outermost layer of the frontal lobe..", "label": "yes"}
{"original_question": "SGOT is an abbreviation for an enzyme other wise known as alanine amino transferase, yes or no?", "id": "converted_62", "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: alanine-oxomalonate transaminase activity has relations: molfunc_molfunc with transaminase activity, molfunc_molfunc with transaminase activity, molfunc_molfunc with transaminase activity, molfunc_molfunc with transaminase activity. D-alanine gamma-glutamyltransferase activity has relations: molfunc_molfunc with aminoacyltransferase activity, molfunc_molfunc with aminoacyltransferase activity. glutamate pyruvate transaminase 2 deficiency has relations: disease_protein with GPT2, disease_protein with GPT2. ornithine carbamoyltransferase complex has relations: cellcomp_cellcomp with transferase complex, cellcomp_cellcomp with transferase complex. Definitions: 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). 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.. 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.. 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.. 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.. 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]. hepatitis defined as following: INFLAMMATION of the LIVER.. 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.. 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.. 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.. 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.. 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..", "label": "no"}
{"original_question": "Are organisms in the genus Morexella associated with sepsis?", "id": "converted_63", "sentence1": "Are organisms in the genus Morexella associated with sepsis?", "sentence2": "Out of 130 culture proven cases of neonatal sepsis, gram negative bacteria were found in 71 (54.6%) cases and gram positive bacteria in 59 (45.4%) cases. Staphylococcus aureus was the most common bacteria found in 35 (26.9%) cases followed by Escherichia coli in 30 (23.1%) cases. Acinetobacter species, Staphylococcus epidermidis, Klebseila, Streptococci, Enterobacter cloacae and Morexella species were found in 17 (13.1%), 17 (13.1%), 13 (10%), 7 (5.4%), 6 (4.6%), and 5 (3.8%) cases respectively.[SEP]Relations: escherichia coli infection has relations: indication with Tobramycin, indication with Tobramycin, indication with Ampicillin, indication with Ampicillin, indication with Sulbactam, indication with Sulbactam, indication with Ofloxacin, indication with Ofloxacin, indication with Ceftriaxone, indication with Ceftriaxone. Definitions: 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.. 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.. Streptococci defined as following: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment.. organisms defined as following: A living entity..", "label": "yes"}
{"original_question": "Is Apremilast effective for Behcet\u2019s syndrome?", "id": "converted_64", "sentence1": "Is Apremilast effective for Behcet\u2019s syndrome?", "sentence2": "Apremilast is an immunomodulatory agent that works through phosphodiesterase 4 inhibition. A randomized controlled trial has shown that it is effective for the management of oral and genital ulcers and is generally well tolerated. 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: Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Beh\u00e7et's syndrome.  Apremilast, an inhibitor of phosphodiesterase-4, was effective in a phase 2, double blind, placebo-controlled study. Apremilast (Otezla(\u00ae)), an oral small molecule inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4), is under development with Celgene Corporation for the treatment of psoriatic arthritis, psoriasis, ankylosing spondylitis, Beh\u00e7et's syndrome, atopic dermatitis, and rheumatoid arthritis. There were two serious adverse events in patients receiving apremilast.<br><b>CONCLUSIONS</b>: Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Beh\u00e7et's syndrome. Apremilast (Otezla(\u00ae)), an oral small molecule inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4), is under development with Celgene Corporation for the treatment of psoriatic arthritis, psoriasis, ankylosing spondylitis, Beh\u00e7et's syndrome, atopic dermatitis, and rheumatoid arthritis. CONCLUSIONS Apremilast was effective in treating oral ulcers, which are the cardinal manifestation of Beh\u00e7et's syndrome. Apremilast, an oral small molecule inhibitor of phosphodiesterase 4 (PDE4), is in development for chronic inflammatory disorders, and has shown efficacy in psoriasis, psoriatic arthropathies, and Beh\u00e7et's syndrome. oral ulcers the hallmark of beh\u00e7et s syndrome can be resistant to conventional treatment therefore alternative agents are needed apremilast is an oral phosphodiesterase 4 inhibitor that modulates several inflammatory pathways we conducted a phase 2 multicenter placebo controlled study in which 111 patients with beh\u00e7et s syndrome who had two or more oral ulcers were randomly assigned to receive 30 mg of apremilast twice daily or placebo for 12 weeks this regimen was followed by a 12 week extension phase in which the placebo group was switched to apremilast and a 28 day post treatment observational follow up phase the patients and clinicians were unaware of the study assignments throughout the trial the primary end point was the number of oral ulcers at week 12 secondary outcomes included pain from these ulcers measured on a 100 mm visual analogue scale with higher scores indicating worse pain the number of genital ulcers overall disease activity and quality of life the mean sd number of oral ulcers per patient at week 12 was significantly lower in the apremilast group than in the placebo group 0 5 1 0 vs 2 1 2 6 p 0 001 the mean decline in pain from oral ulcers from baseline to week 12 was greater with apremilast than with placebo 44 7 24 3 mm vs 16 0 32 5 mm p 0 001 nausea vomiting and diarrhea were more common in the apremilast group with 22 9 and 12 incidents respectively among 55 patients than in the placebo group with 10 1 and 2 incidents respectively among 56 patients findings that were similar to those in previous studies of apremilast there were two serious adverse events in patients receiving apremilast apremilast was effective in treating oral ulcers which are the cardinal manifestation of beh\u00e7et s syndrome this preliminary study was neither large enough nor long enough to assess long term efficacy the effect on other manifestations of beh\u00e7et s syndrome or the risk of uncommon serious adverse events funded by celgene clinicaltrials gov number nct00866359. current trends in the management of beh\u00e7et s syndrome will be reviewed in this article biologic agents have gained increasing importance over the years in the management of beh\u00e7et s syndrome long term results of observational studies have shown that anti tumor necrosis factor agents may be effective in beh\u00e7et s syndrome patients with refractory eye involvement case series reporting about use of anti tumor necrosis factor agents in vascular and gastrointestinal involvement have also shown good results caution is required for infectious complications with these agents apremilast is an immunomodulatory agent that works through phosphodiesterase 4 inhibition a randomized controlled trial has shown that it is effective for the management of oral and genital ulcers and is generally well tolerated the outcome of beh\u00e7et s syndrome with major organ involvement has improved with more effective management strategies especially with the use of biologic agents in severe cases controlled trials are needed to guide physicians in making treatment decisions.[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.. 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.. 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.. phosphodiesterase 4 defined as following: A cyclic nucleotide phosphodiesterase subfamily that is found predominantly in inflammatory cells and may play a role in the regulation of CELL-MEDIATED IMMUNITY. The enzyme family includes over twenty different variants that occur due to multiple ALTERNATIVE SPLICING of the mRNA of at least four different genes.. PDE4 defined as following: A family of phosphodiesterases that hydrolyze cyclic AMP to form AMP. This enzyme family is the primary cyclic nucleotide phosphodiesterase expressed by immune cells.. organ 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.. psoriatic arthritis defined as following: A type of inflammatory arthritis associated with PSORIASIS, often involving the axial joints and the peripheral terminal interphalangeal joints. It is characterized by the presence of HLA-B27-associated SPONDYLARTHROPATHY, and the absence of rheumatoid factor.. 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). biologic agents defined as following: Endogenously synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS.. ulcers defined as following: A lesion on the surface of the skin or a mucous surface, produced by the sloughing of inflammatory necrotic tissue.. 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.. 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.. 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.. 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.. alemtuzumab defined as following: Any monoclonal antibody directed against the cell surface glycoprotein CD52, regardless of the antibody type (e.g., rat, mouse, humanized).. vascular defined as following: Any of the tubular vessels conveying the blood (arteries, arterioles, capillaries, venules, and veins).. Behcet\u2019s syndrome defined as following: Rare chronic inflammatory disease involving the small blood vessels. It is of unknown etiology and characterized by mucocutaneous ulceration in the mouth and genital region and uveitis with hypopyon. The neuro-ocular form may cause blindness and death. SYNOVITIS; THROMBOPHLEBITIS; gastrointestinal ulcerations; RETINAL VASCULITIS; and OPTIC ATROPHY may occur as well..", "label": "yes"}
{"original_question": "Does Enzastaurin improve survival of glioblastoma patients?", "id": "converted_65", "sentence1": "Does Enzastaurin improve survival of glioblastoma patients?", "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).  Enzastaurin (LY317615) in combination with bevacizumab for recurrent malignant gliomas is well-tolerated, with response and progression-free survival similar to bevacizumab monotherapy. So far, inhibition of angiogenesis by compounds such as bevacizumab, cediranib, enzastaurin or cilengitide as well as alternative dosing schedules of temozolomide did not prolong survival, neither at primary diagnosis nor at recurrent disease. Despite promising phase II clinical trial results and patient benefit in terms of clinical improvement and longer progression-free survival, an overall survival benefit has not been demonstrated in four randomized phase III trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin in recurrent glioblastoma. EXPERT OPINION: Enzastaurin and cediranib failed in randomized Phase III trials in recurrent glioblastoma, aflibercept in Phase II.  Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma. Grade 3 to 4 hematologic toxicities were significantly higher with lomustine (46 events) than with enzastaurin (one event; P < or = .001).<br><b>CONCLUSION</b>: Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma.<br> Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma. Enzastaurin has anti-glioma activity in patients with recurrent high-grade glioma, but does not appear to have enough single-agent activity to be useful as monotherapy. Enzastaurin (LY317615) in combination with bevacizumab for recurrent malignant gliomas is well-tolerated, with response and progression-free survival similar to bevacizumab monotherapy. CONCLUSION Enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma. glioblastomas are highly vascularized tumors and various antiangiogenic drugs have been investigated in clinical trials showing unclear results we performed a systematic review and a meta analysis to clarify and evaluate their effectiveness in glioblastoma patients we searched relevant published and unpublished randomized clinical trials analyzing antiangiogenic drugs versus chemotherapy in glioblastoma patients from january 2006 to january 2016 in medline web of science asco esmo and sno databases 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 bevacizumab did not improve overall survival twelve trials 4113 patients were analyzed for progression free survival among antiangiogenic drugs only bevacizumab demonstrated an improvement of progression free survival hr 0 63 p 0 001 both alone hr 0 60 p 0 003 or in combination to chemotherapy hr 0 63 p 0 001 both as first line treatment hr 0 70 p 0 001 or in recurrent disease hr 0 52 p 0 001 antiangiogenic drugs did not improve overall survival in glioblastoma patients either as first or second line treatment and either as single agent or in combination with chemotherapy among antiangiogenic drugs only bevacizumab improved progression free survival regardless of treatment line both as single agent or in combination with chemotherapy. glioblastoma is characterized by high expression levels of proangiogenic cytokines and microvascular proliferation highlighting the potential value of treatments targeting angiogenesis antiangiogenic treatment likely achieves a beneficial impact through multiple mechanisms of action ultimately however alternative proangiogenic signal transduction pathways are activated leading to the development of resistance even in tumors that initially respond the identification of biomarkers or imaging parameters to predict response and to herald resistance is of high priority despite promising phase ii clinical trial results and patient benefit in terms of clinical improvement and longer progression free survival an overall survival benefit has not been demonstrated in four randomized phase iii trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin in recurrent glioblastoma however future studies are warranted predictive markers may allow appropriate patient enrichment combination with chemotherapy may ultimately prove successful in improving overall survival and novel agents targeting multiple proangiogenic pathways may prove effective. this phase iii open label study compared the efficacy and safety of enzastaurin versus lomustine in patients with recurrent glioblastoma who grade 4 patients were randomly assigned 2 1 to receive 6 week cycles of enzastaurin 500 mg d 1 125 mg loading dose day 1 or lomustine 100 to 130 mg m 2 day 1 assuming a 45 improvement in progression free survival pfs 397 patients were required to provide 80 power to achieve statistical significance at a one sided level of 025 enrollment was terminated at 266 patients enzastaurin n 174 lomustine n 92 after a planned interim analysis for futility patient characteristics were balanced between arms median pfs 1 5 v 1 6 months hazard ratio hr 1 28 95 ci 0 97 to 1 70 overall survival 6 6 v 7 1 months hr 1 20 95 ci 0 88 to 1 65 and 6 month pfs rate p 13 did not differ significantly between enzastaurin and lomustine respectively stable disease occurred in 38 5 and 35 9 of patients and objective response occurred in 2 9 and 4 3 of patients respectively time to deterioration of physical and functional well being and symptoms did not differ between arms hr 1 12 p 54 four patients discontinued enzastaurin because of drug related serious adverse events aes eleven patients treated with enzastaurin died on study four because of aes one was drug related all four deaths that occurred in patients receiving lomustine were disease related grade 3 to 4 hematologic toxicities were significantly higher with lomustine 46 events than with enzastaurin one event p or 001 enzastaurin was well tolerated and had a better hematologic toxicity profile but did not have superior efficacy compared with lomustine in patients with recurrent glioblastoma. this study s primary objective was evaluation of the progression free survival rate at 6 months pfs 6 in patients with newly diagnosed glioblastoma without o 6 methylguanine dna methyltransferase mgmt promoter hypermethylation postsurgically treated with enzastaurin before and concomitantly with radiation therapy followed by enzastaurin maintenance therapy pfs 6 of at least 55 was set to be relevant compared with the data of the eortc 26981 22981 ncic ce 3 trial adult patients with a life expectancy of at least 12 weeks who were newly diagnosed with a histologically proven supratentorial glioblastoma without mgmt promoter hypermethylation were eligible patients were treated with enzastaurin prior to concomitantly with and after standard partial brain radiotherapy here we report on a multicenter open label uncontrolled phase ii study of patients with newly diagnosed glioblastoma without mgmt promoter hypermethylation treated with enzastaurin and radiation therapy within 4 study periods pfs 6 was 53 6 95 confidence interval ci 39 8 65 6 the median overall survival was 15 0 months 95 ci 11 9 17 9 for all patients 3 9 months 95 ci 0 8 9 0 for patients with biopsy 15 4 months 95 ci 10 1 17 9 for patients with partial resection and 18 9 months 95 ci 13 9 28 5 for patients with complete resection the safety profile in this study was as expected from previous trials and the therapy was well tolerated pfs 6 missed the primary planned outcome of 55 the secondary exploratory analysis according to resection status of the different subgroups of patients with biopsies partial resection and complete resection demonstrates the strong prognostic influence of resection on overall survival. we evaluated the efficacy of combination enzastaurin ly317615 and bevacizumab for recurrent malignant gliomas and explored serologic correlates we enrolled 81 patients with glioblastomas gbm n 40 and anaplastic gliomas ag n 41 patients received enzastaurin as a loading dose of 1125 mg followed by 500 or 875 mg daily for patients on non enzyme inducing or enzyme inducing antiepileptics respectively patients received bevacizumab 10 mg kg intravenously biweekly clinical evaluations were repeated every 4 weeks magnetic resonance imaging was obtained at baseline and every 8 weeks from treatment onset phosphorylated glycogen synthase kinase gsk 3 levels from peripheral blood mononuclear cells pbmcs were checked with each mri median overall survival was 7 5 and 12 4 months for glioblastomas and anaplastic glioma cohorts with median progression free survivals of 2 0 and 4 4 months respectively of gbm patients 3 40 7 5 were not evaluable while 8 37 22 had partial or complete response and 20 37 54 had stable disease for 2 months of the 39 evaluable ag patients 18 46 had an objective response and 16 41 had stable disease for 2 months the most common grade 3 toxicities were lymphopenia 15 hypophosphatemia 8 8 and thrombotic events 7 5 two 2 5 gbm patients died suddenly another death 1 3 occurred from intractable seizures phosphorylated gsk 3 levels from pbmcs did not correlate with treatment response a minimally important improvement in health related quality of life was self reported in 7 9 24 29 2 37 5 early response based on levin criteria was significantly associated with significantly longer progression free survival for glioblastomas enzastaurin ly317615 in combination with bevacizumab for recurrent malignant gliomas is well tolerated with response and progression free survival similar to bevacizumab monotherapy.[SEP]Relations: Temozolomide has relations: indication with brain glioblastoma, indication with brain glioblastoma. Enzastaurin has relations: drug_protein with CHEK2, drug_protein with CHEK2, drug_protein with AURKB, drug_protein with AURKB, drug_protein with AURKA, drug_protein with AURKA, drug_protein with CHEK1, drug_protein with CHEK1. Definitions: 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.\". death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. hypophosphatemia defined as following: A condition of an abnormally low level of PHOSPHATES in the blood.. 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.. 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.. temozolomide 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.. lomustine defined as following: An alkylating agent of value against both hematologic malignancies and solid tumors.. 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). 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.. lymphopenia defined as following: An abnormally small number of lymphocytes in the circulating blood.. 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.. 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.. 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). peripheral blood mononuclear cells defined as following: A peripheral blood cell with a single nucleus. This category includes lymphocytes and monocytes.. bevacizumab defined as following: An anti-VEGF humanized murine monoclonal antibody. It inhibits VEGF RECEPTORS and helps to prevent PATHOLOGIC ANGIOGENESIS.. hematologic defined as following: Pertaining to or related to the blood and blood-forming organs.. 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..", "label": "no"}
{"original_question": "Are the human bombesin receptors, GRPR and NMBR, frequently overexpressed G-protein-coupled-receptors by lung-cancers?", "id": "converted_66", "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. subtype 3 bombesin receptor binding has relations: molfunc_molfunc with bombesin receptor binding, molfunc_molfunc with bombesin receptor binding. Definitions: 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.. 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.. 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.. 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.. 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.. 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..", "label": "yes"}
{"original_question": "Is there any role of Dlx1 and Dlx2 transcription factors in cortical interneurons?", "id": "converted_67", "sentence1": "Is there any role of Dlx1 and Dlx2 transcription factors in cortical interneurons?", "sentence2": "The postnatal functions of the Dlx1&2 transcription factors in cortical interneurons (CINs) are unknown. Here, using conditional Dlx1, Dlx2, and Dlx1&2 knockouts (CKOs), we defined their roles in specific CINs. The CKOs had dendritic, synaptic, and survival defects, affecting even PV+ CINs. We provide evidence that DLX2 directly drives Gad1, Gad2, and Vgat expression, and show that mutants had reduced mIPSC amplitude. In addition, the mutants formed fewer GABAergic synapses on excitatory neurons and had reduced mIPSC frequency. Furthermore, Dlx1/2 CKO had hypoplastic dendrites, fewer excitatory synapses, and reduced excitatory input. We provide evidence that some of these phenotypes were due to reduced expression of GRIN2B (a subunit of the NMDA receptor), a high confidence Autism gene. Thus, Dlx1&2 coordinate key components of CIN postnatal development by promoting their excitability, inhibitory output, and survival. Furthermore, Dlx1/2 CKO had hypoplastic dendrites, fewer excitatory synapses, and reduced excitatory input.[SEP]Relations: GAD2 has relations: pathway_protein with MECP2 regulates transcription of genes involved in GABA signaling, pathway_protein with MECP2 regulates transcription of genes involved in GABA signaling, protein_protein with CPLX4, protein_protein with CPLX4, protein_protein with RHEX, protein_protein with RHEX, anatomy_protein_present with dorsolateral prefrontal cortex, anatomy_protein_present with dorsolateral prefrontal cortex. SLC32A1 has relations: anatomy_protein_present with dorsolateral prefrontal cortex, anatomy_protein_present with dorsolateral prefrontal cortex. Definitions: Dlx1 defined as following: Homeobox protein DLX-1 (255 aa, ~27 kDa) is encoded by the human DLX1 gene. This protein may be involved in the development of the brain, skull and face.. GRIN2B defined as following: This gene plays a role in both neurotransmitter binding and ion transport.. Gad1 defined as following: Glutamate decarboxylase 1 (594 aa, ~67 kDa) is encoded by the human GAD1 gene. This protein is involved in the conversion of glutamate to gamma-aminobutyric acid.. Gad2 defined as following: This gene plays a role in the conversion of glutamate to gamma-aminobutyric acid.. 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.. CIN defined as following: Squamous or glandular intraepithelial neoplasia that affects the cervical mucosal epithelium. There is no evidence of stromal invasion. According to the degree of cellular atypia and the associated architectural changes, it is classified as low or high grade.. 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)..", "label": "yes"}
{"original_question": "Does prolactinoma increase osteoporosis risk?", "id": "converted_68", "sentence1": "Does prolactinoma increase osteoporosis risk?", "sentence2": "Prolactinoma: A Massive Effect on Bone Mineral Density in a Young Patient. Osteoporosis has been noted to be an issue in postmenopausal women with prolactinomas. This case shows a similar impact on bone health in a young male resulting in low bone mineral density for age based on Z-score. This case report highlights the possible mechanisms for the bone loss in the setting of prolactinoma and the need for assessing bone health in such patients.  Hyperprolactinaemia related to prolactinoma significantly (more than functional hyperprolactiaemia) increases the risk of osteopenia, osteoporosis and bone fractures.  Prolactinomas are the most common type of functional pituitary tumor. Effective hyperprolactinemia treatment is of great importance, due to its potential deleterious effects including infertility, gonadal dysfunction and osteoporosis.  Prolactinomas cause hypogonadism, infertility, osteoporosis, and tumor mass effects, and are the most common type of neuroendocrine tumor. We present a 22-year-old man with multiple osteoporotic fractures associated with prolactinoma despite the use of teriparatide for 18 months. We emphasize and highlight the importance of hyperprolactinemia and fractures caused by high prolactin levels. OBJECTIVE: Patients with prolactinoma seem to be at high risk for osteopenia.  RESULTS: Compared to the matched controls, BMD of patients with prolactinoma or craniopharyngioma significantly decreased.  CONCLUSION: In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma. Data on osteoporotic fractures in hyperprolactinemia are limited. An increased prevalence of radiological vertebral fractures was recently observed in women with prolactin (PRL)-secreting adenoma, whereas it is unknown whether this observation may reflect a more general increased risk of fractures in this disease and whether the prevalence of fractures in males is affected by gonadal status. Prolactinoma presenting as chronic anaemia with osteoporosis: a case report. Six years later, he was evaluated and diagnosed with a prolactinoma and resultant osteoporosis. Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction. The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis.<br> <b>INTRODUCTION</b>: Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture. Univariate and multivariate regression analysis indicated that the bone loss in prolactinomas was significantly correlated to disease duration and hypogonadism.<br><b>CONCLUSION</b>: In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma. High serum prolactin levels lead to increase of the risk of osteopenia or/and osteoporosis. Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction.<br><b>CASE PRESENTATION</b>: We describe the case of a 70-year-old Caucasian man who presented with mild anaemia and tiredness. In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma. The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis. CONCLUSION In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma. Prolactinoma in old people may present insidiously with chronic anaemia and osteoporosis with or without sexual dysfunction. Hyperprolactinaemia related to prolactinoma significantly (more than functional hyperprolactiaemia) increases the risk of osteopenia, osteoporosis and bone fractures. INTRODUCTION Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture. In conclusion, men with prolactinoma have high prevalence of osteopenia and osteoporosis. Humans with prolactinoma are at risk for osteoporosis. Osteopenia and osteoporosis because of hyperprolactinaemia caused by prolactinoma may be followed by an increased risk of fracture. The relative risk for developing osteoporosis in women with prolactinoma was found to be 4.5, indicating that hyperprolactinemia in women is a major risk factor for osteoporosis.. In the premenopausal women, patients with prolactinoma or craniopharyngioma are often accompanied with osteopenia or osteoporosis, and disease duration and hypogonadism are the risk factors of bone loss in prolactinoma.[SEP]Relations: craniopharyngioma has relations: disease_phenotype_positive with Increased susceptibility to fractures, disease_phenotype_positive with Increased susceptibility to fractures. Teriparatide has relations: indication with osteoporosis, indication with osteoporosis, indication with postmenopausal osteoporosis, indication with postmenopausal osteoporosis. Osteopenia has relations: disease_phenotype_positive with prolactin producing pituitary gland tumor, disease_phenotype_positive with prolactin producing pituitary gland tumor. Prolactinoma has relations: disease_phenotype_positive with growth hormone secreting pituitary adenoma 1, disease_phenotype_positive with growth hormone secreting pituitary adenoma 1. Definitions: Prolactinomas defined as following: A pituitary adenoma which secretes PROLACTIN, leading to HYPERPROLACTINEMIA. Clinical manifestations include AMENORRHEA; GALACTORRHEA; IMPOTENCE; HEADACHE; visual disturbances; and CEREBROSPINAL FLUID RHINORRHEA.. 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).. Humans defined as following: Members of the species Homo sapiens.. bone loss defined as following: Decreased calcification or density of bone tissue.. tiredness 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.. fracture defined as following: A traumatic injury to the bone in which the continuity of the bone is broken.. Hyperprolactinaemia defined as following: Increased levels of PROLACTIN in the BLOOD, which may be associated with AMENORRHEA and GALACTORRHEA. Relatively common etiologies include PROLACTINOMA, medication effect, KIDNEY FAILURE, granulomatous diseases of the PITUITARY GLAND, and disorders which interfere with the hypothalamic inhibition of prolactin release. Ectopic (non-pituitary) production of prolactin may also occur. (From Joynt, Clinical Neurology, 1992, Ch36, pp77-8). neuroendocrine tumor 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.. 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). 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). gonadal dysfunction defined as following: Pathological processes of the OVARIES or the TESTES.. sexual dysfunction defined as following: Disturbances in sexual desire or performance.. vertebral fractures defined as following: Broken bones in the vertebral column.. 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.. infertility defined as following: Complete inability to conceive or induce conception.. prolactinoma defined as following: A pituitary adenoma which secretes PROLACTIN, leading to HYPERPROLACTINEMIA. Clinical manifestations include AMENORRHEA; GALACTORRHEA; IMPOTENCE; HEADACHE; visual disturbances; and CEREBROSPINAL FLUID RHINORRHEA..", "label": "yes"}
{"original_question": "Is pregabalin effective for sciatica?", "id": "converted_69", "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: gabapentin defined as following: A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of PARTIAL SEIZURES; NEURALGIA; and RESTLESS LEGS SYNDROME.. 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.. 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.. 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..", "label": "no"}
{"original_question": "Does MC1R palmitoylation reduce pigmentation?", "id": "converted_70", "sentence1": "Does MC1R palmitoylation reduce pigmentation?", "sentence2": "The melanocortin-1 receptor (MC1R), a G-protein-coupled receptor, has a crucial role in human and mouse pigmentation. Activation of MC1R in melanocytes by \u03b1-melanocyte-stimulating hormone (\u03b1-MSH) stimulates cAMP signalling and melanin production and enhances DNA repair after ultraviolet irradiation.  MC1R palmitoylation, primarily mediated by the protein-acyl transferase ZDHHC13, is essential for activating MC1R signalling, which triggers increased pigmentation, ultraviolet-B-induced G1-like cell cycle arrest and control of senescence and melanomagenesis in vitro and in vivo. The results highlight a central role for MC1R palmitoylation in pigmentation and protection against melanoma.[SEP]Relations: melanocyte-stimulating hormone receptor activity has relations: molfunc_protein with MC1R, molfunc_protein with MC1R, molfunc_protein with MC3R, molfunc_protein with MC3R, molfunc_protein with MC4R, molfunc_protein with MC4R. melanocyte adhesion has relations: bioprocess_protein with KIT, bioprocess_protein with KIT. type 1 melanocortin receptor binding has relations: molfunc_protein with MRAP2, molfunc_protein with MRAP2. Definitions: 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.. MC1R defined as following: Melanocyte-stimulating hormone receptor (317 aa, ~35 kDa) is encoded by the human MC1R gene. This protein plays a role in both hormone binding and melanogenesis.. melanocortin-1 receptor defined as following: A melanocortin receptor subtype found primarily in MELANOCYTES. It shows specificity for ALPHA-MSH and ADRENOCORTICOTROPIC HORMONE. Loss of function mutations of the type 1 melanocortin receptor account for the majority of red hair and fair skin recessive traits in human.. G-protein-coupled receptor defined as following: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.. human defined as following: Members of the species Homo sapiens.. melanoma defined as following: A benign or malignant, primary or metastatic neoplasm affecting the melanocytes..", "label": "no"}
{"original_question": "Is Tocilizumab effective for Giant-Cell Arteritis?", "id": "converted_71", "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-\u03b1 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-\u03b1 agents (mainly infliximab) in TAK. CONCLUSION: TCZ is effective in GCA. TNF-\u03b1 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.<br><b>CONCLUSION</b>: Tocilizumab is a promising treatment of giant cell arteritis but controlled trials are needed to confirm its efficacy.<br> <b>INTRODUCTION</b>: Treatment of giant cell arteritis is based on prolonged corticosteroid therapy but adverse side effects are common especially in the elderly.<br><b>CASE REPORTS</b>: We report three patients with giant cell vasculitis treated by tocilizumab, an interleukin-6 receptor antibody, owing to resistance or intolerance to corticosteroid therapy. Several studies have reported that tocilizumab is effective for aortitis associated with Takayasu's arteritis and giant cell arteritis. TNF-\u03b1 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. Preliminary clinical trial data suggest that abatacept and tocilizumab reduce the risk of relapse in GCA. Tocilizumab, an effective treatment for relapsing giant cell arteritis. TNF-\u03b1 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. Tocilizumab is a promising treatment of giant cell arteritis but controlled trials are needed to confirm its efficacy.[SEP]Relations: Tocilizumab has relations: indication with temporal arteritis, indication with temporal arteritis, drug_drug with Artemether, drug_drug with Artemether, drug_drug with Otelixizumab, drug_drug with Otelixizumab, drug_drug with Ceritinib, drug_drug with Ceritinib, indication with Castleman disease, indication with Castleman disease. Definitions: aortitis defined as following: Inflammation of the wall of the AORTA.. aspirin defined as following: The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5). 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.. Takayasu's arteritis defined as following: A chronic inflammatory process that affects the AORTA and its primary branches, such as the brachiocephalic artery (BRACHIOCEPHALIC TRUNK) and CAROTID ARTERIES. It results in progressive arterial stenosis, occlusion, and aneurysm formation. The pulse in the arm is hard to detect. Patients with aortitis syndrome often exhibit retinopathy.. 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.. GCA defined as following: Catalysis of the reaction: (7R)-7-(4-carboxybutanamido)cephalosporanate + H2O = (7R)-7-aminocephalosporanate + glutarate. [EC:3.5.1.93]. statins defined as following: Compounds that inhibit HYDROXYMETHYLGLUTARYL COA REDUCTASES. They have been shown to directly lower CHOLESTEROL synthesis.. TAK defined as following: Human CDK9 wild-type allele is located in the vicinity of 9q34.1 and is approximately 5 kb in length. This allele, which encodes cyclin-dependent kinase 9 protein, is involved in protein phosphorylation and the regulation of transcription.. 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.. 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.. GCs defined as following: Ceramide glucosyltransferase (394 aa, ~45 kDa) is encoded by the human UGCG gene. This protein is involved in the glycosylation of N-acylsphingosine.. 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.. pathogenic defined as following: A genetic variant that is known to directly contribute to the development of disease.. blindness defined as following: The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of EYE DISEASES; OPTIC NERVE DISEASES; OPTIC CHIASM diseases; or BRAIN DISEASES affecting the VISUAL PATHWAYS or OCCIPITAL LOBE.. angiotensin receptor blockers defined as following: Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR..", "label": "yes"}
{"original_question": "Are AAV vectors considered for the treatment of retinal dystrophies?", "id": "converted_72", "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"}
{"original_question": "Is Brucella abortus the organism that causes brucillosis known to cause spontaneous abortions in humans?", "id": "converted_73", "sentence1": "Is Brucella abortus the organism that causes brucillosis known to cause spontaneous abortions in humans?", "sentence2": ". Brucellosis is a major cause of pyrexia of unknown origin (PUO) Brucellosis is the most common bacterial zoonosis, and causes a considerable burden of disease in endemic countries. Cardiovascular involvement is the main cause of mortality due to infection with Brucella spp, quite abruptly, he developed asthenia and hypersomnia without any apparent cause or symptoms like fever, chills, or night sweats. On November 14, 2009, he suffered from pain and edema in the right testicle that coincided with pain in the abdomen. Clinical, serological, and bacteriological investigations confirmed the first case of unilateral orchitis in man in Ecuador caused by Brucella abortus biovar 1 Brucellosis is not frequent in Chile but it may present with life threatening complications like endocarditis. Human brucellosis exhibits diverse pathological manifestations that can affect almost any organ. In particular, osteoarticular complications are the most common focal manifestation of brucellosis and occur in 40-80% of patients. Brucella. Human brucellosis often makes the diagnosis difficult. The symptoms and clinical signs most commonly reported are fever, fatigue, malaise, chills, sweats headaches, myalgia, arthralgia, and weight loss. Some cases have been presented with only joint pain, lower backache, and involuntary limb movement, burning feet, or ischemic heart attacks.  Forty-five cases were collected (31 acute and 14 sub-acute). Contamination was digestive in 62%. Symptoms of patients were fever (93%), sweating (82%), arthralgia (78%) and splenomegaly (51%). Elevated erythrocyte sedimentation rate was determined in 80%, leukopenia in 49% and anaemia in 37% of cases. Blood cultures were positives in 39% of cases. The four sequenced strains were identified as Brucella melitensis biovar abortus.  It is also known to cause persistent undulant fever, endocarditis, arthritis, osteomyelitis and meningitis in humans. Brucella abortus is a Gram-negative intracellular bacterial pathogen that causes a zoonosis of worldwide occurrence, leading to undulant fever in humans and abortion in domestic animals. Brucella abortus is a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans. Brucella abortus is a facultative, intracellular zoonotic pathogen which can cause undulant fever in humans and abortions in cattle. Brucella abortus is a Gram-negative, facultative intracellular bacterium that causes brucellosis, a worldwide zoonotic disease leading to undulant fever in humans and abortion in cattle. Brucella abortus is a facultative intracellular bacterial pathogen that causes abortion in domestic animals and undulant fever in humans. Brucella abortus is a gram-negative, facultative intracellular pathogen that causes brucellosis, a chronic zoonotic disease resulting in abortion in pregnant cattle and undulant fever in humans. Brucella abortus is a bacterium which causes abortions and infertility in cattle and undulant fever in humans. Brucella abortus is the etiologic agent of bovine brucellosis and causes a chronic disease in humans known as undulant fever. No case of acute Brucella infection was demonstrated; however, there were 5 cases in which the serological finding was consistent with chronic brucellosis (4%). In all these cases no positive evidence of close animal contact could be found; furthermore of the 12,1% of women who actually handled domestic animals, only 1 had a history of previous abortion[SEP]Relations: brucellosis has relations: disease_phenotype_positive with Spontaneous abortion, disease_phenotype_positive with Spontaneous abortion, disease_disease with Brucella brucellosis, disease_disease with Brucella brucellosis, disease_disease with Brucella melitensis brucellosis, disease_disease with Brucella melitensis brucellosis, disease_disease with brucellosis, bovine, disease_disease with brucellosis, bovine. Brucella melitensis brucellosis has relations: disease_disease with brucellosis, disease_disease with brucellosis. Definitions: cattle defined as following: The domesticated cow species, Bos taurus.. 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).. splenomegaly defined as following: Enlargement of the spleen.. Brucella melitensis defined as following: A species of the genus BRUCELLA whose natural hosts are sheep and goats. Other mammals, including humans, may be infected. In general, these organisms tend to be more virulent for laboratory animals than BRUCELLA ABORTUS and may cause fatal infections.. anaemia defined as following: A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.. humans defined as following: Members of the species Homo sapiens.. meningitis defined as following: Inflammation of the coverings of the brain and/or spinal cord, which consist of the PIA MATER; ARACHNOID; and DURA MATER. Infections (viral, bacterial, and fungal) are the most common causes of this condition, but subarachnoid hemorrhage (HEMORRHAGES, SUBARACHNOID), chemical irritation (chemical MENINGITIS), granulomatous conditions, neoplastic conditions (CARCINOMATOUS MENINGITIS), and other inflammatory conditions may produce this syndrome. (From Joynt, Clinical Neurology, 1994, Ch24, p6). arthritis defined as following: Acute or chronic inflammation of JOINTS.. osteomyelitis defined as following: INFLAMMATION of the bone as a result of infection. It may be caused by a variety of infectious agents, especially pyogenic (PUS - producing) BACTERIA.. headaches 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.. undulant fever defined as following: Infection caused by bacteria of the genus BRUCELLA mainly involving the MONONUCLEAR PHAGOCYTE SYSTEM. This condition is characterized by fever, weakness, malaise, and weight loss.. malaise defined as following: A feeling of general discomfort or uneasiness, an out-of-sorts feeling.. 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.. asthenia defined as following: Clinical sign or symptom manifested as debility, or lack or loss of strength and energy.. 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.. organ 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.. abdomen defined as following: The region in the abdomen extending from the thoracic DIAPHRAGM to the plane of the superior pelvic aperture (pelvic inlet). The abdominal cavity contains the PERITONEUM and abdominal VISCERA, as well as the extraperitoneal space which includes the RETROPERITONEAL SPACE.. erythrocyte defined as following: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.. sweats defined as following: The process of exocrine secretion of the SWEAT GLANDS, including the aqueous sweat from the ECCRINE GLANDS and the complex viscous fluids of the APOCRINE GLANDS.. pyrexia defined as following: An abnormal elevation of body temperature, usually as a result of a pathologic process.. chills defined as following: The sudden sensation of being cold. It may be accompanied by SHIVERING.. abortion defined as following: The unintentional or intentional loss of a pregnancy before 22 weeks gestation.. myalgia defined as following: Painful sensation in the muscles.. bacterial zoonosis defined as following: Bacterial infections that may be transmitted between non-human animals and HUMANS.. 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.. leukopenia defined as following: A laboratory test result indicating a decreased number of white blood cells in the peripheral blood.. Brucella abortus defined as following: A disease of cattle caused by bacteria of the genus BRUCELLA leading to abortion in late pregnancy. BRUCELLA ABORTUS is the primary infective agent.. weight loss defined as following: The measured decrease in body weight over a specified period of time.. endocarditis defined as following: Inflammation of the inner lining of the heart (ENDOCARDIUM), the continuous membrane lining the four chambers and HEART VALVES. It is often caused by microorganisms including bacteria, viruses, fungi, and rickettsiae. Left untreated, endocarditis can damage heart valves and become life-threatening.. hypersomnia defined as following: A sleep disorder characterized by excessive sleepiness.. Blood cultures defined as following: Test to determine the presence of blood infection (e.g. SEPSIS; BACTEREMIA).. arthralgia defined as following: Pain in the joint.. 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.. infertility defined as following: Complete inability to conceive or induce conception.. organism defined as following: A living entity..", "label": "no"}
{"original_question": "Is Cystatin D a biomarker?", "id": "converted_74", "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"}