Respond with exceptions, completions and modifications or revisions done before completion
. adrenergic defined as following: Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters.. sudden cardiac arrest defined as following: Sudden suspension of cardiac activity that is usually due to ARRHYTHMIA, in contrast to heart attack (MYOCARDIAL INFARCTION) which occurs due to blockage. The sudden suspension of cardiac activity generally requires RESUSCITATION.. gene mutation defined as following: A change in the nucleotide sequence of the TAF1 gene.. cardiac channelopathy defined as following: A disorder that affects the myocardial ion channels, altering the electrical properties of the heart and changing the ECG and/or predisposing the subject to pro-arrhythmic events.. channelopathies defined as following: A variety of neuromuscular conditions resulting from MUTATIONS in ION CHANNELS manifesting as episodes of EPILEPSY; HEADACHE DISORDERS; and DYSKINESIAS.. ventricular tachycardias 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).. channel defined as following: An independent acquisition scheme, i.e., a route or conduit through which flows data consisting of one particular measurement using one particular parameter.. LQTS defined as following: A rare group of genetic, cardiac rhythm diseases characterized by a prolongation of the QT interval at basal electrocardiography (ECG) and by a high risk of life-threatening arrhythmias.. 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).", "label": "yes"}
{"id": "converted_297", "sentence1": "Are cyclophilins proteins that bind to prolines?", "sentence2": "Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues., a characteristic of the cyclophilin family of proteins that bind prolines and often act as cis-trans peptidyl-prolyl isomerases. , The cyclophilins are widely expressed enzymes that catalyze the interconversion of the cis and trans peptide bonds of prolines. , an immunophilin on the isomerization of critical prolines that are found in the tCHT1 sequence.[SEP]Relations: Protein S human has relations: drug_protein with PROC, drug_protein with PROC, drug_drug with Proglumetacin, drug_drug with Proglumetacin, drug_drug with Procarbazine, drug_drug with Procarbazine, drug_drug with Doxycycline, drug_drug with Doxycycline, drug_drug with Progesterone, drug_drug with Progesterone. Definitions: proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. 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.-. cis defined as following: Cytokine-inducible SH2-containing protein (258 aa, ~29 kDa) is encoded by the human CISH gene. This protein is involved in the modulation of signal transduction.. cyclophilins defined as following: A family of peptidyl-prolyl cis-trans isomerases that bind to CYCLOSPORINS and regulate the IMMUNE SYSTEM. EC 5.2.1.-.", "label": "yes"}
{"id": "converted_2617", "sentence1": "Is there a link between nuclear position and DNA repair pathway choice?", "sentence2": "Nuclear position dictates DNA repair pathway choice., We demonstrate that DSBs induced at the nuclear membrane (but not at nuclear pores or nuclear interior) fail to rapidly activate the DNA damage response (DDR) and repair by homologous recombination (HR). Real-time and superresolution imaging reveal that DNA DSBs within lamina-associated domains do not migrate to more permissive environments for HR, like the nuclear pores or the nuclear interior, but instead are repaired in situ by alternative end-joining. Our results are consistent with a model in which nuclear position dictates the choice of DNA repair pathway, thus revealing a new level of regulation in DSB repair controlled by spatial organization of DNA within the nucleus., Our results are consistent with a model in which nuclear position dictates the choice of DNA repair pathway, thus revealing a new level of regulation in DSB repair controlled by spatial organization of DNA within the nucleus., Nuclear position dictates DNA repair pathway choice., Our results are consistent with a model in which nuclear position dictates the choice of DNA repair pathway, thus revealing a new level of regulation in DSB repair controlled by spatial organization of DNA within the nucleus.[SEP]Relations: nuclear envelope has relations: cellcomp_protein with DNASE1, cellcomp_protein with DNASE1, cellcomp_protein with NRM, cellcomp_protein with NRM, cellcomp_protein with LMNA, cellcomp_protein with LMNA, cellcomp_protein with RAN, cellcomp_protein with RAN, cellcomp_protein with DST, cellcomp_protein with DST. Definitions: nuclear pores defined as following: An opening through the NUCLEAR ENVELOPE formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the CELL NUCLEUS and which, under some conditions, acts as an ion channel.. 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). nuclear membrane defined as following: The membrane system of the CELL NUCLEUS that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (NUCLEAR PORE).. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine)..", "label": "yes"}
{"id": "converted_418", "sentence1": "Is there evidence that tomato juice lowers cholesterol levels?", "sentence2": "The hypocholesterolemic effect of tomato juice has been investigated in an intervention study with rats, along with the possible inhibition effect of bioactive tomato compounds binding to the HMGCR enzyme., The molecular modelling showed that components of tomato can bind to the active site of the enzyme and compete with the ligand HMGCoA. Lycopene, from tomato juice, accumulates in the liver and can inhibit the activity of the rate-limiting enzyme of cholesterol biosynthesis, HMGCR., Juice consumption significantly improved resistance of LDL+VLDL-C to Cu(2+)-mediated oxidation (P = 0.039), HDL-C (47.3 ± 15.8 to 51.7 ± 14.8 mg/dL, P<0.001), and the ratio of total-C/HDL-C (4.25 ± 1.59 to 3.63 ± 1.16, P<0.001) at 8 wk., RESULTS: Intervention with the enriched juice had no effect on the lipid profile, and serum levels of triglycerides and cholesterol (total, LDL, and HDL) remained unchanged. , Women consuming ≥10 compared with<1.5 servings/wk of tomato-based food products had significant but clinically modest improvements in total cholesterol (TC) (5.38 vs. 5.51 mmol/L; P = 0.029), the TC:HDL cholesterol ratio (4.08 vs. 4.22; P = 0.046), and hemoglobin A1c (5.02 vs. 5.13%; P<0.001) in multivariable models. Considering clinical cutpoints, women consuming ≥10 compared with<1.5 servings/wk were 31% (95% CI = 6%, 50%), 40% (95% CI = 13%, 59%), and 66% (95% CI = 20%, 86%) less likely to have elevated TC (≥6.21 mmol/L), LDL cholesterol (≥4.14 mmol/L), and hemoglobin A1c (≥6%), respectively. , In conclusion, women consuming ≥10 compared with<1.5 servings/wk of tomato-based food products had clinically modest but significant improvements in TC, the TC:HDL cholesterol ratio, and hemoglobin A1c but not other coronary biomarkers., Tomato juice decreases LDL cholesterol levels and increases LDL resistance to oxidation., Total cholesterol concentration was reduced by 5.9 (sd 10) % (P = 0.002) and LDL cholesterol concentration by 12.9 (sd 17.0) % (P = 0.0002) with the high tomato diet compared to the low tomato diet., In conclusion, a high dietary intake of tomato products had atheroprotective effects, it significantly reduced LDL cholesterol levels, and increased LDL resistance to oxidation in healthy normocholesterolaemic adults., Total, LDL and HDL cholesterol were significantly lower in the intervention group after the intake of tomato juice, Total cholesterol concentration was reduced by 5.9 (sd 10) % (P = 0.002) and LDL cholesterol concentration by 12.9 (sd 17.0) % (P = 0.0002) with the high tomato diet compared to the low tomato diet. [SEP]Relations: Cholesterol has relations: drug_drug with Folic acid, drug_drug with Folic acid, drug_drug with Riluzole, drug_drug with Riluzole, drug_drug with Testosterone cypionate, drug_drug with Testosterone cypionate, drug_drug with Topotecan, drug_drug with Topotecan, drug_drug with Rimegepant, drug_drug with Rimegepant. Definitions: HMGCR defined as following: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (888 aa, ~97 kDa) is encoded by the human HMGCR gene. This protein is involved in cholesterol synthesis.. triglycerides defined as following: An ester formed from GLYCEROL and three fatty acid groups.. LDL defined as following: A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues.. tomato defined as following: A plant species of the family SOLANACEAE, native of South America, widely cultivated for their edible, fleshy, usually red fruit.. rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. LDL cholesterol defined as following: Cholesterol which is contained in or bound to low density lipoproteins (LDL), including CHOLESTEROL ESTERS and free cholesterol.. HDL defined as following: A class of lipoproteins of small size (4-13 nm) and dense (greater than 1.063 g/ml) particles. HDL lipoproteins, synthesized in the liver without a lipid core, accumulate cholesterol esters from peripheral tissues and transport them to the liver for re-utilization or elimination from the body (the reverse cholesterol transport). Their major protein component is APOLIPOPROTEIN A-I. HDL also shuttle APOLIPOPROTEINS C and APOLIPOPROTEINS E to and from triglyceride-rich lipoproteins during their catabolism. HDL plasma level has been inversely correlated with the risk of cardiovascular diseases.. hemoglobin A1c defined as following: Products of non-enzymatic reactions between GLUCOSE and HEMOGLOBIN A, occurring as a minor fraction of the hemoglobin components of human erythrocytes. Hemoglobin A1c is hemoglobin A with glucose covalently bound to the terminal VALINE of the beta chain. Glycated hemoglobin A is used as an index of the average blood sugar level over a lifetime of erythrocytes.. cholesterol defined as following: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.. active site defined as following: The catalytic site of an enzyme, the part of an enzyme where the actual enzymatic function is performed.. HDL cholesterol defined as following: Cholesterol which is contained in or bound to high-density lipoproteins (HDL), including CHOLESTEROL ESTERS and free cholesterol.. TC defined as following: Human CD55 wild-type allele is located in the vicinity of 1q32 and is approximately 40 kb in length. This allele, which encodes complement decay-accelerating factor protein, is involved in the modulation of complement activity..", "label": "yes"}
{"id": "converted_1228", "sentence1": "Is Rheumatoid Arthritis related to myopathy?", "sentence2": "Prevalence of risk factors for statin-induced myopathy in rheumatoid arthritis patients, we describe a patient with rheumatoid arthritis and respiratory failure associated with proximal myopathy secondary to HCQ, Occurrence of chloroquine-induced myopathy after low-dose treatment of rheumatoid arthritis for seven years, a 75 year old female with rheumatoid arthritis treated with daily doses of 250 mg of chloroquine for four years. The patient visited because of several months history of predominantly proximal progressive tetraparesis with areflexia, Myopathy and neuropathy in rheumatoid arthritis, with rheumatoid arthritis (RA) have clinical or subclinical evidence of peripheral neuropathy or myopathy, The study reveals an increased prevalence of neurogenic but not myogenic changes in patients with RA compared with controls[SEP]Relations: Rheumatoid arthritis has relations: phenotype_phenotype with Arthritis, phenotype_phenotype with Arthritis, disease_phenotype_positive with rheumatoid arthritis, disease_phenotype_positive with rheumatoid arthritis, drug_effect with Acamprosate, drug_effect with Acamprosate, disease_phenotype_positive with dystonia, disease_phenotype_positive with dystonia, phenotype_phenotype with Juvenile rheumatoid arthritis, phenotype_phenotype with Juvenile rheumatoid arthritis. Definitions: peripheral neuropathy defined as following: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.. 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.. chloroquine defined as following: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.. myopathy defined as following: Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.. low-dose defined as following: A reduced quantity of a therapeutic agent prescribed to be taken at one time or at stated intervals.. tetraparesis defined as following: Weakness of all four limbs. [HPO:probinson]. HCQ defined as following: A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p970). areflexia defined as following: A finding indicating the complete absence of neurological reflexes.. respiratory failure defined as following: The significant impairment of gas exchange within the lungs resulting in hypoxia, hypercarbia, or both, to the extent that organ tissue perfusion is severely compromised. Causes include chronic obstructive pulmonary disease, asthma, emphysema, acute respiratory distress syndrome, pneumonia, pulmonary edema, pneumothorax, and congestive heart failure. Treatment requires intubation and mechanical ventilation until the time the lungs recover sufficient function.. neuropathy defined as following: A disorder affecting the cranial nerves or the peripheral nervous system. It manifests with pain, tingling, numbness, and muscle weakness. It may be the result of physical injury, toxic substances, viral diseases, diabetes, renal failure, cancer, and drugs.. 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..", "label": "yes"}
{"id": "converted_1564", "sentence1": "Are adenylyl cyclases always transmembrane proteins?", "sentence2": "ransmembrane adenylyl cyclase, Transmembrane adenylyl cyclase (tmAC) and soluble AC (sAC) , Soluble adenylyl cyclase (sAC) is a recently recognized source of the signaling molecule cyclic AMP (cAMP) that is genetically and biochemically distinct from the classic G-protein-regulated transmembrane adenylyl cyclases (tmACs)., Soluble adenylyl cyclase , transmembrane adenylyl cyclases (tmACs), and soluble adenylyl cyclase (sAC). , Here, we showed that both transmembrane AC (tmAC) and soluble AC (sAC) are distinctly involved in the regulation of sperm motility in the ascidian Ciona intestinalis. , cAMP production in beta cells is mediated not simply by transmembrane adenylyl cyclases (TMACs), but also by sAC., In contrast to tmAC, sAC produces cAMP in various intracellular microdomains close to specific cAMP targets, e.g., in nucleus and mitochondria, soluble adenylyl cyclase (sAC, ADCY10), the ubiquitous, non-transmembrane adenylyl cyclase, was found to play a key role in neuronal survival and axon growth., Central role of soluble adenylyl cyclase[SEP]Relations: mitochondrion has relations: cellcomp_protein with ACADS, cellcomp_protein with ACADS, cellcomp_protein with ACSL1, cellcomp_protein with ACSL1, cellcomp_protein with ACADSB, cellcomp_protein with ACADSB, cellcomp_protein with CYRIB, cellcomp_protein with CYRIB, cellcomp_protein with ACACB, cellcomp_protein with ACACB. Definitions: sAC defined as following: A signaling process that delays the metaphase/anaphase transition until the spindle is correctly assembled and chromosomes are attached to the spindle. [GOC:mah]. 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). mitochondria defined as following: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed). cAMP defined as following: A chemotherapy regimen consisting of cyclophosphamide, doxorubicin, methotrexate, and procarbazine that may be used in the treatment of non-small cell lung cancer (NSCLC).. Ciona intestinalis defined as following: Vase or tube shaped TUNICATES with a cosmopolitan distribution.. adenylyl cyclases defined as following: Enzymes of the lyase class that catalyze the formation of CYCLIC AMP and pyrophosphate from ATP..", "label": "no"}
{"id": "converted_2007", "sentence1": "Is the mouse Sry gene locus free of repetitive sequences?", "sentence2": "We demonstrate that the presence of long inverted repeats (IR) flanking the mouse Sry gene leads to the formation of the Sry circular transcript in cultured cells, Circularization requires the presence of both IR. As few as 400 complementary nt are necessary for this process, The presence of the IR does not significantly stimulate intermolecular annealing and trans-splicing in vivo, We have found that in an in vitro assay, the SRY protein binds to several sites of the Sry gene and especially to a (CA)25 sequence and to a (CAG)30 repeat, The Q-rich domain of the mouse sex determining gene, Sry, is encoded by an in-frame insertion of a repetitive sequence composed of mostly CAG repeats., Inverted repeat structure of the Sry locus in mice., We performed separate amplifications of DXZ4 repetitive satellite sequences on the X chromosome, and SRY gene - testis determined factor on the Y chromosome, using nested PCR, Detailed analysis of the Sry genomic locus reveals a further difference in that the mouse Sry open reading frame lies within 2.8 kilobases of unique sequence at the center of a large inverted repeat. , Detailed analysis of the Sry genomic locus reveals a further difference in that the mouse Sry open reading frame lies within 2.8 kilobases of unique sequence at the center of a large inverted repeat., The mouse genomic Sry locus is characterized by two arms of a large inverted repeat, flanking a unique region that, between an acceptor and a donor splice site, contains a single exon encoding the Sry protein., Recombination involving the repeat region may have led to an 11-kilobase deletion, precisely excising Sry in a line of XY female mice., Repetitive element analysis revealed numerous LINE-L1 elements at regions where conservation is lost among the Sry copies., Inverted repeat structure of the Sry locus in mice.[SEP]Relations: mRNA splice site selection has relations: bioprocess_protein with SRSF6, bioprocess_protein with SRSF6, bioprocess_protein with SRSF1, bioprocess_protein with SRSF1, bioprocess_protein with SRSF9, bioprocess_protein with SRSF9, bioprocess_protein with SRSF5, bioprocess_protein with SRSF5, bioprocess_protein with SRSF10, bioprocess_protein with SRSF10. Definitions: gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. Sry gene defined as following: The primary testis-determining gene in mammalians, located on the Y CHROMOSOME. It codes for a high mobility group box transcription factor (TRANSCRIPTION FACTORS) which initiates the development of the TESTES from the embryonic GONADS.. exon defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.. cultured cells defined as following: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.. repeat defined as following: Something occurring more than once.. conservation defined as following: The maintenance of certain characteristics in an unchanged condition.. Sry defined as following: Sex-determining region Y protein (204 aa, ~24 kDa) is encoded by the human SRY gene. This protein is involved in sex determination and transcriptional regulation.. IR defined as following: A lymphoma response that cannot be distinguished between flare/pseudo-progression and true progressive disease.. region defined as following: The continents and countries situated on those continents; the UNITED STATES and each of the constituent states arranged by region; CANADA and each of its provinces; AUSTRALIA and each of its states; the major bodies of water and major islands on both hemispheres; and selected major cities.. repetitive sequence defined as following: Nucleotide sequences present in multiple copies in the genome. There are several types of repeated sequences. Interspersed (or dispersed) DNA repeats (Interspersed Repetitive Sequences) are copies of transposable elements interspersed throughout the genome. Flanking (or terminal) repeats (Terminal Repeat Sequences) are sequences that are repeated on both ends of a sequence, for example, the long terminal repeats (LTRs) on retroviruses. Direct terminal repeats are in the same direction and inverted terminal repeats are opposite to each other in direction. Tandem repeats (Tandem Repeat Sequences) are repeated copies which lie adjacent to each other. These can also be direct or inverted. The ribosomal RNA and transfer RNA genes belong to the class of middle repetitive DNA.. Y chromosome defined as following: The male sex chromosome, being the differential sex chromosome carried by half the male gametes and none of the female gametes in humans and in some other male-heterogametic species in which the homologue of the X chromosome has been retained.. X chromosome defined as following: The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.. repetitive sequences defined as following: Nucleotide sequences present in multiple copies in the genome. There are several types of repeated sequences. Interspersed (or dispersed) DNA repeats (Interspersed Repetitive Sequences) are copies of transposable elements interspersed throughout the genome. Flanking (or terminal) repeats (Terminal Repeat Sequences) are sequences that are repeated on both ends of a sequence, for example, the long terminal repeats (LTRs) on retroviruses. Direct terminal repeats are in the same direction and inverted terminal repeats are opposite to each other in direction. Tandem repeats (Tandem Repeat Sequences) are repeated copies which lie adjacent to each other. These can also be direct or inverted. The ribosomal RNA and transfer RNA genes belong to the class of middle repetitive DNA..", "label": "no"}
{"id": "converted_1294", "sentence1": "Are optogenetics tools used in the study and treatment of epilepsy?", "sentence2": "The emerging revolutionary technique of optogenetics enables manipulation of the activity of specific neuronal populations in vivo with exquisite spatiotemporal resolution using light. We used optogenetic approaches to test the role of hippocampal excitatory neurons in the lithium-pilocarpine model of acute elicited seizures in awake behaving rats., This chapter focuses on the development of optogenetics and on-demand technologies for the study of epilepsy and the control of seizures., We then turn to the use of optogenetics, including on-demand optogenetics in the study of epilepsies, which highlights the powerful potential of optogenetics for epilepsy research., Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy., Therefore, one could optogenetically activate specific or a mixed population of interneurons and dissect their selective or concerted inhibitory action on principal cells. We chose to explore a conceptually novel strategy involving simultaneous activation of mixed populations of interneurons by optogenetics and study their impact on ongoing epileptiform activity in mouse acute hippocampal slices., Our data suggest that global optogenetic activation of mixed interneuron populations is a more effective approach for development of novel therapeutic strategies for epilepsy, but the initial action potential generation in principal neurons needs to be taken in consideration., Recently, a number of experiments have explored the treatments for epilepsy with optogenetic control of neurons. Here, we discuss the possibility that an optogenetic approach could be used to control the release of gliotransmitters and improve astrocyte function such as glutamate and K(+) uptake, and thereby offer a potential strategy to investigate and treat astrocyte-related epilepsy., Optogenetic and designer receptor technologies provide unprecedented and much needed specificity, allowing for spatial, temporal and cell type-selective modulation of neuronal circuits. Using such tools, it is now possible to begin to address some of the fundamental unanswered questions in epilepsy, to dissect epileptic neuronal circuits and to develop new intervention strategies. , We then turn to the use of optogenetics, including on-demand optogenetics in the study of epilepsies, which highlights the powerful potential of optogenetics for epilepsy research., Moreover, optogenetics may be considered for developing potential treatment strategies for brain diseases, particularly for excitability disorders such as epilepsy., This chapter focuses on the development of optogenetics and on-demand technologies for the study of epilepsy and the control of seizures., How might novel technologies such as optogenetics lead to better treatments in epilepsy?, WONOEP appraisal: optogenetic tools to suppress seizures and explore the mechanisms of epileptogenesis., Finally, optogenetic tools allow rapid and reversible suppression of epileptic electroencephalography (EEG) activity upon photoactivation., Our data suggest that epileptiform activity in the hippocampus caused by impaired inhibition may be controlled by optogenetic silencing of principal neurons and potentially can be developed as an alternative treatment for epilepsy., Seizure suppression by high frequency optogenetic stimulation using in vitro and in vivo animal models of epilepsy., Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy. , We first discuss the benefits and caveats to using optogenetic approaches and recent advances in optogenetics related tools. We then turn to the use of optogenetics, including on-demand optogenetics in the study of epilepsies, which highlights the powerful potential of optogenetics for epilepsy research.[SEP]Relations: epilepsy has relations: contraindication with Edetic acid, contraindication with Edetic acid, contraindication with Olanzapine, contraindication with Olanzapine, contraindication with Ergometrine, contraindication with Ergometrine, contraindication with Atomoxetine, contraindication with Atomoxetine, contraindication with Physostigmine, contraindication with Physostigmine. Definitions: interneurons defined as following: Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions.. 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.\". neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. epilepsies 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). Optogenetic defined as following: The combination of genetic and optical methods in controlling specific events with temporal precision in targeted cells of a functioning intact biological system.. epilepsy defined as following: A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313).", "label": "yes"}
{"id": "converted_4178", "sentence1": "Do bacteria release extracellular vesicles?", "sentence2": "Bacterial extracellular vesicles (EVs) are bilayered lipid membrane structures, bearing integral proteins and able to carry diverse cargo outside the cell to distant sites., Knowledge of the structure, molecular cargo and function of bacterial extracellular vesicles (BEVs) is primarily obtained from bacteria cultured in laboratory conditions. , bacteria derived-extracellular vesicles[SEP]Relations: membrane lipid metabolic process has relations: bioprocess_protein with AGMO, bioprocess_protein with AGMO, bioprocess_bioprocess with sphingolipid metabolic process, bioprocess_bioprocess with sphingolipid metabolic process, bioprocess_protein with B4GALT4, bioprocess_protein with B4GALT4, bioprocess_bioprocess with glycolipid metabolic process, bioprocess_bioprocess with glycolipid metabolic process. Bacteremia has relations: disease_phenotype_positive with staphylococcal pneumonia, disease_phenotype_positive with staphylococcal pneumonia. Definitions: EVs defined as following: The NCI EVS is set of services and resources that address NCI's needs for controlled vocabulary. The EVS Project is a collaborative effort of the Center for Bioinformatics and the NCI Office of Communications. The NCI Thesaurus, which is a biomedical thesaurus created specifically to meet the needs of the NCI, is produced by the NCI EVS project. The NCI Thesaurus is provided under an open content license. The EVS Project also produces the NCI Metathesaurus, which is based on NLM's Unified Medical Language System Metathesaurus supplemented with additional cancer-centric vocabulary. In addition the EVS Project provides NCI with licenses for MedDRA, SNOMED, ICD-O-3, and other proprietary vocabularies.. bacterial extracellular vesicles defined as following: Small membrane vesicle (< 1 um) that buds off a prokaryotic cell plasma membrane, able to carry proteins, phospholipids, lipopolysaccharides, nucleic acids, viruses, and more. Important in intercellular communication and pathogenesis; can exist within host cells. [GOC:aa, PMID:25704309]. lipid membrane defined as following: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation.. 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.. extracellular vesicles defined as following: Any vesicle that is part of the extracellular region. [GO_REF:0000064, GOC:pm, GOC:TermGenie, PMID:24769233].", "label": "yes"}
{"id": "converted_878", "sentence1": "Is dichlorphenamide effective for periodic paralysis?", "sentence2": "BACKGROUND AND PURPOSE: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP)., In one study dichlorphenamide (DCP) vs placebo was tested in two groups of participants: 42 with hypokalemic periodic paralysis (HypoPP) and 31 with hyperkalemic periodic paralysis (HyperPP), based on clinical criteria. Thirty-four of 42 participants with hypokalemic periodic paralysis completed both treatment phases. For the 34 participants having attack rate data for both treatment phases, the mean improvement in attack rate (P = 0.02) and severity-weighted attack rate (P = 0.01) on DCP relative to placebo were statistically significant. , AUTHORS' CONCLUSIONS: The largest included study that met our inclusion criteria suggested that DCP was effective in the prevention of episodic weakness in both hypokalemic and hyperkalemic periodic paralyses., For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis. , Chronically, acetazolamide, dichlorphenamide, or potassium-sparing diuretics decrease attack frequency and severity but are of little value acutely. , In the HypoPP trial, there were 13 subjects who exhibited a preference (in terms of the end point) for either DCP or placebo, and 11 of these preferred DCP. In the PSPP trial, DCP significantly reduced attack rates relative to placebo. DCP also significantly reduced attack rates relative to placebo in the HypoPP subjects. We conclude that DCP is effective in the prevention of episodic weakness in both HypoPP and PSPP., Diclofenamid has now already been administered for 2 years. It is well tolerated and has suppressed further attacks., Three patients with Hypokalemic Periodic Paralysis (HOPP)-associated progressive interattack muscle weakness, who became unresponsive or worsened by acetazolamide, responded favorably to dichlorophenamide, a more potent carbonic anhydrase inhibitor. Dichlorophenamide in single-blind placebo-controlled trials, considerably improved functional strength in two of the patients and had a moderate but definite effect in the third., Dichlorophenamide should be considered as an alternate to acetazolamide in the treatment of patients with HOPP-associated interattack muscle weakness who have become unresponsive or worsened by acetazolamide., Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP)., For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis., BACKGROUND AND PURPOSE: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP). Whether these drugs prevent vacuolar myopathy, which is a pathogenic factor in hypoPP, is unknown. , Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP)., For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis. A second trial, comparing dichlorphenamide with acetazolamide versus placebo, is currently in progress., Despite our better understanding of the pathogenesis of these disorders, current treatments are largely empirical and the evidence in favor of specific therapy largely anecdotal. For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis.[SEP]Relations: hypokalemic periodic paralysis has relations: contraindication with Desflurane, contraindication with Desflurane. hyperkalemic periodic paralysis has relations: contraindication with Phenylephrine, contraindication with Phenylephrine, contraindication with Ammonium chloride, contraindication with Ammonium chloride, contraindication with Sodium citrate, contraindication with Sodium citrate, contraindication with Calcium chloride, contraindication with Calcium chloride. Definitions: Acetazolamide defined as following: One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337). HypoPP defined as following: An autosomal dominant familial disorder characterized by recurrent episodes of skeletal muscle weakness associated with falls in serum potassium levels. The condition usually presents in the first or second decade of life with attacks of trunk and leg paresis during sleep or shortly after awakening. Symptoms may persist for hours to days and generally are precipitated by exercise or a meal high in carbohydrates. (Adams et al., Principles of Neurology, 6th ed, p1483). Dichlorophenamide defined as following: A carbonic anhydrase inhibitor that is used in the treatment of glaucoma.. HyperPP defined as following: An autosomal dominant familial disorder which presents in infancy or childhood and is characterized by episodes of weakness associated with hyperkalemia. During attacks, muscles of the lower extremities are initially affected, followed by the lower trunk and arms. Episodes last from 15-60 minutes and typically occur after a period of rest following exercise. A defect in skeletal muscle sodium channels has been identified as the cause of this condition. Normokalemic periodic paralysis is a closely related disorder marked by a lack of alterations in potassium levels during attacks of weakness. (Adams et al., Principles of Neurology, 6th ed, p1481). carbonic anhydrase defined as following: A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of CARBON DIOXIDE from the tissues to the LUNG. EC 4.2.1.1.. Periodic defined as following: Applies to a sign, symptom, or other manifestation that recurs with a fixed time interval, i.e., the symptom-free periods are always of the same length. []. DCP defined as following: Des-gamma carboxyprothrombin (622 aa, ~70 kDa) is encoded by the human F2 gene. This protein is involved in blood coagulation. This form of prothrombin is not efficiently converted to the active enzyme thrombin because it lacks gamma-carboxyglutamyl residues. These modified glutamyl residues are absent because of either vitamin K deficiency or inhibition of vitamin K activity that, in turn, inhibits the enzyme that carboxylates these residues, vitamin K-dependent gamma-carboxylase.. paralysis defined as following: A general term most often used to describe severe or complete loss of muscle strength due to motor system disease from the level of the cerebral cortex to the muscle fiber. This term may also occasionally refer to a loss of sensory function. (From Adams et al., Principles of Neurology, 6th ed, p45). dichlorphenamide defined as following: A carbonic anhydrase inhibitor that is used in the treatment of glaucoma..", "label": "yes"}
{"id": "converted_4433", "sentence1": "Should perampanel be used for amyotrophic lateral sclerosis?", "sentence2": "RESULTS: Six participants were enrolled. All had adverse events, mostly behavioral. Two completed the trial and the other four withdrew due to adverse events. All participants reported resolution of these events after discontinuation of the drug. The trial was halted due to the large number of adverse events.DISCUSSION: The use of perampanel in this study of ALS was limited by its poor tolerability, CONCLUSIONS: Perampanel was associated with a significant decline in ALSFRS-R score and was linked to worsening of the bulbar subscore in the 8 mg group., DISCUSSION: The use of perampanel in this study of ALS was limited by its poor tolerabilit[SEP]Relations: Perampanel has relations: drug_drug with Diphemanil, drug_drug with Diphemanil, drug_drug with Propranolol, drug_drug with Propranolol, drug_drug with Eplerenone, drug_drug with Eplerenone, drug_drug with Cyclopropane, drug_drug with Cyclopropane, drug_drug with Propentofylline, drug_drug with Propentofylline. Definitions: Perampanel defined as following: An orally active, non-competitive, and selective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist, with anti-epileptic activity. Although the mechanism of action through which perampanel exerts its antiepileptic effect has not been fully elucidated, this agent antagonizes the AMPA subtype of the excitatory glutamate receptor found on postsynaptic neurons in the central nervous system (CNS). This antagonistic action prevents AMPA receptor activation by glutamate and results in the inhibition of neuronal excitation, repetitive neuronal firing, and the stabilization of hyper-excited neural membranes. Glutamate, the primary excitatory neurotransmitter in the CNS, plays an important role in various neurological disorders caused by neuronal hyperexcitation.. ALS defined as following: A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94). perampanel defined as following: An orally active, non-competitive, and selective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist, with anti-epileptic activity. Although the mechanism of action through which perampanel exerts its antiepileptic effect has not been fully elucidated, this agent antagonizes the AMPA subtype of the excitatory glutamate receptor found on postsynaptic neurons in the central nervous system (CNS). This antagonistic action prevents AMPA receptor activation by glutamate and results in the inhibition of neuronal excitation, repetitive neuronal firing, and the stabilization of hyper-excited neural membranes. Glutamate, the primary excitatory neurotransmitter in the CNS, plays an important role in various neurological disorders caused by neuronal hyperexcitation.. amyotrophic lateral sclerosis defined as following: An inherited form of amyotrophic lateral sclerosis, usually inherited in an autosomal dominant pattern, caused by mutation(s) in the SOD1 gene, encoding superoxide dismutase..", "label": "no"}
{"id": "converted_2429", "sentence1": "Is Apremilast effective for Behcet’s 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 Behçet's syndrome., Apremilast, an inhibitor of phosphodiesterase-4, was effective in a phase 2, double blind, placebo-controlled study., Apremilast (Otezla(®)), 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, Behçet's syndrome, atopic dermatitis, and rheumatoid arthritis., There were two serious adverse events in patients receiving apremilast.Include only the concept itself in the domain or value set. Do not include descendents of the concept.
. gamma-H2AX defined as following: A post-translationally modified form of variant histone H2AX where the serine residue at position 139 and/or the tyrosine residue at 142 is phosphorylated. Phosphorylation of serine-139 may be a marker for DNA damage. While phosphorylation or dephosphorylation of tyrosine-142 appears to affect the recruitment of pro-apoptotic factors or DNA repair proteins, respectively.. 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.. chemicals defined as following: A substance with a defined atomic or molecular structure that results from, or takes part in, reactions involving changes in its structure, composition, or properties.. plants defined as following: Multicellular, eukaryotic life forms of kingdom Plantae. Plants acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations. It is a non-taxonomical term most often referring to LAND PLANTS. In broad sense it includes RHODOPHYTA and GLAUCOPHYTA along with VIRIDIPLANTAE.. human defined as following: Members of the species Homo sapiens.. somatic cells defined as following: Nucleated cell which has one or more diploid sets (46 pairs) of chromosomes.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"}
{"id": "converted_3366", "sentence1": "Should Pentoxifylline be used for treatment of amyotrophic lateral sclerosis?", "sentence2": ".RESULTS: At the end of the study, after 547 days of follow-up, 103 patients (51.7%) in the pentoxifylline group and 120 (59.7%) in the placebo group were alive (unadjusted risk 1.28, p = 0.107; adjusted risk 1.43, p = 0.02). In contrast, analysis of secondary outcome functional variables did not show the same negative effect of the drug. , CONCLUSIONS: Pentoxifylline is not beneficial in ALS and should be avoided in patients treated with riluzole. , RESULTS: At the end of the study, after 547 days of follow-up, 103 patients (51.7%) in the pentoxifylline group and 120 (59.7%) in the placebo group were alive (unadjusted risk 1.28, p = 0.107; adjusted risk 1.43, p = 0.02).[SEP]Relations: Pentoxifylline has relations: drug_drug with Canrenoic acid, drug_drug with Canrenoic acid, drug_drug with Phylloquinone, drug_drug with Phylloquinone, drug_drug with Penbutolol, drug_drug with Penbutolol, drug_drug with Ampicillin, drug_drug with Ampicillin, drug_drug with Eplerenone, drug_drug with Eplerenone. Definitions: ALS defined as following: A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94). Pentoxifylline defined as following: A METHYLXANTHINE derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by stimulating cytokine production.. riluzole defined as following: A glutamate antagonist (RECEPTORS, GLUTAMATE) used as an anticonvulsant (ANTICONVULSANTS) and to prolong the survival of patients with AMYOTROPHIC LATERAL SCLEROSIS.. amyotrophic lateral sclerosis defined as following: An inherited form of amyotrophic lateral sclerosis, usually inherited in an autosomal dominant pattern, caused by mutation(s) in the SOD1 gene, encoding superoxide dismutase..", "label": "no"}
{"id": "converted_181", "sentence1": "Is the abnormal dosage of ultraconserved elements disfavored in cancer cells?", "sentence2": "Abnormal dosage of ultraconserved elements is highly disfavored in healthy cells but not cancer cells., We begin by showing that depletion for UCEs characterizes the most recent large-scale human CNV datasets and then find that even newly formed de novo CNVs, which have passed through meiosis at most once, are significantly depleted for UCEs. In striking contrast, CNVs arising specifically in cancer cells are, as a rule, not depleted for UCEs and can even become significantly enriched. This observation raises the possibility that CNVs that arise somatically and are relatively newly formed are less likely to have established a CNV profile that is depleted for UCEs. Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state. In support of this latter explanation, somatic CNVs that are not associated with disease are depleted for UCEs. Finally, we show that it is possible to observe the CNVs of induced pluripotent stem (iPS) cells become depleted of UCEs over time, suggesting that depletion may be established through selection against UCE-disrupting CNVs without the requirement for meiotic divisions., Alternatively, lack of depletion for UCEs from cancer CNVs may reflect the diseased state.[SEP]Relations: malignant giant cell tumor has relations: disease_disease with cancer, disease_disease with cancer, disease_disease with giant cell tumor, disease_disease with giant cell tumor, disease_disease with giant cell tumor of soft tissue, disease_disease with giant cell tumor of soft tissue, disease_disease with malignancy in giant cell tumor of bone, disease_disease with malignancy in giant cell tumor of bone, disease_disease with malignant giant cell tumor of soft parts, disease_disease with malignant giant cell tumor of soft parts. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. cancer cells defined as following: Cells of, or derived from, a malignant tumor.. human defined as following: Members of the species Homo sapiens.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown..", "label": "no"}
{"id": "converted_3143", "sentence1": "Velocardial facial syndrome, otherwise known as Di George syndrome is caused by a deletion in chromosome 21, yes or no?", "sentence2": "The deletion of chromosome 22q11.2 is involved in the majority of DiGeorge or velo-cardiofacial syndrome., deletions of chromosome 7q11.23 (Williams syndrome), 15q11-q13 (Angelman syndrome, Prader-Willi syndrome) and 22q11 (Di George syndrome), Submicroscopic deletions of chromosome 22q11 have been reported in a multiple anomaly syndrome variously labelled as velocardiofacial syndrome, conotruncal anomaly face syndrome, and Di George syndrome, The 22q11.2 deletion syndrome (di George syndrome) is one of the most prevalent genetic disorders., UNLABELLED\nMost of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11., Submicroscopic deletions of chromosome 22q11 have been reported in a multiple anomaly syndrome variously labelled as velocardiofacial syndrome, conotruncal anomaly face syndrome, and Di George syndrome., 22q11.2DS has several presentations including Di George's syndrome, velo-cardio-facial syndrome or Shprintzen's syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1/4000 births, de novo: 90%)., Di George syndrome due to mutation on 22q or 10q) and can also result from microdeletion or point mutation (in the Shprintzen syndrome 70% represent microdeletion and 30% point mutation at 22q11, in Rubinstein-Taybi syndrome 10% cases result from microdeletions and 90% from point mutations); 7) Population incidence of microdeletions is high (1:4000 to 1:30,000) because their etiologic mechanism is related to the common unequal crossing over; 8) Imprinting plays a role in some cases, e.g., [Microdeletion of the chromosome 22q11 in children: apropos of a series of 49 patients].Most of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11. , 22q11.2DS has several presentations including Di George's syndrome, velo-cardio-facial syndrome or Shprintzen's syndrome and it is the most frequent microdeletion syndrome in the general population (prevalence estimated at 1/4000 births, de novo: 90%). , UNLABELLED: Most of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11., Most of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11.[SEP]Relations: Williams syndrome has relations: disease_disease with syndrome caused by partial chromosomal deletion, disease_disease with syndrome caused by partial chromosomal deletion, disease_disease with partial deletion of the long arm of chromosome 7, disease_disease with partial deletion of the long arm of chromosome 7. DiGeorge syndrome has relations: disease_disease with syndrome caused by partial chromosomal deletion, disease_disease with syndrome caused by partial chromosomal deletion. Abnormality of the dentition has relations: disease_phenotype_positive with chromosome 15q24 deletion syndrome, disease_phenotype_positive with chromosome 15q24 deletion syndrome, disease_phenotype_positive with chromosome 9p deletion syndrome, disease_phenotype_positive with chromosome 9p deletion syndrome. Definitions: chromosome defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.. 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.. Rubinstein-Taybi syndrome defined as following: A chromosomal disorder characterized by MENTAL RETARDATION, broad thumbs, webbing of fingers and toes, beaked nose, short upper lip, pouting lower lip, agenesis of corpus callosum, large foramen magnum, keloid formation, pulmonary stenosis, vertebral anomalies, chest wall anomalies, sleep apnea, and megacolon. The disease has an autosomal dominant pattern of inheritance and is associated with deletions of the short arm of chromosome 16 (16p13.3).. Di George's 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.. 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.. 22q defined as following: Distal (long) arm of chromosome 22. 10q defined as following: Distal (long) arm of chromosome 10. velo-cardio-facial syndrome defined as following: Typical facies with a prominent nose and retruded mandible, cleft palate, cardiovascular defects, learning disability, retarded mental development, and short stature. Elements of this syndrome are frequently present in the Robin syndrome.. Angelman syndrome defined as following: A syndrome characterized by multiple abnormalities, MENTAL RETARDATION, and movement disorders. Present usually are skull and other abnormalities, frequent infantile spasms (SPASMS, INFANTILE); easily provoked and prolonged paroxysms of laughter (hence \"happy\"); jerky puppetlike movements (hence \"puppet\"); continuous tongue protrusion; motor retardation; ATAXIA; MUSCLE HYPOTONIA; and a peculiar facies. It is associated with maternal deletions of chromosome 15q11-13 and other genetic abnormalities. (From Am J Med Genet 1998 Dec 4;80(4):385-90; Hum Mol Genet 1999 Jan;8(1):129-35). Williams syndrome defined as following: A disorder caused by hemizygous microdeletion of about 28 genes on chromosome 7q11.23, including the ELASTIN gene. Clinical manifestations include SUPRAVALVULAR AORTIC STENOSIS; MENTAL RETARDATION; elfin facies; impaired visuospatial constructive abilities; and transient HYPERCALCEMIA in infancy. The condition affects both sexes, with onset at birth or in early infancy.. 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.. Prader-Willi syndrome defined as following: An autosomal dominant disorder caused by deletion of the proximal long arm of the paternal chromosome 15 (15q11-q13) or by inheritance of both of the pair of chromosomes 15 from the mother (UNIPARENTAL DISOMY) which are imprinted (GENETIC IMPRINTING) and hence silenced. Clinical manifestations include MENTAL RETARDATION; MUSCULAR HYPOTONIA; HYPERPHAGIA; OBESITY; short stature; HYPOGONADISM; STRABISMUS; and HYPERSOMNOLENCE. (Menkes, Textbook of Child Neurology, 5th ed, p229). chromosome 21 defined as following: A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.. Di George 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..", "label": "no"}
{"id": "converted_1489", "sentence1": "Is there any role for long noncoding RNAs in adipogenesis?", "sentence2": "Long noncoding RNAs regulate adipogenesis., Here we profiled the transcriptome of primary brown and white adipocytes, preadipocytes, and cultured adipocytes and identified 175 lncRNAs that are specifically regulated during adipogenesis. Many lncRNAs are adipose-enriched, strongly induced during adipogenesis, and bound at their promoters by key transcription factors such as peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (CEBPα). RNAi-mediated loss of function screens identified functional lncRNAs with varying impact on adipogenesis. Collectively, we have identified numerous lncRNAs that are functionally required for proper adipogenesis., Here we profiled the transcriptome of primary brown and white adipocytes, preadipocytes, and cultured adipocytes and identified 175 lncRNAs that are specifically regulated during adipogenesis. Many lncRNAs are adipose-enriched, strongly induced during adipogenesis, and bound at their promoters by key transcription factors such as peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (CEBPα). [SEP]Relations: transcription factor binding has relations: molfunc_protein with EPAS1, molfunc_protein with EPAS1, molfunc_protein with AIP, molfunc_protein with AIP, molfunc_protein with PPARA, molfunc_protein with PPARA, molfunc_protein with SRY, molfunc_protein with SRY, molfunc_protein with HMGA2, molfunc_protein with HMGA2. Definitions: promoters defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. peroxisome proliferator-activated receptor γ defined as following: TRANSCRIPTION FACTORS that are activated by ligands and heterodimerize with RETINOID X RECEPTORS and bind to peroxisome proliferator response elements in the promoter regions of target genes.. white adipocytes defined as following: Fat cells with light coloration and few MITOCHONDRIA. They contain a scant ring of CYTOPLASM surrounding a single large lipid droplet or vacuole.. transcription factors defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process..", "label": "yes"}
{"id": "converted_2424", "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: Bacteremia has relations: disease_phenotype_positive with shigellosis, disease_phenotype_positive with shigellosis, disease_phenotype_positive with melioidosis, disease_phenotype_positive with melioidosis, disease_phenotype_positive with listeriosis, disease_phenotype_positive with listeriosis. escherichia coli infection has relations: disease_phenotype_positive with Recurrent gram-negative bacterial infections, disease_phenotype_positive with Recurrent gram-negative bacterial infections, disease_disease with infectious disease, disease_disease with infectious disease. Definitions: 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.. 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.. organisms defined as following: A living entity..", "label": "yes"}
{"id": "converted_3714", "sentence1": "Is deletion at 6q24.2-26 associated with shorter survival for ovarian cancer patients?", "sentence2": "Deletion at 6q24.2-26 predicts longer survival of high-grade serous epithelial ovarian cancer patients., Standard treatments for advanced high-grade serous ovarian carcinomas (HGSOCs) show significant side-effects and provide only short-term survival benefits due to disease recurrence. Thus, identification of novel prognostic and predictive biomarkers is urgently needed. We have used 42 paraffin-embedded HGSOCs, to evaluate the utility of DNA copy number alterations, as potential predictors of clinical outcome. Copy number-based unsupervised clustering stratified HGSOCs into two clusters of different immunohistopathological features and survival outcome (HR = 0.15, 95%CI = 0.03-0.81; Padj = 0.03). We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005). The prognostic value of this deletion was validated in two independent series, one consisting of 36 HGSOCs analyzed by fluorescent in situ hybridization (P = 0.04) and another comprised of 411 HGSOCs from the Cancer Genome Atlas study (TCGA) (HR = 0.67, 95%CI = 0.48-0.93, Padj = 0.019). In addition, we confirmed the association of low expression of the genes from the region with longer survival in 799 HGSOCs (HR = 0.74, 95%CI = 0.61-0.90, log-rank P = 0.002) and 675 high-FIGO stage HGSOCs (HR = 0.76, 95%CI = 0.61-0.96, log-rank P = 0.02) available from the online tool KM-plotter. Finally, by integrating copy number, RNAseq and survival data of 296 HGSOCs from TCGA we propose a few candidate genes that can potentially explain the association. Altogether our findings indicate that the 6q24.2-26 deletion is an independent marker of favorable outcome in HGSOCs with potential clinical value as it can be analyzed by FISH on tumor sections and guide the selection of patients towards more conservative therapeutic strategies in order to reduce side-effects and improve quality of life., We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005)., OBJECTIVE\n\nWe aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients., We found that loss at 6q24.2-26 was significantly associated with the cluster of longer survival independently from other confounding factors (HR = 0.06, 95%CI = 0.01-0.43, Padj = 0.005)., OBJECTIVE\nWe aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients., OBJECTIVE: We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients., We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.[SEP]Relations: Abnormality of the dentition has relations: disease_phenotype_positive with chromosome 6pter-p24 deletion syndrome, disease_phenotype_positive with chromosome 6pter-p24 deletion syndrome, disease_phenotype_positive with chromosome 15q24 deletion syndrome, disease_phenotype_positive with chromosome 15q24 deletion syndrome, disease_phenotype_positive with chromosome 8q21.11 deletion syndrome, disease_phenotype_positive with chromosome 8q21.11 deletion syndrome, disease_phenotype_positive with 22q11.2 deletion syndrome, disease_phenotype_positive with 22q11.2 deletion syndrome, disease_phenotype_positive with chromosome 4q21 deletion syndrome, disease_phenotype_positive with chromosome 4q21 deletion syndrome. 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).. region defined as following: The continents and countries situated on those continents; the UNITED STATES and each of the constituent states arranged by region; CANADA and each of its provinces; AUSTRALIA and each of its states; the major bodies of water and major islands on both hemispheres; and selected major cities.. 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.. ovarian cancer defined as following: A primary or metastatic malignant neoplasm involving the ovary. Most primary malignant ovarian neoplasms are either carcinomas (serous, mucinous, or endometrioid adenocarcinomas) or malignant germ cell tumors. Metastatic malignant neoplasms to the ovary include carcinomas, lymphomas, and melanomas..", "label": "no"}
{"id": "converted_2205", "sentence1": "Does the Abelson-related gene (ARG) gene encode for a serine kinase?", "sentence2": "One isoform of Arg/Abl2 tyrosine kinase is nuclear and the other seven cytosolic isoforms differently modulate cell morphology, motility and the cytoskeleton., The non-receptor tyrosine kinase Abelson related gene (Arg/Abl2) regulates cell migration and morphogenesis by modulating the cytoskeleton. , The human Arg (Abl2) nonreceptor tyrosine kinase has a role in cytoskeletal rearrangements by its C-terminal F-actin- and microtubule-binding sequences. , The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts., The ARG gene encodes for a nonreceptor tyrosine kinase characterized by high homology with c-Abl in the TK, SH2, and SH3 domains. This is the first report on ARG involvement in a human malignancy., Ultraviolet-A and -B differentially modify the tyrosine-kinase profile of human keratinocytes and induce the expression of Arg+., Arg (Abelson-related gene, Abl2) was the PTK with the highest prevalence (30% of all PTKs) and UVA led to a further induction of Arg expression reaching nine-fold mRNA baseline expression at 17 h after irradiation., To investigate the expression profile of protein tyrosine kinases (PTKs) in normal human epidermal keratinocytes (NHEK) in response to UVA and UVB we employed a reversed transcriptase polymerase chain reaction (PCR) approach using degenerate primers derived from the conserved catalytic domain of PTKs. , By 3'rapid amplification of cDNA ends-polymerase chain reaction (3'RACE-PCR), a novel fusion transcript was identified between the ETV6 and the Abelson-related gene (ARG) at 1q25, resulting in a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase (PTK) domains of ARG., The non-receptor tyrosine kinase Abelson related gene (Arg/Abl2) regulates cell migration and morphogenesis by modulating the cytoskeleton., Arg (Abelson-related gene, Abl2) was the PTK with the highest prevalence (30% of all PTKs) and UVA led to a further induction of Arg expression reaching nine-fold mRNA baseline expression at 17 h after irradiation., We studied the relationship of direct karyotypes, determined at diagnosis and remission, to Abelson-related tyrosine kinase activity and the cytogenetic features of erythroid and myeloid colonies derived from remission marrow of six children with acute lymphoblastic leukemia (ALL)., ABL2/ARG (ABL-related gene) belongs to the ABL (Abelson tyrosine-protein kinase) family of tyrosine kinases, The non-receptor tyrosine kinase Abelson related gene (Arg/Abl2) regulates cell migration and morphogenesis by modulating the cytoskeleton, The ARG gene encodes for a nonreceptor tyrosine kinase characterized by high homology with c-Abl in the TK, SH2, and SH3 domains., ABL2/ARG (ABL-related gene) belongs to the ABL (Abelson tyrosine-protein kinase) family of tyrosine kinases., We report that the Abelson (Abl) and Abl-related gene (Arg) nonreceptor tyrosine kinases are required for maintenance of cortical dendrites in the mouse brain., The products of the human ARG gene and the human ABL gene characterize the Abelson family of non-receptor tyrosine protein kinases., The products of the human Arg gene and human, mouse, Drosophila, and nematode Abl genes characterize the Abelson family of nonreceptor tyrosine protein kinase., By 3'rapid amplification of cDNA ends-polymerase chain reaction (3'RACE-PCR), a novel fusion transcript was identified between the ETV6 and the Abelson-related gene (ARG) at 1q25, resulting in a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase (PTK) domains of ARG., The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts.[SEP]Relations: protein tyrosine kinase binding has relations: molfunc_protein with NEDD9, molfunc_protein with NEDD9, molfunc_protein with GRM5, molfunc_protein with GRM5, molfunc_protein with ITGB1, molfunc_protein with ITGB1, molfunc_protein with ACVR1, molfunc_protein with ACVR1, molfunc_protein with CRK, molfunc_protein with CRK. Definitions: protein tyrosine kinases defined as following: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.. chimeric protein defined as following: A protein in which the coding region of two genes have become in-frame and co-continuous. Fusion proteins can be formed by chromosomal breakage and/or recombination and also can be experimentally created using recombinant DNA techniques.. ETV6 defined as following: Human ETV6 wild-type allele is located in the vicinity of 12p13 and is approximately 246 kb in length. This allele, which encodes transcription factor ETV6 protein, is involved in the repression of transcription by RNA polymerase II. Several malignancies, particularly leukemias, are linked to chromosomal translocations of this gene.. ARG defined as following: This gene plays a role in signal transduction.. erythroid defined as following: 1) Reddish in color. 2) relating to erythrocytes or their precursors.. Abelson tyrosine-protein kinase defined as following: Abelson tyrosine-protein kinase 2 (1182 aa, ~128 kDa) is encoded by the human ABL2 gene. This protein plays a role in cell motility, apoptosis, cell adhesion, receptor endocytosis, autophagy, tyrosine phosphorylation and signal transduction.. acute lymphoblastic leukemia defined as following: A type of ALL characterized by elevated levels of B-cell lymphoblasts in the bone marrow and the blood. [NCIT:C8644]. transcripts defined as following: The initial RNA molecule produced by transcription.. c-Abl defined as following: This gene is involved in cell adhesion, differentiation, division and stress response.. 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.. Abl defined as following: An autosomal recessive disorder of lipid metabolism. It is caused by mutation of the microsomal triglyceride transfer protein that catalyzes the transport of lipids (TRIGLYCERIDES; CHOLESTEROL ESTERS; PHOSPHOLIPIDS) and is required in the secretion of BETA-LIPOPROTEINS (low density lipoproteins or LDL). Features include defective intestinal lipid absorption, very low serum cholesterol level, and near absent LDL.. 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.. nematode defined as following: class of unsegmented helminths with fundamental bilateral symmetry and secondary triradiate symmetry of the oral and esophageal structures; many species are parasites.. 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.. ALL defined as following: Leukemia with an acute onset, characterized by the presence of lymphoblasts in the bone marrow and the peripheral blood. It includes the acute B lymphoblastic leukemia and acute T lymphoblastic leukemia.. tyrosine kinase defined as following: This gene is involved in both protein phosphorylation and interferon-mediated signaling.. human defined as following: Members of the species Homo sapiens.. HLH defined as following: A rare but potentially life-threatening disorder characterized by the proliferation of histiocytes and macrophages and phagocytosis of red blood cells, white blood cells, and platelets. It may be inherited or secondary, due to infections, autoimmune disorders, or underlying malignancies. Signs and symptoms include fever, lymphadenopathy, hepatomegaly, splenomegaly, and pancytopenia.. 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.. Abelson-related gene defined as following: This gene plays a role in signal transduction.. serine kinase defined as following: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors..", "label": "no"}
{"id": "converted_2796", "sentence1": "Does vesatolimod inhibit TLR7?", "sentence2": "Vesatolimod (GS-9620) is an oral agonist of toll-like receptor 7, an activator of innate and adaptive immune responses. [SEP]Relations: Vesatolimod has relations: drug_drug with Anthrax vaccine, drug_drug with Anthrax vaccine, drug_drug with BCG vaccine, drug_drug with BCG vaccine, drug_drug with Rubella virus vaccine, drug_drug with Rubella virus vaccine, drug_drug with Typhoid Vaccine Live, drug_drug with Typhoid Vaccine Live, drug_drug with Adenovirus type 7 vaccine live, drug_drug with Adenovirus type 7 vaccine live. Definitions: toll-like receptor 7 defined as following: This gene plays a role in receptor signaling and in innate immune responses.. TLR7 defined as following: Human TLR7 wild-type allele is located in the vicinity of Xp22.3 and is approximately 22 kb in length. This allele, which encodes toll-like receptor 7 protein, plays a role in pathogen recognition and innate immunity activation in response to microbial agents..", "label": "no"}
{"id": "converted_1543", "sentence1": "Is there a mouse model for Fanconi anemia?", "sentence2": "Cyclophosphamide promotes engraftment of gene-modified cells in a mouse model of Fanconi anemia without causing cytogenetic abnormalities, We compared Cy preconditioning with fludarabine (Flu) or cytarabine (AraC) or no conditioning as a control in fanca ( -/- ) mutant mice receiving gene-modified bone marrow cells, We conclude that Cy is an effective and superior preparative regimen with respect to engraftment of lentivirus-transduced cells and functional correction in fanca ( -/- ) mice, To study whether there is a causal relationship between FA pathway defects and tumour development, we have generated a mouse model with a targeted disruption of the FA core complex gene Fancf, Fancf-deficient mouse embryonic fibroblasts displayed a phenotype typical for FA cells: they showed an aberrant response to DNA cross-linking agents as manifested by G(2) arrest, chromosomal aberrations, reduced survival, and an inability to monoubiquitinate FANCD2, Fancf homozygous mice were viable, born following a normal Mendelian distribution, and showed no growth retardation or developmental abnormalities. The gonads of Fancf mutant mice functioned abnormally, showing compromised follicle development and spermatogenesis as has been observed in other FA mouse models and in FA patients, In a cohort of Fancf-deficient mice, we observed decreased overall survival and increased tumour incidence, To provide further experimental access to the FA-M complementation group we have generated Fancm-deficient mice by deleting exon 2, FANCM deficiency caused hypogonadism in mice and hypersensitivity to cross-linking agents in mouse embryonic fibroblasts (MEFs), thus phenocopying other FA mouse models, Fancm(Delta2/Delta2) mice also showed unique features atypical for FA mice, including underrepresentation of female Fancm(Delta2/Delta2) mice and decreased overall and tumor-free survival, Fancm-deficient mice reveal unique features of Fanconi anemia complementation group M, Fancf-deficient mice are prone to develop ovarian tumours, In vivo proliferation advantage of genetically corrected hematopoietic stem cells in a mouse model of Fanconi anemia FA-D1, Using an FA mouse model with a marked hematopoietic phenotype, the FA-D1 (Brca2(Delta27/Delta27)) mice, we demonstrate that the lentivirus-mediated gene therapy of FA HSCs results in the progressive expansion of genetically corrected clones in mild-conditioned FA-D1 recipients, Consistent with these data, hematopoietic progenitors from FA recipients progressively became mitomycin C resistant and their chromosomal instability was reverted, Hematopoietic dysfunction in a mouse model for Fanconi anemia group D1, We have investigated the hematopoietic phenotype of mice with a hypomorphic mutation in the Brca2/Fancd1 gene (Brca2(Delta27/Delta27) mutation), Conventional BM competition experiments showed a marked repopulation defect in Brca2(Delta27/Delta27) hematopoietic stem cells (HSCs), compared to wild-type HSCs, Moreover, we have observed for the first time in a DNA repair disease model a very significant proliferation defect in Brca2(Delta27/Delta27) HSCs maintained in their natural physiological environment, The hematopoietic phenotype associated with the Brca2(Delta27/Delta27) mutation suggests that this FA-D1 mouse model will constitute an important tool for the development of new therapies for FA, including gene therapy, In vitro phenotypic correction of hematopoietic progenitors from Fanconi anemia group A knockout mice, In this study we characterized the hematopoietic phenotype of a Fanca knockout mouse model and corrected the main phenotypic characteristics of the bone marrow (BM) progenitors using retroviral vectors, The hematopoiesis of these animals was characterized by a modest though significant thrombocytopenia, consistent with reduced numbers of BM megakaryocyte progenitors, As observed in other FA models, the hematopoietic progenitors from Fanca(-/-) mice were highly sensitive to mitomycin C (MMC), Aiming to correct the phenotype of Fanca(-/-) progenitors, purified Lin(-)Sca-1(+) cells were transduced with retroviral vectors encoding the enhanced green fluorescent protein (EGFP) gene and human FANCA genes. Lin(-)Sca-1(+) cells from Fanca(-/-) mice were transduced with an efficiency similar to that of samples from wild-type mice. More significantly, transductions with FANCA vectors corrected both the MMC hypersensitivity as well as the impaired ex vivo expansion ability that characterized the BM progenitors of Fanca(-/-) mice, The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway., Hematopoietic dysfunction in a mouse model for Fanconi anemia group D1., Bone marrow failure in the Fanconi anemia group C mouse model after DNA damage., In vivo proliferation advantage of genetically corrected hematopoietic stem cells in a mouse model of Fanconi anemia FA-D1., Assessment of the flexed-tail mouse as a possible model for Fanconi anemia: analysis of mitomycin C-induced micronuclei., The Btbd12 knockout mouse therefore establishes a disease model for Fanconi anemia and genetically links a regulator of nuclease incision complexes to the Fanconi anemia DNA crosslink repair pathway., Cyclophosphamide promotes engraftment of gene-modified cells in a mouse model of Fanconi anemia without causing cytogenetic abnormalities., Mouse models of Fanconi anemia., Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia., This review summarizes the phenotype of each of the Fanconi anemia mouse models and highlights how genetic and interventional studies using the strains have yielded novel insight into therapeutic strategies for Fanconi anemia and into how the Fanconi anemia pathway protects against genomic instability., To study FA complementation group A using the mouse as a model system, we cloned and characterized the mouse homolog of the human FANCA cDNA., Here we describe the phenotype of the Btbd12 knockout mouse, the mouse ortholog of SLX4, which recapitulates many key features of the human genetic illness Fanconi anemia., Five of these genes have been deleted or mutated in the mouse, as well as a sixth key regulatory gene, to create mouse models of Fanconi anemia, In contrast to observations made in other Fanconi anemia (FA) mouse models, low numbers of hematopoietic colony-forming cells (CFCs) were noted in Brca2(Delta27/Delta27) mice, either young or adult, Fanconi anemia group A and C double-mutant mice: functional evidence for a multi-protein Fanconi anemia complex., In addition, mouse models are also useful for testing treatments for FA., Development and characterization of immortalized fibroblastoid cell lines from an FA(C) mouse model., These mouse models display the characteristic FA feature of cellular hypersensitivity to DNA cross-linking agents[SEP]Relations: Fanconi anemia complementation group has relations: disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_phenotype_positive with Abnormal facial shape, disease_phenotype_positive with Abnormal facial shape, disease_phenotype_positive with Abnormal facial shape, disease_phenotype_positive with Abnormal facial shape. Definitions: 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.. HSCs defined as following: Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood.. cytarabine defined as following: A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472). Flu defined as following: Human ZMYND10 wild-type allele is located in the vicinity of 3p21.3 and is approximately 6 kb in length. This allele, which encodes zinc finger MYND domain-containing protein 10, is involved in motile ciliary function. Mutations in this gene are associated with primary ciliary dyskinesia-22.. FANCM defined as following: This gene plays a role in transcriptional regulation and ubiquitination.. BM defined as following: The normal process of elimination of fecal material from the RECTUM.. CFCs defined as following: A rare genetic syndrome most often caused by BRAF gene mutations. It is characterized by a distinctive facial appearance (high forehead, short nose, and widely spaced eyes), sparse and brittle hair, skin disorders, heart malformations, mental retardation and developmental delay.. fanca defined as following: Fanconi anemia caused by mutations of the FANCA gene. FANCA gene mutations are the most common cause of Fanconi anemia. This gene provides instructions for making a protein that is involved in the Fanconi anemia (FA) pathway.. genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. hypersensitivity defined as following: Heightened emotional reactivity to environmental stimuli, including emotions of others. [PMID:23250816]. tumour defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. FANCD2 defined as following: Fanconi anemia caused by mutations of the FANCD2 gene. This gene is involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing.. Btbd12 defined as following: Human SLX4 wild-type allele is located in the vicinity of 16p13.3 and is approximately 30 kb in length. This allele, which encodes structure-specific endonuclease subunit SLX4 protein, plays a role in both the regulation of endonuclease activity and the recognition of damaged DNA. Mutation of the gene is associated with Fanconi anemia complementation group P.. MMC defined as following: An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.. spermatogenesis defined as following: The process of germ cell development in the male from the primordial germ cells, through SPERMATOGONIA; SPERMATOCYTES; SPERMATIDS; to the mature haploid SPERMATOZOA.. green fluorescent protein defined as following: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.. ovarian tumours 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.. mitomycin defined as following: A group of methylazirinopyrroloindolediones obtained from certain Streptomyces strains. They are very toxic antibiotics used as ANTINEOPLASTIC AGENTS in some solid tumors. PORFIROMYCIN and MITOMYCIN are the most useful members of the group.. Bone marrow failure defined as following: A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat. [DDD:wouwehand, HPO:probinson]. 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.. megakaryocyte defined as following: Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.. 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).. gonads defined as following: The gamete-producing glands, OVARY or TESTIS.. Fancf defined as following: Fanconi anemia caused by mutations of the FANCF gene. This gene encodes a polypeptide with homology to the prokaryotic RNA-binding protein ROM.. retroviral vectors defined as following: Any one of the recombinant retroviruses (RNA viruses) designed for gene transfer applications to deliver genetic material of interest into cells. These retroviral vectors are replication defective and have decreased immunogenicity. They are able to efficiently infect dividing cells, and the exogenous genetic material is integrated into the genome of the target cell. Thereby, the expression of the exogenous gene is stable instead of transient as in the case of adenoviral vectors.. 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.. SLX4 defined as following: Structure-specific endonuclease subunit SLX4 (1834 aa, ~200 kDa) is encoded by the human SLX4 gene. This protein is involved in the both the recognition of DNA damage and the promotion of endonuclease activity.. regulatory gene defined as following: Genes which regulate or circumscribe the activity of other genes; specifically, genes which code for PROTEINS or RNAs which have GENE EXPRESSION REGULATION functions.. Fanconi anemia defined as following: Fanconi anemia caused by mutations of the FANCA gene. FANCA gene mutations are the most common cause of Fanconi anemia. This gene provides instructions for making a protein that is involved in the Fanconi anemia (FA) pathway..", "label": "yes"}
{"id": "converted_1138", "sentence1": "Does surgery for ovarian endometriomas improve fertility?", "sentence2": "CONCLUSION: Endometriomas per se appear to be the main cause of the reduced long-term reproductive performance of the affected patients, with little or no contribution from surgery. Furthermore, endometrioma surgery seems to improve the success rates of fertility treatment., Amongst the 38 women desiring pregnancy after endometrioma surgery, 19 (50%) achieved a spontaneous pregnancy during the follow-up period. , Of 33 women who wished to conceive, 67% became pregnant, spontaneously in 59%, CONCLUSIONS: Recurrence and pregnancy rates are encouraging in that they seem comparable to the best reported results after endometrioma cystectomy. , While laparoscopic excision is known to improve fertility, recurrence can cause significant ovarian damage and adverse affects on fertility., Surgery is considered to play a role within the framework of the therapeutic options to cure infertile women with the disease even though its effectiveness is generally modest. , Randomized controlled trials showed that the excision technique is associated with a higher pregnancy rate and a lower rate of recurrence although it may determine severe injury to the ovarian reserve. , Surgical treatment is associated with a high recurrence rate and its employment for women undergoing assisted conception has recently been challenged., Laparoscopic excision of ovarian endometrioma prior to IVF does not offer any additional benefit over expectant management. , For those women subsequently attempting to conceive it was also associated with a subsequent increased spontaneous pregnancy rate in women who had documented prior sub-fertility (OR 5.21 CI 2.04-13.29)., here is insufficient evidence to favour excisional surgery over ablative surgery with respect to the chance of pregnancy after controlled ovarian stimulation and intra-uterine insemination (OR 1.40 CI 0.47-4.15) . , CONCLUSIONS: These findings suggest that in a context of more than one year infertility only related to endometriosis, it is reasonable to offer these patients a complete operative laparoscopic treatment of their lesions, which enables 65% of them to be pregnant within a 8.5 months post-surgical median time to pregnancy and spontaneously in 60%. , It was also associated with a subsequent increased rate of spontaneous pregnancy women who had documented prior sub-fertility (OR 5.21 CI 2.04-13.29). AUTHORS' CONCLUSIONS: There is some evidence that excisional surgery for endometriomata provides for a more favourable outcome than drainage and ablation, with regard to the recurrence of the endometrioma, recurrence of symptoms and subsequent spontaneous pregnancy in women who were previously subfertile. , Surgery is an option for treatment, but there is no convincing evidence that it promotes a significant improvement in fertility., In conclusion, ovarian surgery for the treatment of endometriosis reduces the ovarian outcome in IVF/ICSI cycles in women >35 years old, and might also decrease pregnancy rates. , Improvement of pain symptoms occurred in 87% of the patients and fertility rate was 45%., The long-term results, especially the fertility outcome, have been promising: 12 of 20 women (60%) achieved a term pregnancy following a laparoscopic endometrioma procedure alone. , Among this group, 115 patients (54%) conceived following surgery; of these conceptions, 109 resulted in a living child., WIDER IMPLICATIONS OF THE FINDINGS: Despite the available evidence that surgery for endometriomas does not improve the outcome of ART and may damage ovarian reserve, it seems that the majority of gynaecologists in the UK offer ovarian cystectomy to their patients., Ovarian endometriomas does not exclude fertility., Removal of endometriomas before in vitro fertilization does not improve fertility outcomes: a matched, case-control study., Conclusion(s): Laparoscopic cystectomy for endometriomas before commencing an IVF cycle does not improve fertility outcomes., Despite the available evidence that surgery for endometriomas does not improve the outcome of ART and may damage ovarian reserve, it seems that the majority of gynaecologists in the UK offer ovarian cystectomy to their patients., Furthermore, laparoscopic removal of endometriomas does not improve IVF results, but may cause a decrease of ovarian responsiveness to gonadotropins., Furthermore, endometrioma surgery seems to improve the success rates of fertility treatment., Laparoscopic cystectomy for endometriomas before commencing an IVF cycle does not improve fertility outcomes[SEP]Relations: cervix endometriosis has relations: disease_disease with cervix disease, disease_disease with cervix disease, disease_disease with endometriosis (disease), disease_disease with endometriosis (disease). endometrial endometrioid adenocarcinoma has relations: disease_disease with secretory uterine corpus endometrioid adenocarcinoma, disease_disease with secretory uterine corpus endometrioid adenocarcinoma, disease_disease with endometrioid adenocarcinoma, disease_disease with endometrioid adenocarcinoma. dermoid cyst of ovary has relations: disease_disease with ovarian cystic teratoma, disease_disease with ovarian cystic teratoma. Definitions: ovarian endometrioma defined as following: A cystic form of endometriosis affecting the ovary. It may or may not be associated with endometriosis in other areas in the pelvis.. lesions defined as following: A localized pathological or traumatic structural change, damage, deformity, or discontinuity of tissue, organ, or body part.. infertility defined as following: Complete inability to conceive or induce conception.. gonadotropins defined as following: A class of formulated therapeutic analogs of the endogenous gonadotropin that stimulates or promotes the function of the gonads. Therapeutic gonadotropins are derived from animal or recombinant sources. Gonadotropins include follicle-stimulating hormone, luteinizing hormone and chorionic gonadotropin. These agents stimulate discrete cellular components of the gonads, exerting effects in both males and females. (NCI04). endometriosis defined as following: A condition in which functional endometrial tissue is present outside the UTERUS. It is often confined to the PELVIS involving the OVARY, the ligaments, cul-de-sac, and the uterovesical peritoneum..", "label": "yes"}
{"id": "converted_4148", "sentence1": "Is the glucocorticoid receptor a transcription factor?", "sentence2": "GR and KLF4, both pioneer transcription factors,, The glucocorticoid receptor (GR) is a ligand-binding dependent transcription factor that ultimately regulates vital biological processes and inflammation response through specific gene expression control, thus representing a notable drug target to explore. , The glucocorticoid receptor (GR) is a ligand-activated transcription factor that translocates to the nucleus upon hormone stimulation and distributes between the nucleoplasm and membraneless compartments named nuclear foci.[SEP]Relations: glucocorticoid receptor activity has relations: molfunc_protein with NR3C1, molfunc_protein with NR3C1. Protein S human has relations: drug_drug with Antihemophilic factor, human recombinant, drug_drug with Antihemophilic factor, human recombinant, drug_drug with Antihemophilic factor human, drug_drug with Antihemophilic factor human, drug_drug with Platelet Activating Factor, drug_drug with Platelet Activating Factor, drug_drug with Factor IX Complex (Human), drug_drug with Factor IX Complex (Human). Definitions: drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. 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). KLF4 defined as following: Krueppel-like factor 4 (470 aa, ~50 kDa) is encoded by the human KLF4 gene. This protein regulates transcription.. 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.. nucleoplasm defined as following: That part of the nuclear content other than the chromosomes or the nucleolus. [GOC:ma, ISBN:0124325653]. glucocorticoid receptor defined as following: This gene is involved in ligand-activated transcriptional regulation and mutations in the gene are associated with glucocorticoid resistance.. GR defined as following: Glutathione reductase, mitochondrial (522 aa, ~56 kDa) is encoded by the human GSR gene. This protein plays a role in the synthesis of the sulfhydryl form of glutathione.. transcription factor defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process..", "label": "yes"}
{"id": "converted_1536", "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 µM), which conjugates bilirubin, and hepatic uptake and efflux transporters, organic anion-transporting polypeptide (OATP) 1B1 (IC50 0.57 µM), OATP1B3 (IC50 0.18 µM), and multidrug resistance-associated protein (MRP) 2 (IC50 6.2 µM), 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 µM), which conjugates bilirubin, and hepatic uptake and efflux transporters, organic anion-transporting polypeptide (OATP) 1B1 (IC50 0.57 µM), OATP1B3 (IC50 0.18 µM), and multidrug resistance-associated protein (MRP) 2 (IC50 6.2 µM), which transport bilirubin and its conjugates., In vitro OATP1B1 and OATP1B3 inhibition is associated with observations of benign clinical unconjugated hyperbilirubinemia., 3. The 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: 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.. 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.. 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.. 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.. bilirubin defined as following: A bile pigment that is a degradation product of HEME.. 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).. pitavastatin defined as following: A novel statin that induces plaque regression and elevates HDL-cholesterol levels.. 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). 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.. 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.. 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.. 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.. 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).. 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.. probe defined as following: brand name of methazole herbicide. 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.. hepatocytes defined as following: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. 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.. 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.. 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.. 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.. indinavir defined as following: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability.. amprenavir defined as following: A synthetic derivative of hydroxyethylamine sulfonamide that selectively binds to and inhibits human immunodeficiency virus (HIV) protease.. bilirubin glucuronide defined as following: water soluble conjugated bilirubin.. 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). UGT1A1 defined as following: This gene is involved in controlling serum levels of bilirubin and in glucuronidation.. 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.. 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.. 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.. SLCO1B1 gene defined as following: This gene is involved in sodium-independent uptake of numerous endogenous compounds in the liver.. human defined as following: Members of the species Homo sapiens.. conjugates defined as following: A compound formed by the union of two entities or compounds..", "label": "yes"}
{"id": "converted_278", "sentence1": "Is the tricarboxylic acid (TCA) cycle affected in inflammation?", "sentence2": "In this study, the levels of amino acids and trichloroacetic acid (TCA) cycle-related molecules in the colonic tissues and sera of patients with ulcerative colitis (UC) were profiled by gas chromatography/mass spectrometry (GC/MS), with the aim of evaluating whether the clinical state induced by UC leads to variations in the amino acid profile, Our study raises the possibility that GC/MS-based profiling of amino acids and TCA cycle-related molecules is a useful early diagnostic tool for UC., Succinate is an intermediate of the tricarboxylic acid (TCA) cycle, and plays a crucial role in adenosine triphosphate (ATP) generation in mitochondria., In plasma, most metabolites in the central metabolic pathway (glycolysis and TCA cycle) were significantly downregulated after zymosan administration, Thus, IL-1beta+TNFalpha treated astrocytes show a marked decrease in glycogen levels, a slight but not significant decrease in lactate release as well as a massive increase in both the pentose phosphate pathway and TCA cycle activities., A total of 77 and 92 metabolites were detected in serum and colon tissue, respectively, and among the metabolites the compositions of TCA cycle intermediates and amino acids changed depending on the degree of colitis, Extension of these findings identified a functional role for stretch-induced inhibition of succinate dehydrogenase (SDH) in mediating normoxic HIF1A stabilization, concomitant increases in glycolytic capacity, and improved tricarboxylic acid (TCA) cycle function, These studies reveal a surprising role for HIF1A in lung protection during ALI, where normoxic HIF1A stabilization and HIF-dependent control of alveolar-epithelial glucose metabolism function as an endogenous feedback loop to dampen lung inflammation, These results suggest a cataplerosis of the TCA cycle induced by phenobarbital, caused by the massive withdrawal of succinyl-CoA by ALAS induction, such that the TCA cycle is unable to supply the reduced cofactors to the RC, The mitochondrial respiratory chain (RC) and the tricarboxylic acid (TCA) cycle were explored in the Hmbs(-/-) mouse model. RC and TCA cycle were significantly affected in comparison to controls in mice treated with phenobarbital with decreased activities of RC complexes, Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. , Enhanced mitochondrial glucose oxidation was achieved by increased recruitment of the NOTCH1 intracellular domain (NICD1) to nuclear and mitochondrial genes that encode respiratory chain components and by NOTCH-dependent induction of pyruvate dehydrogenase phosphatase 1 (Pdp1) expression, pyruvate dehydrogenase activity, and glucose flux to the TCA cycle. , Metabolic reprogramming is implicated in macrophage activation,, BHB blocks the NLRP3 inflammasome without undergoing oxidation in the TCA cycle, and independently of uncoupling protein-2 (UCP2), sirtuin-2 (SIRT2), the G protein-coupled receptor GPR109A or hydrocaboxylic acid receptor 2 (HCAR2). , Our findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of the NLRP3 inflammasome., Succinate: a metabolic signal in inflammation.[SEP]Relations: acute tricyclic antidepressant poisoning has relations: disease_disease with poisoning, disease_disease with poisoning. ulcerative colitis (disease) has relations: contraindication with Trihexyphenidyl, contraindication with Trihexyphenidyl, disease_protein with HNF4A, disease_protein with HNF4A, disease_protein with HERC2, disease_protein with HERC2. Phenobarbital has relations: drug_drug with Tricaine, drug_drug with Tricaine. Definitions: pentose defined as following: Monosaccharide sugar molecules that contain a five carbon backbone.. AAH defined as following: Aspartyl/asparaginyl beta-hydroxylase (758 aa, ~86 kDa) is encoded by the human ASPH gene. This protein is involved in amino acid hydroxylation.. 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.. mitochondria defined as following: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed). uncoupling protein-2 defined as following: A mitochondrial uncoupling protein that is expressed in many tissues and exhibits the greatest expression in SKELETAL MUSCLE. It regulates mitochondrial ATP production and the generation of REACTIVE OXYGEN SPECIES.. trichloroacetic acid defined as following: A strong acid used as a protein precipitant in clinical chemistry and also as a caustic for removing warts.. Succinate defined as following: Derivatives of SUCCINIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a 1,4-carboxy terminated aliphatic structure.. SIRT2 defined as following: A sirtuin family member found primarily in the CYTOPLASM. It is a multifunctional enzyme that contains a NAD-dependent deacetylase activity that is specific for HISTONES and a mono-ADP-ribosyltransferase activity.. pyruvate dehydrogenase phosphatase 1 defined as following: (Pyruvate dehydrogenase (lipoamide))-phosphate phosphohydrolase. A mitochondrial enzyme that catalyzes the hydrolytic removal of a phosphate on a specific seryl hydroxyl group of pyruvate dehydrogenase, reactivating the enzyme complex. EC 3.1.3.43.. succinate dehydrogenase defined as following: A flavoprotein containing oxidoreductase that catalyzes the dehydrogenation of SUCCINATE to fumarate. In most eukaryotic organisms this enzyme is a component of mitochondrial electron transport complex II.. UC defined as following: Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.. HIF1A defined as following: Hypoxia-inducible factor 1-alpha (826 aa, ~93 kDa) is encoded by the human HIF1A gene. This protein plays a role in transcriptional regulation in response to hypoxia.. adenosine triphosphate defined as following: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.. ALAS defined as following: Human ALAS1 wild-type allele is located in the vicinity of 3p21.1 and is approximately 16 kb in length. This allele, which encodes 5-aminolevulinate synthase, nonspecific, mitochondrial protein, is involved in both heme biosynthesis and lipid metabolism.. cofactors defined as following: Something that must join with another to produce a given result.. tricarboxylic acid defined as following: Organic compounds that are acyclic and contain three acid groups. A member of this class is citric acid which is the first product formed by reaction of pyruvate and oxaloacetate. (From Lehninger, Principles of Biochemistry, 1982, p443). phenobarbital defined as following: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.. astrocytes defined as following: A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from \"star\" cells) are irregularly shaped with many long processes, including those with \"end feet\" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and \"reactive astrocytes\" (along with MICROGLIA) respond to injury.. 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]. 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.. metabolites defined as following: Any substance involved in metabolism, either as a product of metabolism or as necessary for metabolism..", "label": "yes"}
{"id": "converted_1493", "sentence1": "Was modafinil tested for schizophrenia treatment?", "sentence2": "Modafinil improves antipsychotic-induced parkinsonism but not excessive daytime sleepiness, psychiatric symptoms or cognition in schizophrenia and schizoaffective disorder: a randomized, double-blind, placebo-controlled study., CONCLUSION: The data suggest that modafinil was a safe adjunctive treatment which improved parkinsonian symptoms and signs in patients with schizophrenia or schizoaffective disorder. , A review of its effects in schizophrenia suggests that modafinil facilitates cognitive functions, with pro-mnemonic effects and problem solving improvements. Emotional processing also appears to be enhanced by the drug, although to date there are only a limited number of studies., BACKGROUND: Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions. , A review of modafinil and armodafinil as add-on therapy in antipsychotic-treated patients with schizophrenia., It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain., Evidence for the use of modafinil or armodafinil as add-on therapy to antipsychotic drugs to alleviate fatigue, sleepiness and inactivity is inconclusive. One cohort study and one out of two single-dose crossover RCTs in which modafinil addition was studied could demonstrate a positive effect. All five RCTs of modafinil (three RCTs) and armodafinil (two RCTs) addition with a longer study duration could not demonstrate a positive effect. , In RCTs with a treatment duration of 4 weeks or more, however, no positive effect could be demonstrated on cognitive functioning with modafinil and armodafinil addition. Yet, four single-dose crossover RCTs of modafinil addition show significant positive effects on executive functioning, verbal memory span, visual memory, working memory, spatial planning, slowing in latency, impulse control and recognition of faces expressing sadness and sadness misattribution in the context of disgust recognition. The addition of modafinil or armodafinil to an antipsychotic regime, despite theoretical and preclinical considerations, has not been proved to enhance cognitive function, attenuate fatigue, enhance activity, improve negative symptoms and reduce weight in patients with schizophrenia., RATIONAL: In recent years, evidence suggests that modafinil may be useful for certain symptom domains of schizophrenia, especially for the negative and cognitive symptoms. , CONCLUSION: The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms. , Modafinil is a wake-promoting drug that has been shown to improve attention, memory and executive function in the healthy population and in patients with schizophrenia., CONCLUSIONS: Results of this pilot trial do not support routine use of modafinil to counteract increased weight and metabolic diseases in patients taking clozapine., Modafinil (2-((diphenylmethyl)sulfinyl)acetamide) is described as an atypical stimulant and is a putative cognition enhancer for schizophrenia, but the precise mechanisms of action remain unclear., Modafinil is a wake-promoting drug that has been shown to improve emotion discrimination in healthy individuals and attention and executive function in schizophrenia. , CONCLUSIONS: These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction., Modafinil improves working memory in healthy subjects and individuals diagnosed with schizophrenia and Attention Deficit/Hyperactivity Disorder, though the effects of modafinil have not been evaluated on working memory in methamphetamine-dependent subjects., Modafinil is a psychostimulant approved for treating excessive sleepiness in adults; off-label uses (e.g., treatment of cognitive impairment in schizophrenia, ADHD and age-related dementias) are currently being explored. , CONCLUSIONS: Results of this pilot trial do not support routine use of modafinil to treat negative symptoms, cognitive deficits, or wakefulness/fatigue in patients on clozapine., We have previously shown that the amount of movement exhibited by patients with schizophrenia is positively correlated with the volume of left anterior cingulate cortex and that this quantity of movement can be increased by modafinil. , OBJECTIVE: Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability. , RESULTS: One of 4 reviewed studies found a significant effect of modafinil as an alerting agent for antipsychotic-induced fatigue and sedation. Neither of 2 reviewed studies found modafinil to improve negative symptoms of schizophrenia. Three of 6 reviewed studies showed that modafinil may improve short-term memory, attention, and the ability to shift mental sets. , CONCLUSIONS: While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia. , Hence, before prescribing modafinil to a schizophrenia patient, the possible risks and benefits of each particular case should be evaluated., Modafinil had a substantial placebo effect on outcomes such as fatigue, excessive sleepiness and depression in patients with traumatic brain injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple sclerosis; however, it did not provide any benefit greater than placebo., RATIONALE: The wake-promoting agent modafinil selectively improves neuropsychological task performance in healthy volunteers, in adults with attention deficit hyperactivity disorder (ADHD) and in schizophrenia. , Recently, however, modafinil has been shown to improve attentional set-shifting performance in patients with schizophrenia., In addition, modafinil shows initial promise for a variety of off-label indications in psychiatry, including treatment-resistant depression, attention-deficit/hyperactivity disorder, and schizophrenia., There is increasing interest in the use of modafinil to improve cognition in schizophrenia as well as in other disorders such as attention-deficit/hyperactivity disorder., Initial findings indicate that modafinil may lead to better executive functioning and attentional performance in patients with schizophrenia. , CONCLUSIONS: Although no effect on negative symptoms was found, adjunctive therapy with modafinil may result in global improvements in patients with schizophrenia who have prominent negative symptoms., CONCLUSIONS: Modafinil did not improve cognitive control in all schizophrenia patients., . These data suggest that modafinil increases quantifiable motor behaviour in schizophrenia and may have an impact on avolition., One patient was on treatment with both modafinil and trazodone and reported no change after tapering each in separate discontinuation trials, while another 3 patients were taking sleeping medications and also noted no change after discontinuation., Neuroprotective agents as add-on therapies (e.g., modafinil, erythropoietin, glycine, D-serine, memantine and celecoxib) are currently being evaluated in schizophrenia and related disorders. , In the modafinil (N = 10) and placebo (N = 10) groups, fatigue improved significantly over time (p < .01), but there were no differences between groups on changes in fatigue, positive and negative symptoms, or cognition. , CONCLUSIONS: Modafinil modulates anterior cingulate cortex function in chronic schizophrenia but its beneficial cognitive effects may be restricted to a subset of patients requiring further characterisation., Modafinil significantly improved overall clinical condition, with 64% and 82% of patients rated as clinically improved at week 4 by a blinded clinician and the investigator respectively., Modafinil significantly improved fatigue (P = 0.025, week 3) and tended to improve cognitive functioning scores. , Although preliminary, these results suggest modafinil may be an effective and well-tolerated adjunct treatment that improves global functioning and clinical condition, and reduces fatigue in patients with schizophrenia or schizoaffective disorder. , Modafinil had some cognitive enhancing properties in schizophrenia similar to those observed in healthy adults and adult patients with ADHD. , Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia, particularly because of its beneficial effects on attentional set shifting., While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia., Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability., The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms., It has been suggested that modafinil and its isomer armodafinil as an add-on strategy to antipsychotic treatment in patients with schizophrenia may improve cognitive functioning, attenuate fatigue, inactiveness and other negative functions as well as weight gain., CONCLUSION: The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms., OBJECTIVE: Given recent reports about the off-label use of modafinil as an adjuvant for the treatment of antipsychotic-associated sedation in schizophrenia patients and the recent interest in its putative cognitive-enhancing effects in this population, we present a systematic review of available data on trials of modafinil as an adjuvant in the treatment of cognitive deficits, negative symptoms, and antipsychotic-induced fatigue, and its tolerability., CONCLUSIONS: While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia., The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms., Although preliminary, these results suggest modafinil may be an effective and well-tolerated adjunct treatment that improves global functioning and clinical condition, and reduces fatigue in patients with schizophrenia or schizoaffective disorder., While the available data suggest that modafinil is generally well tolerated and may have some efficacy in the treatment of antipsychotic-induced sedation and cognitive domains, the small sample sizes, contradictory results, and methodological differences between trials, especially with respect to cognitive testing, make it difficult to draw firm conclusions about the overall effectiveness of modafinil as an adjunct in the treatment of schizophrenia, The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms, Modafinil, a putative cognitive enhancing drug, has previously been shown to improve performance of healthy volunteers as well as patients with attention deficit disorder and schizophrenia, mainly in tests of executive functions[SEP]Relations: Modafinil has relations: contraindication with psychotic disorder, contraindication with psychotic disorder, contraindication with mental disorder, contraindication with mental disorder, drug_drug with Labetalol, drug_drug with Labetalol, drug_effect with Mania, drug_effect with Mania, drug_drug with Ethanol, drug_drug with Ethanol. Definitions: drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. sleepiness defined as following: Compelling urge to sleep.. schizoaffective disorder defined as following: A disorder in which the individual suffers from both symptoms that qualify as schizophrenia and symptoms that qualify as a mood disorder (e.g., depression or bipolar disorder) for a substantial portion (but not all) of the active period of the illness; for the remainder of the active period of the illness, the individual suffers from delusions or hallucinations in the absence of prominent mood symptoms.. memantine defined as following: AMANTADINE derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent.. D-serine defined as following: A non-essential amino acid and dextro isomer of serine with antipsychotic activity. D-serine is a selective full agonist at the glycine site of N-methyl-D-aspartate (NMDA)-type glutamate receptor. Hypofunction of NMDA type of neurotransmission is believed to play a major role in pathophysiology of schizophrenia, therefore, administration of D-serine and subsequent activation of NMDA receptors may alleviate psychotic tendencies.. clozapine defined as following: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.. traumatic brain injury defined as following: A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.. ADHD defined as following: A behavior disorder originating in childhood in which the essential features are signs of developmentally inappropriate inattention, impulsivity, and hyperactivity. Although most individuals have symptoms of both inattention and hyperactivity-impulsivity, one or the other pattern may be predominant. The disorder is more frequent in males than females. Onset is in childhood. Symptoms often attenuate during late adolescence although a minority experience the full complement of symptoms into mid-adulthood. (From DSM-V). 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). erythropoietin defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous glycoprotein erythropoietin (Epo). Epo promotes the differentiation and maturation of hematopoietic progenitors into erythrocytes; is a mitogen and a chemoattractant for endothelial cells; stimulates activated and differentiated B-cells and enhances B-cell immunoglobulin production and proliferation; and is hypoxia-inducible. (NCI04). modafinil defined as following: A benzhydryl acetamide compound, central nervous system stimulant, and CYP3A4 inducing agent that is used in the treatment of NARCOLEPSY and SLEEP WAKE DISORDERS.. celecoxib defined as following: A pyrazole derivative and selective CYCLOOXYGENASE 2 INHIBITOR that is used to treat symptoms associated with RHEUMATOID ARTHRITIS; OSTEOARTHRITIS and JUVENILE ARTHRITIS, as well as the management of ACUTE PAIN.. 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.. armodafinil defined as following: The R-enantiomer of the racemic synthetic agent modafinil with central nervous system (CNS) stimulant and wakefulness-promoting activities. Although the exact mechanism of action has yet to be fully elucidated, armodafinil appears to inhibit the reuptake of dopamine by binding to the dopamine-reuptake pump, which leads to an increase in extracellular dopamine levels in some brain regions. This agent does not bind to or inhibit several receptors and enzymes that may be involved in sleep/wake regulation and is not a direct- or indirect-acting dopamine receptor agonist. Armodafinil has a longer half-life than modafinil.. cognitive deficits defined as following: Disorders characterized by disturbances in mental processes related to learning, thinking, reasoning, and judgment.. trazodone defined as following: A serotonin uptake inhibitor that is used as an antidepressive agent. It has been shown to be effective in patients with major depressive disorders and other subsets of depressive disorders. It is generally more useful in depressive disorders associated with insomnia and anxiety. This drug does not aggravate psychotic symptoms in patients with schizophrenia or schizoaffective disorders. (From AMA Drug Evaluations Annual, 1994, p309). attention deficit disorder defined as following: A mental disorder characterized by inattention, easy distraction, careless mistakes and avoidance of tasks that require sustained mental focus. These behaviors can lead to maladaptive consequences in the affected individual's life.. weight gain defined as following: A question about whether an individual is gaining or has gained weight..", "label": "yes"}
{"id": "converted_1103", "sentence1": "Is miR-21 related to carcinogenesis?", "sentence2": "miR-21* and miR-203 were significantly dysregulated (P < 0.05) in PTC tissues with BRAFV600E., Expressions of miRNAs in papillary thyroid carcinoma and their associations with the BRAFV600E mutation., Levels of miRNA-21 (miR-21) and miR-106a in gastric cancer tissues were significantly higher compared with the levels in adjacent tissues (P = .006 and P = .001, respectively). Patients who had gastric cancer had significantly different levels of gastric juice miR-21 and miR-106a compared with patients who had benign gastric diseases (both P < .001)., miR-21 levels in intestinal type gastric cancer specimens were higher than that in diffuse (P = .003) or mixed (P < .001) gastric cancer types., MiR-155 and miR-21 appeared significantly over-expressed in the colonic mucosa of IBD subjects without CRC, but also in neoplastic tissues of IBD patients compared to non-IBD controls (p<0.001). Importantly, in patients with IBD-CRCs, miR-155 and miR-21 over-expression extended to the distant non-neoplastic mucosa (p<0.001)., Here we hypothesize that over-expression of miR-155 and miR-21, two inflammation-related miRNAs that target core MMR proteins, may constitute a pre-neoplastic event for the development of MSI IBD-CRCs., After administration, we determined the expressions of miR-21, miR-27a, miR-34a, miR-93, miR-143, miR-146a, miR-148a, miR-155, miR-196a, miR-203, miR-205, miR-221 and nuclear factor kappa-light-chain enhancer of activated B-cells-1 (Nfκb1), mitogen-activated protein kinase-8 (Mapk8) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-ras) genes in the liver of mice., Programmed cell death 4 (PDCD4) is a tumor suppressor gene whose expression is controlled by miR-21., Consistently with PDCD4 downregulation, miR-21 was upregulated in neoplastic by comparison with nonneoplastic tissue samples., Expression of miR-21 (p=0.027), miR-181b (p=0.002), and miR-146b (p=0.021) in tumor tissue and miR-21 (p=0.003) in noncancerous tissue were associated with patients' overall survival., We analyzed the expression of nine miRNAs (miR-21, miR-127, miR-154, miR-224, miR-323, miR-370, miR-9*, miR-183, and miR-375) by quantitative real-time-polymerase chain reaction in 34 cases of sMTC, 6 cases of hMTC, and 2 cases of C-cell hyperplasia (CCH)., MTC and CCH were both characterized by a significant overexpression of the whole set of miRNAs (the increase being 4.2-fold for miR-21, 6.7-fold for miR-127, 8.8-fold for miR-154, 6.6-fold for miR-224, 5.8-fold for miR-323, 6.1-fold for miR-370, 13-fold for miR-9*, 6.7-fold for miR-183, and 10.1 for miR-375, p<0.0001)., The most frequent changes in miRNAs in CLL cells included downregulation of miR-126, miR-572, miR-494, miR-923, miR-638, miR-130a, miR-181a and miR-181b and up-regulation of miR-29a, miR-660, miR-20a, miR-106b, miR-142-5p, miR-101, miR-30b, miR-34a, miR-let-7f, miR-21 and miR-155., Results: MTC and CCH were both characterized by a significant overexpression of the whole set of miRNAs (the increase being 4.2-fold for miR-21, 6.7-fold for miR-127, 8.8-fold for miR-154, 6.6-fold for miR-224, 5.8-fold for miR-323 and 6.1-fold for miR-370, 13-fold for miR-9*, 6.7-fold for miR-183 and 10.1 for miR-375, p<0.0001)., We found that the onco-miRNAs miR-21 and miR-221 displayed upregulated expression while the liver-specific miR-122 was downregulated., The aim of the present review was to describe the mechanisms of several known miR, summarize recent studies on oncogenic miR (e.g. miR-21, miR-106a and miR-17), tumor suppressor miR (e.g. miR-101, miR-181, miR-449, miR-486, let-7a) and controversial roles of miR (e.g. miR-107, miR-126) for gastric cancer., MiR-15b and miR-21 were differentially expressed in CSF samples from patients with gliomas, compared to control subjects with various neurologic disorders, including patients with primary CNS lymphoma and carcinomatous brain metastases., Moreover, inclusion of miR-15b and miR-21 in combined expression analyses resulted in an increased diagnostic accuracy with 90% sensitivity and 100% specificity to distinguish patients with glioma from control subjects and patients with primary CNS lymphoma., Many aberrantly expressed miRNAs were related to various cancers (e.g., miR-125b, hepatocellular carcinoma; miR-21, leukemia; miR-16, chronic lymphocytic leukemia; miR-192, pituitary adenomas; miR-199a-3p, ovarian cancer; miR-34a, pancreatic cancer). Several miRNAs (e.g., miR-34a, miR-21) and proteins (e.g., TGM2, NDRG2) that play crucial roles in liver tumorigenesis were first found to be affected by MC-LR in mouse liver., Except for miR-21 and miR-206, the expression levels of all miRNAs significantly changed during the progression of CaP., In addition, diet and carcinogen exposure modulated a number of microRNAs (miR-16, miR-19b, miR-21, miR26b, miR27b, miR-93, and miR-203) linked to canonical oncogenic signaling pathways., RESULTS: Elevated miR-21 (HR 2.06, 1.13-3.75), miR-17 (HR 2.00, 1.10-3.61), and miR-155 (HR 2.37, 1.27-4.42) was associated with worse cancer-specific mortality in the Maryland cohort., NF-κB targets miR-16 and miR-21 in gastric cancer: involvement of prostaglandin E receptors., Expression of miR-21, miR-29b, miR-34a/b/c, miR-155, and let-7a was determined by quantitative real-time PCR in formalin-fixed paraffin-embedded tumor specimens from 639 IALT patients., hese two miRNAs have previously been identified as being overexpressed in MCF-7 breast cancer cells, with miR-21 specifically implicated in down-regulating the tumor suppressor gene, tropomyosin-1., MicroRNA-21 is involved in ionizing radiation-promoted liver carcinogenesis., We showed here that among several hundred miRNAs, miR-21 was the only one that increased 6 folds in high-LET IR-promoted mouse liver tumors when compared with that in the non-irradiated liver tissues. We also showed that miR-21 was up-regulated in human or mouse hepatocytes after exposure to IR, as well as in liver tissues derived from whole body irradiated mice., After the non-irradiated, low-LET or high-LET irradiated human hepatocytes were over-expressed with miR-21, these cells became tumorigenesis in nude mice., METHODS: We used this combined ISH/IHC assay to study a subset of cancer-associated miRNAs, including miRNAs frequently detected at low (miR-34a and miR-126) and high (miR-21 and miR-155) levels, in a panel of breast, colorectal, lung, pancreas, and prostate carcinomas., The miR-15a, miR-16, miR-143, miR-155, and miR-21 were upregulated in M059K, and the modulation of these miRNAs fluctuated in M059J cells in a time-dependent manner., Aberrantly increased expression of miR-21 plays a significant role in lung carcinogenesis and is a potential therapeutic target in both epidermal growth factor receptor-mutant and wild-type cases., Additionally, high miR-21 expression was associated with significantly decreased 5 year survival in patients (hazard ratio, 1.68; 95% CI: 1.04-2.77) in a model controlled for patient age, gender and tumor stage., ESULTS: In adenocarcinoma patients, miR-21, miR-223, miR-192, and miR-194 expression was elevated, whereas miR-203 expression was reduced in cancerous compared with noncancerous tissue., Significantly, elevated miR-21 expression in noncancerous tissue of SCC patients and reduced levels of miR-375 in cancerous tissue of adenocarcinoma patients with Barrett's were strongly associated with worse prognosis., miR-21, mir-31, miR-130a, miR-146b and miR-377 were consistently upregulated, whereas miR-1 and miR-143 were downregulated in lung tumors relative to normal lungs. In mice treated with VC and given I3C in the diet, levels of miR-21, mir-31, miR-130a, miR-146b and miR-377 were reduced relative to the level in mice treated with the carcinogen only., Further studies with miR-21 indicated that phosphatase and tensin homolog, programmed cell death 4 and rich protein with Kazal motifs are potential targets for the oncogenic effect of miR-21 and the chemopreventive activity of I3C., This study examines the potential clinical utility of an inflammatory gene expression signature as a prognostic biomarker for colon cancer in addition to previously examined miR-21 expression., CONCLUSIONS: IRS and miR-21 expression are independent predictors of colon cancer prognosis and may provide a clinically useful tool to identify high-risk patients., The most highly expressed miRNAs in gastric cancer tissues were miR-20b, miR-20a, miR-17, miR-106a, miR-18a, miR-21, miR-106b, miR-18b, miR-421, miR-340*, miR-19a and miR-658., Recent findings report their involvement in hair follicle morphogenesis (ablation of miRNAs from keratinocytes causes several defects, such as evagination instead of invagination), in psoriasis (skin-specific expression of miR-203 and psoriasisspecific expression of miR-146a, miR-21 and miR-125b in the skin), in autoimmune diseases affecting the skin, such as SLE and ITP, in wound healing (changes in the expression of specific miRNA at specific phases of the regeneration process), and in skin carcinogenesis (a novel miRNA signature that includes induction of miR-21, a candidate oncogenic miRNA)., RESULTS: Several microRNAs were differentially expressed in serous ovarian carcinoma compared with normal ovarian tissues, including miR-21, miR-125a, miR-125b, miR-100, miR-145, miR-16, and miR-99a, which were each differentially expressed in >16 patients., Selected for validation were miR-20a, miR-21, miR-106a, miR-181b, and miR-203, and all 5 were enriched in tumors from the validation cohort (P < .001). Higher miR-21 expression was present in adenomas (P = .006) and in tumors with more advanced TNM staging (P < .001). In situ hybridization demonstrated miR-21 to be expressed at high levels in colonic carcinoma cells., To test this hypothesis, we studied the pharmacologic roles of three microRNAs previously implicated in cancer biology (let-7i, mir-16, and mir-21) and also used in silico methods to test pharmacologic microRNA effects more broadly., Changing the cellular levels of let-7i, mir-16, and mir-21 affected the potencies of a number of the anticancer agents by up to 4-fold. The effect was most prominent with mir-21, with 10 of 28 cell-compound pairs showing significant shifts in growth-inhibitory activity. Varying mir-21 levels changed potencies in opposite directions depending on compound class; indicating that different mechanisms determine toxic and protective effects. In silico comparison of drug potencies with microRNA expression profiles across the entire NCI-60 panel revealed that approximately 30 microRNAs, including mir-21, show highly significant correlations with numerous anticancer agents., Conversely, expression of other miRNAs was detected at varying levels predominantly within luminal epithelial cells in normal tissue; expression of miR-21 was frequently increased, whereas that of let-7a was decreased in malignant cells., We describe a novel EMT-specific microRNA signature that includes induction of miR-21, a candidate oncogenic microRNA associated with carcinogenesis., Notable was the high expression of miR-21 and miR-205., Recently, microRNAs (miRNAs) have emerged as key actors in carcinogenesis and we demonstrated that microRNA-21 (miR-21), oncomiR is expressed early during PDA., These results indicated that miR-21 plays a role in the carcinogenesis and metastasis of O. viverrini-associated CCA by suppressing the function of PDCD4., Importantly, in patients with IBD CRCs, miR-155 and miR-21 overexpression extended to the distant non-neoplastic mucosa (P < 0.001)., Ectopic overexpression of miR-21 promoted Akt activation and phosphorylation of EZH2, whereas inhibiting miR-21 by transfecting the cells with anti-miR-21 inhibited Akt activation and EZH2 phosphorylation., PDCD4 nuclear down-regulation (which parallels miR-21 up-regulation) is involved in the molecular pathway of IBD-associated carcinogenesis., The expression levels of miR-21 (p = 0.027), miR-181b (p = 0.002) and miR-146b (p = 0.021) in tumor tissue and miR-21 (p = 0.003) in noncancerous tissue were associated with overall survival of patients., OBJECTIVE: As an important oncogenic miRNA, miR-21 has been reported to play crucial roles in glioblastoma (GBM) carcinogenesis., We further analyzed the expression of microRNA-21 (miR-21), an oncogenic noncoding RNA involved in oncogenic Ras signaling, by quantitative reverse-transcription polymerase chain reaction and in situ hybridization., MicroRNA-21 (miR-21) plays crucial roles in carcinogenesis and is considered as one of the most studied oncomiRNAs., Although microRNA-21 (miR-21) has been implicated in various aspects of carcinogenesis, its functions and molecular mechanisms in carcinogen-induced tumorigenesis are unclear., Substantial evidence indicates that microRNA-21 (miR-21) is a key oncomiR in carcinogenesis and is significantly elevated in multiple myeloma (MM)., MicroRNA 21 (miR-21) has been implicated in various aspects of carcinogenesis., Conversely, pAkt and miR-21 expression was significantly up-regulated in the whole spectrum of preneoplastic/neoplastic lesions considered., Several miRNAs (e.g., miR-34a, miR-21) and proteins (e.g., TGM2, NDRG2) that play crucial roles in liver tumorigenesis were first found to be affected by MC-LR in mouse liver., RESULTS: Except for miR-21 and miR-206, the expression levels of all miRNAs significantly changed during the progression of CaP., MicroRNA 21 (miR-21) is overexpressed in virtually all types of carcinomas and various types of hematological malignancies., As expected, miR-21 expression was significantly upregulated in preneoplastic/neoplastic samples, consistent with PDCD4 downregulation., Furthermore, miR-21 levels in the primary tumours correlated with disease stage (P < 0.0001)., We found that miR-16 and miR-21 were upregulated upon nicotine stimulation, transfection with anti-miR-16 or anti-miR-21 significantly abrogated cell proliferation., MicroRNA-21 (miR-21) is a unique miRNA in that it is overexpressed in most tumour types analysed so far., Although altered expressions of miR-21 and miR-34a were manifested within cancer cells, those of miR-126 and miR-155 were predominantly confined to endothelial cells and immune cells, respectively., However, the function of miR-21 in osteosarcoma is still unclear., In SCC patients, we found elevated miR-21 and reduced miR-375 expression levels in cancerous compared with noncancerous tissue., miR-21, mir-31, miR-130a, miR-146b and miR-377 were consistently upregulated, whereas miR-1 and miR-143 were downregulated in lung tumors relative to normal lungs., Precancerous adenomas also frequently showed miR-21 up-regulation., Higher miR-21 expression was present in adenomas (P = .006), Importantly, the inflammatory ZD esophagus had a distinct microRNA signature resembling human ESCC or tongue SCC miRNAomes with miR-31 and miR-21 as the top-up-regulated species., Several miRNAs have been recently reported to be involved in modulation of glioma development, especially some upregulated miRNAs, such as microRNA-21 (miR-21), which has been found to function as an oncogene in cultured glioblastoma multiforme cells., OBJECTIVE: MicroRNA-21 (miR-21) is one of the miRNAs that are frequently and highly overexpressed in tumor tissue of colorectal cancer (CRC) patients; however, only a little is known about its functional role in CRC., Inhibition of microRNA-21 (mir‑21) induced upregulation of Spry2 and PTEN which underscores the importance of mir-21 in Spry2-associated tumorigenesis of the colon., The microRNA miR-21, a known oncogenic miRNA, was found to be upregulated in papillary and clear cell carcinomas., Since microRNA-21 (miR-21) may contribute to tumorigenesis and chemoresistance in many cancer types, we aimed to investigate its efficacy in TCCs., Several miRNAs have been recently reported to be involved in modulation of glioma development, especially some up-regulated miRNAs, such as microRNA-21 (miR-21), which has been found to function as an oncogene in cultured glioblastoma multiforme cells., In this study, by using high-throughput microRNA profiling, we identified that two miRNAs (miR-21 and miR-148a) overexpressed in CD4+ T cells from both patients with lupus and lupus-prone MRL/lpr mice, which promote cell hypomethylation by repressing DNA methyltransferase 1 (DNMT1) expression., The microRNA-21 (miR-21) has been identified as the only miRNA overexpressed in a variety of cancers, including leukemia., OBJECTIVE: The contribution of overexpressed microRNA-21 and -221 (miR-21 and miR-221) to the malignant phenotype was determined by inhibiting these miRNAs using antisense oligonucleotides., The microRNA-21(miR-21) has been identified as the only miRNA over-expressed in a wide variety of cancers, including cervical cancer., To determine the functions of these microRNAs in lymphomagenesis, we examined the effects of antisense oligonucleotides (ASOs) targeting miR-21 (ASO-21) and/or miR-155 (ASO-155) in NK-cell lymphoma lines overexpressing one or both of these miRNAs., In this study, microRNA (miRNA) expression profiling of 28 cases of never-smoker lung cancer identified aberrantly expressed miRNAs, which were much fewer than in lung cancers of smokers and included miRNAs previously identified (e.g., up-regulated miR-21) and unidentified (e.g., down-regulated miR-138) in those smoker cases., The oncogenic miRNA, microRNA-21 (miR-21), was found to be upregulated in laryngeal carcinoma tissues., OBJECTIVE: To better understand microRNA miR-21 function in carcinogenesis, we analyzed miR-21 expression patterns in different stages of colorectal cancer development using in situ hybridization (ISH)., Of these miRNAs, miR-21 appears to be important in tumorigenesis given its up-regulation in almost all types of human cancer examined., The microRNA-21 gene (mir-21) has been identified as the only miRNA commonly overexpressed in solid tumors of the lung, breast, stomach, prostate, colon, brain, head and neck, esophagus and pancreas., RESULTS: Our data showed that a common pattern of microRNA expression distinguishes any tumor type from normal pancreas, suggesting that this set of microRNAs might be involved in pancreatic tumorigenesis; the expression of miR-103 and miR-107, associated with lack of expression of miR-155, discriminates tumors from normal; a set of 10 microRNAs distinguishes endocrine from acinar tumors and is possibly associated with either normal endocrine differentiation or endocrine tumorigenesis; miR-204 is primarily expressed in insulinomas and correlates with immunohistochemical expression of insulin; and the overexpression of miR-21 is strongly associated with both a high Ki67 proliferation index and presence of liver metastasis., To search for tumor-associated mutations that could affect processing and expression of mature miRNAs, a panel of 91 cancer-derived cell lines was analyzed for sequence variations in 15 miRNAs implicated in tumorigenesis by virtue of their known target transcripts (let-7 family targeting oncogenic Ras) or their localization to sites of frequent chromosomal instability (miR-143, miR-145, miR-26a-1, and miR-21).[SEP]Relations: MIR122 has relations: disease_protein with hepatocellular carcinoma, disease_protein with hepatocellular carcinoma, disease_protein with pediatric hepatocellular carcinoma, disease_protein with pediatric hepatocellular carcinoma, disease_protein with drug-induced liver injury, disease_protein with drug-induced liver injury. lung has relations: anatomy_protein_present with MIR23B, anatomy_protein_present with MIR23B, anatomy_protein_present with MIR25, anatomy_protein_present with MIR25. Definitions: EZH2 defined as following: Histone-lysine N-methyltransferase EZH2 (746 aa, ~85 kDa) is encoded by the human EZH2 gene. This protein is involved in the regulation of chromatin modification.. miR-21 defined as following: This gene is involved in the regulation of gene expression and plays an oncogenic role in hepatocellular, breast, esophageal, gastric, pancreatic, prostatic and squamous cell carcinomas, glioblastoma and glioma.. miR-221 defined as following: Human MIR221 wild-type allele is located in the vicinity of Xp11.3 and is 109 bases in length. This allele, which encodes the MIR221 pre-miRNA, plays a role in the regulation of gene expression. Alteration in the expression of this gene is associated with the development of cancers of the liver, ovary, breast, lung, thyroid and prostate, as well as melanoma and glioblastoma multiforme.. leukemia defined as following: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006). gliomas defined as following: Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21). PTEN defined as following: Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (403 aa, ~47 kDa) is encoded by the human PTEN gene. This protein plays a role in signaling and as both a dual-specificity phosphoprotein phosphatase and a lipid phosphatase.. oncogene defined as following: Genes whose gain-of-function alterations lead to NEOPLASTIC CELL TRANSFORMATION. They include, for example, genes for activators or stimulators of CELL PROLIFERATION such as growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. A prefix of \"v-\" before oncogene symbols indicates oncogenes captured and transmitted by RETROVIRUSES; the prefix \"c-\" before the gene symbol of an oncogene indicates it is the cellular homolog (PROTO-ONCOGENES) of a v-oncogene.. DNMT1 defined as following: Human DNMT1 wt allele is located in the vicinity of 19p13.2 and is approximately 62 kb in length. This allele, which encodes DNA (Cytosine-5)-Methyltransferase 1, is involved in epigenetic modification of chromatin DNA and control of gene expression.. Mapk8 defined as following: Mitogen-activated protein kinase 8 (427 aa, ~48 kDa) is encoded by the human MAPK8 gene. This protein plays a role in serine/threonine phosphorylation, apoptosis and toll-like receptor signaling.. gastric cancer defined as following: A primary or metastatic malignant neoplasm involving the stomach.. miR-31 defined as following: Human MIR31 wild-type allele is located in the vicinity of 9p21.3 and is approximately 0.1 kb in length. This allele, which encodes MIR31 pre-miRNA, may be involved in both tumor suppression and the modulation of transcription.. Akt defined as following: Expressed in diverse tissues, Protein Kinase B (AKT/RAC Family) is a group (Alpha, Beta and Gamma) of cytoplasmic serine/threonine enzymes that covalently transfer the terminal, gamma phosphate group from ATP to a variety of substrate proteins and regulate cell signaling responses to insulin, PDGF, and IGF1 (through PI3K) involved in cell survival, cell proliferation, differentiation, apoptosis, glycogen synthesis, and glucose uptake.. clear cell carcinomas defined as following: An adenocarcinoma characterized by the presence of varying combinations of clear and hobnail-shaped tumor cells. There are three predominant patterns described as tubulocystic, solid, and papillary. These tumors, usually located in the female reproductive organs, have been seen more frequently in young women since 1970 as a result of the association with intrauterine exposure to diethylstilbestrol. (From Holland et al., Cancer Medicine, 3d ed). multiple myeloma defined as following: A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.. miR-181 defined as following: A microRNA that has six isoforms that may play a role in the activity of phosphatidylinositol-4,5-bisphosphate 3-kinase and natural killer cells. The MIR181 isoforms have been implicated in a variety of cancers, including chronic lymphocytic leukemia, glioblastoma, multiple myeloma and hepatocellular carcinoma.. miR-145 defined as following: This gene is involved in the regulation of gene expression and plays a role in the development of colorectal and prostate carcinomas as well as chronic lymphocytic leukemia, Burkitt lymphoma and diffuse large B-cell lymphoma.. tropomyosin-1 defined as following: Tropomyosin alpha-1 chain (284 aa, ~33 kDa) is encoded by the human TPM1 gene. This protein plays a role in muscle contraction.. 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.. microRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. Spry2 defined as following: Protein sprouty homolog 2 (315 aa, ~35 kDa) is encoded by the human SPRY2 gene. This protein is involved in antagonism of growth factor signaling pathways.. serous ovarian carcinoma defined as following: An adenocarcinoma that arises from the ovary and is characterized by the presence of malignant epithelial cells that, in well differentiated tumors, resemble the epithelium of the fallopian tube or, in poorly differentiated tumors, show anaplastic features and marked nuclear atypia.. pancreatic cancer defined as following: A primary or metastatic malignant tumor involving the pancreas. Representative examples include carcinoma and lymphoma.. MMR defined as following: A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the BASE PAIR MISMATCH and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001). lung tumors defined as following: Tumors or cancer of the LUNG.. liver tumors defined as following: Tumors or cancer of the LIVER.. 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.. Kazal motifs defined as following: Highly conserved protein domains characteristic of SERINE PROTEASE INHIBITORS, KAZAL TYPE. They generally occur as tandem repeats, with each domain consisting of approximately 60 amino acids that form a large extended amino acid chain, two short ALPHA-HELICES, and a three-stranded anti-parallel BETA-SHEET. Kazal-like domains also occur in the extracellular portions of AGRIN.. DNA methyltransferase 1 defined as following: Enzymes that are part of the restriction-modification systems. They are responsible for producing a species-characteristic methylation pattern, on either adenine or cytosine residues, in a specific short base sequence in the host cell's own DNA. This methylated sequence will occur many times in the host-cell DNA and remain intact for the lifetime of the cell. Any DNA from another species which gains entry into a living cell and lacks the characteristic methylation pattern will be recognized by the restriction endonucleases of similar specificity and destroyed by cleavage. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms.. 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.. PDCD4 defined as following: Programmed cell death protein 4 (469 aa, ~52 kDa) is encoded by the human PDCD4 gene. This protein may be involved in the regulation of both apoptosis and translation.. human defined as following: Members of the species Homo sapiens.. hematological malignancies defined as following: Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.. insulinomas defined as following: A benign tumor of the PANCREATIC BETA CELLS. Insulinoma secretes excess INSULIN resulting in HYPOGLYCEMIA.. ITP defined as following: Thrombocytopenia occurring in the absence of toxic exposure or a disease associated with decreased platelets. It is mediated by immune mechanisms, in most cases IMMUNOGLOBULIN G autoantibodies which attach to platelets and subsequently undergo destruction by macrophages. The disease is seen in acute (affecting children) and chronic (adult) forms.. miR-223 defined as following: The human MIR223 wild-type allele is located in the vicinity of Xq12 and is 109 bases in length. This allele, which encodes MIR223 RNA, plays a role in development of cancers of the liver and ovary, acute promyelocytic leukemia and chronic myeloid leukemia.. colonic carcinoma defined as following: A malignant epithelial neoplasm that arises from the colon and invades through the muscularis mucosa into the submucosa. The vast majority are adenocarcinomas.. lungs defined as following: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.. endothelial cells defined as following: Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.. CNS lymphoma defined as following: A non-Hodgkin or Hodgkin lymphoma that arises in the brain or spinal cord as a primary lesion. There is no evidence of lymphoma outside the central nervous system at the time of diagnosis.. tumor tissue defined as following: A tumor sample, or entire tumor that is removed for microscopic examination.. keratinocytes defined as following: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell.. cervical cancer defined as following: A primary or metastatic malignant neoplasm involving the cervix.. colon cancer defined as following: A primary or metastatic malignant neoplasm that affects the colon. Representative examples include carcinoma, lymphoma, and sarcoma.. gastric juice defined as following: The liquid secretion of the stomach mucosa consisting of hydrochloric acid (GASTRIC ACID); PEPSINOGENS; INTRINSIC FACTOR; GASTRIN; MUCUS; and the bicarbonate ion (BICARBONATES). (From Best & Taylor's Physiological Basis of Medical Practice, 12th ed, p651). HR defined as following: The rapid, localized death of plant cells in response to invasion by a pathogen. [ISBN:0582227089]. NDRG2 defined as following: This gene is involved in the regulation of cellular differentiation.. 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.. cancer cells defined as following: Cells of, or derived from, a malignant tumor.. miR-181b defined as following: A 23 ribonucleotide sequence that is a final product of the processing of either MIR181B1 pre-miRNA or MIR181B2 pre-miRNA. This oligonucleotide may be involved in the negative regulation of gene expression.. 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.. MSI defined as following: The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.. carcinomas defined as following: A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm and not a synonym for \"cancer.\". TGM2 defined as following: Protein-glutamine gamma-glutamyltransferase 2 (687 aa, ~77 kDa) is encoded by the human TGM2 gene. This protein plays a role in both the induction of apoptosis and the formation of covalent bonds between peptide-bound glutamine and various primary amines.. miR-16 defined as following: A 22 ribonucleotide sequence that is a final product of the processing of either MIR16-1 pre-miRNA or MIR16-2 pre-miRNA. This oligonucleotide may be involved in the negative regulation of gene expression.. chronic lymphocytic leukemia defined as following: A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.. pituitary adenomas defined as following: A non-metastasizing tumor that arises from the adenohypophysial cells of the anterior lobe of the pituitary gland. The tumor can be hormonally functioning or not. The diagnosis can be based on imaging studies and/or radioimmunoassays. Due to its location in the sella turcica, expansion of the tumor mass can impinge on the optic chiasm or involve the temporal lobe, third ventricle and posterior fossa A frequently associated physical finding is bitemporal hemianopsia which may progress to further visual loss.. antisense oligonucleotides defined as following: Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize.. 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.. nicotine defined as following: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.. let-7 defined as following: A microRNA that has seven isofoms and is known to be a regulator of the RAS oncogene. The length of the miRNA is ~22 nucleotides, and the 3' UTR is the mechanistic path of regulation. The let-7 isoforms have been implicated in a variety of cancers, including lung and breast.. ovarian cancer defined as following: A primary or metastatic malignant neoplasm involving the ovary. Most primary malignant ovarian neoplasms are either carcinomas (serous, mucinous, or endometrioid adenocarcinomas) or malignant germ cell tumors. Metastatic malignant neoplasms to the ovary include carcinomas, lymphomas, and melanomas.. miR-203 defined as following: The human MIR203A wild-type allele is located in the vicinity of 14q32.33 and is approximately 110 bases in length. This allele, which encodes MIR203A pre-miRNA, plays a role in the regulation of gene expression. Alteration in the expression of this gene is associated with development of acute lymphoblastic leukemia, chronic myeloid leukemia and psoriasis.. Ras defined as following: A family of oncogenes that are highly homologous with the retrovirus-associated DNA sequences (ras) originally isolated from Harvey and Kirsten murine sarcoma viruses. Mutated or overexpressed forms of the human ras genes are associated with constitutive ras GTPase activity, increased cellular proliferation, and cell transformation.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. toxic defined as following: The finding of bodily harm due to the poisonous effects of something.. 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). 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.. 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.. osteosarcoma defined as following: A usually aggressive malignant bone-forming mesenchymal neoplasm arising from the bone. It may arise de novo or from a pre-existing lesion of the bone. Pain and a palpable mass are the most frequent clinical sign and symptom. It may spread to other anatomic sites, particularly the lungs.. prostaglandin E receptors defined as following: Cell surface receptors which bind prostaglandins with a high affinity and trigger intracellular changes which influence the behavior of cells. Prostaglandin E receptors prefer prostaglandin E2 to other endogenous prostaglandins. They are subdivided into EP1, EP2, and EP3 types based on their effects and their pharmacology.. miR-19b defined as following: A 23 ribonucleotide sequence that is a final product of the processing of either MIR19B1 pre-miRNA or MIR19B2 pre-miRNA. This oligonucleotide may be involved in the negative regulation of gene expression.. IBD defined as following: Gastrointestinal symptoms characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause.. I3C defined as following: A naturally occurring, orally available cleavage product of the glucosinolate glucobrassicanin, a natural compound present in a wide variety of plant food substances including members of the family Cruciferae with antioxidant and potential chemopreventive properties. Indole-3-carbinol scavenges free radicals and induces various hepatic cytochrome P450 monooxygenases. Specifically, this agent induces the hepatic monooxygenase cytochrome P4501A1 (CYP1A1), resulting in increased 2-hydroxylation of estrogens and increased production of the chemoprotective estrogen 2-hydroxyestrone.. C-cell hyperplasia defined as following: Neoplastic or reactive proliferation of the C-cells in the thyroid gland. The neoplastic C-cell hyperplasia is associated with familial medullary thyroid gland carcinoma and multiple endocrine neoplasia type II and IIB. Morphologically, it is characterized by the presence of clusters of intrafollicular C-cells with atypical cytologic features. The reactive C-cell hyperplasia is also known as physiological or secondary C-cell hyperplasia and it is associated with conditions that cause hypercalcemia (e.g., hyperparathyroidism).. PDA defined as following: Branch of right coronary artery which runs along the upper third of the posterior interventricular sulcus to supply the posterior wall of right and left ventricles and the posterior third of the interventricular septum.. 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.. CRC defined as following: The disappearance of all signs of cancer, including the absence of a detectable disease-related genetic abnormality, as determined by techniques such as karyotyping or FISH, in response to treatment.. head and neck defined as following: For oncology, an area of the body generally construed to comprise the base of skull and facial bones, sinuses, orbits, salivary glands, oral cavity, oropharynx, larynx, thyroid, facial and neck musculature and lymph nodes draining these areas.. MTC defined as following: A neuroendocrine carcinoma arising from the C-cells of the thyroid gland. It is closely associated with multiple endocrine neoplasia syndromes. Approximately 10% to 20% of medullary thyroid carcinomas are familial. Patients usually present with a thyroid nodule that is painless and firm. In the majority of cases nodal involvement is present at diagnosis. Surgery is the preferred treatment for both primary lesions and recurrences. This carcinoma is generally not very sensitive to radiation and almost unresponsive to chemotherapy.. liver tissues defined as following: The tissue of the liver. It includes the hepatic lobules, hepatic sinusoids, perisinusoidal spaces, and portal triad. The hepatic lobules are composed of hepatocytes.. 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.. GBM defined as following: A sheet of amorphous extracellular material upon which the basal surfaces of epithelial cells rest and is the covering surface of a glomerular capillary, interposed between the cellular elements and the underlying connective tissue.. miR-206 defined as following: The human MIR206 wild-type allele is located in the vicinity of 6p12.2 and is approximately 85 bases in length. This allele, which encodes MIR206 pre-miRNA, plays a role in the regulation of gene expression. Alteration in the expression of this gene is associated with development of breast cancer and schizophrenia.. papillary defined as following: Of or relating to or resembling papilla.. lung cancers defined as following: A primary or metastatic malignant neoplasm involving the lung.. lupus defined as following: chronic form of cutaneous lupus erythematosus in which the skin lesions mimic those of the systemic form but in which systemic signs are rare; characterized by the presence of discoid skin plaques showing varying degrees of edema, erythema, scaliness, follicular plugging, and skin atrophy; lesions are surrounded by an elevated erythematous border; the condition typically involves the face and scalp, but widespread dissemination may occur.. adenomas defined as following: A benign epithelial tumor with a glandular organization.. MM defined as following: A unit of concentration (molarity unit) equal to one thousandth of a mole (10E-3 mole) of solute per one liter of solution.. miR-122 defined as following: This gene is involved in the regulation of gene expression and plays a role in the development of hepatocellular carcinoma.. laryngeal carcinoma defined as following: Carcinoma that arises from the laryngeal epithelium. More than 90% of laryngeal carcinomas are squamous cell carcinomas. The remainder are adenoid cystic carcinomas, mucoepidermoid carcinomas and carcinomas with neuroendocrine differentiation.. miR-181a defined as following: A 23 ribonucleotide sequence that is a final product of the processing of either MIR181A1 pre-miRNA or MIR181A2 pre-miRNA. This oligonucleotide may be involved in the negative regulation of gene expression.. 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.. 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.. SLE defined as following: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow..", "label": "yes"}
{"id": "converted_4530", "sentence1": "Are functional tests a good biomarker for Duchenne Muscular Dystrophy?", "sentence2": "North Star Ambulatory Assessment is practical and reliable., allow assessment of high-functioning boys with Duchenne muscular dystrophy., agnosis and tracking of symptom progression of DMD usually relies on creatine kinase tests, evaluation of patient performance in various ambulatory assessments, and detection of dystrophin from muscle biopsies, which are invasive and painful for the patient. While the, Aim: Using baseline data from a clinical trial of domagrozumab in Duchenne muscular dystrophy, we evaluated the correlation between functional measures and quantitative MRI assessments of thigh muscle. Patients & methods: Analysis included timed functional tests, knee extension/strength and North St, A New Functional Scale and Ambulatory Functional Classification of Duchenne Muscular Dystrophy: Scale Development and Preliminary Analyses of Reliability and Validity., his preliminary investigation describes the relationship between community ambulation measured by the StepWatch activity monitor and the current standard of functional assessment, the 6-minute walk test, in ambulatory boys with Duchenne muscular dystrophy (n = 16) and healthy controls (n = 13). All, ith strength assessments. MV index, fat fraction and T2-mapping measures had moderate correlations (r ∼ 0.5) to all functional tests, North Star Ambulatory Assessment and age. Conclusion: The moderate correlation between functional tests, age and baseline MRI measures supports MRI as a biomarker in Duchenn, on with clinically meaningful outcome measures such as North Star Ambulatory Assessment (NSAA) and 6 minute walk test (6MWT) is paramount for biomarker qualification. In this stu, Quantitative muscle strength assessment in duchenne muscular dystrophy: longitudinal study and correlation with functional measures., The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration, Conclusion: The moderate correlation between functional tests, age and baseline MRI measures supports MRI as a biomarker in Duchenne muscular dystrophy clinical trials., Currently, functional measures continue to serve as the primary outcome for the majority of DMD clinical trials., Patients & methods: Analysis included timed functional tests, knee extension/strength and North Star Ambulatory Assessment., The 6-minute walk test, timed 10-meter walk/run test, and supine-up time are commonly used timed functional tests that also sufficiently monitor changes in muscle function; however, they strongly depend on patient collaboration., We have developed a new scale and the associated classification system, to assess the functional ability of children diagnosed with DMD. Preliminary evaluation of the psychometric properties of the functional scale and classification systems indicate sufficient reliability and concurrent validity., Quantitative MRI is an objective and sensitive biomarker to detect subclinical changes, though the examination costs may be a reason for its limited use. In this study, a high correlation between all clinical assessments and quantitative MRI scans was found. The combinational use of these methods provides a better understanding about disease progression; however, longitudinal studies are needed to validate their reliability., The children's functional performance was assessed using 6-minute walk tests and timed performance tests. The correlations between the flexibilities of the lower limb muscles and the performance tests were examined., The flexibilities of the lower extremity muscles were found to be correlated to the 6-minute walk tests and the timed performance tests. The flexibility of the hamstrings (r = -.825), the gastrocnemius muscles (r = .545), the hip flexors (r = .481), and the tensor fascia latae (r = .445) were found to be correlated with functional performance as measured by the 6-minute walk tests (P < .05), Nine biomarkers have been identified that correlate with disease milestones, functional tests and respiratory capacity. Together these biomarkers recapitulate different stages of the disorder that, if validated can improve disease progression monitoring., In conclusion, the motor function measure and timed function tests measure disease severity in a highly comparable fashion and all tests correlated with quantitative muscle MRI values quantifying fatty muscle degeneration., This study is to date the most thorough long-term evaluation of QMT in a cohort of DMD patients correlated with other measures, such as the North Star Ambulatory Assessment (NSAA) or three 6-min walk test (6MWT)., The MFM scale was a useful instrument in the follow up of patients with DMD. Moreover, it is a more comprehensive scale to assess patients and very good for conducting trials to evaluate treatment., MD subjects were evaluated using the Vignos lower extremity functional rating, and tests including 6 min walk test (6MWT) and 10 m walk., TFTs appear to be slightly more responsive and predictive of disease progression than the 6MWT in 7-12.9 year olds., herefore, in our group of ambulant patients with DMD, timed functional testing was the most sensitive parameter to determine the extent of disease progression. Timed functional testing may therefore be considered as an additional outcome measure in drug trials to evaluate the effects of therapy in ambulant patients with DMD and possibly in other neuromuscular disorders., Time to rise is a useful and simple tool in the screening of neuromuscular disorders such as Duchenne muscular dystrophy,, he muscle strength of the wrist extensors and the radial deviation range of motion at the wrist were found to be strongly correlated with six of the seven tasks assessed. These two clinical assessments appear to be good indicators of overall wrist and hand function.[SEP]Relations: Duchenne muscular dystrophy has relations: disease_phenotype_positive with Muscular dystrophy, disease_phenotype_positive with Muscular dystrophy, disease_phenotype_positive with Skeletal muscle atrophy, disease_phenotype_positive with Skeletal muscle atrophy, disease_protein with BCHE, disease_protein with BCHE, disease_protein with DMD, disease_protein with DMD, disease_protein with ACHE, disease_protein with ACHE. Definitions: gastrocnemius muscles defined as following: A large muscle in the back of the lower leg. Its action involves the plantar flexion of the foot.. DMD defined as following: An X-linked recessive muscle disease caused by an inability to synthesize DYSTROPHIN, which is involved with maintaining the integrity of the sarcolemma. Muscle fibers undergo a process that features degeneration and regeneration. Clinical manifestations include proximal weakness in the first few years of life, pseudohypertrophy, cardiomyopathy (see MYOCARDIAL DISEASES), and an increased incidence of impaired mentation. Becker muscular dystrophy is a closely related condition featuring a later onset of disease (usually adolescence) and a slowly progressive course. (Adams et al., Principles of Neurology, 6th ed, p1415). dystrophin defined as following: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as SPECTRIN and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa.. NSAA defined as following: A standardized 17-item scale that was developed by Elaine Scott and Michelle Eagle in 2011 to measure functional motor ability in ambulant children and adolescents with Duchenne muscular dystrophy. The instrument, which is partly based on the Hammersmith Motor Ability Scale (2003), utilizes a 3-point rating scale to grade activities ranging from standing to running, as well as abilities that are necessary for a patient to remain functionally ambulant and that are known to progressively deteriorate in untreated DMD.. neuromuscular disorders defined as following: A general term encompassing lower MOTOR NEURON DISEASE; PERIPHERAL NERVOUS SYSTEM DISEASES; and certain MUSCULAR DISEASES. Manifestations include MUSCLE WEAKNESS; FASCICULATION; muscle ATROPHY; SPASM; MYOKYMIA; MUSCLE HYPERTONIA, myalgias, and MUSCLE HYPOTONIA.. muscle biopsies defined as following: Removal of tissue from the muscle, for microscopic examination..", "label": "yes"}
{"id": "converted_2916", "sentence1": "Is there any role for HUWE1 in MYC signalling?", "sentence2": "HUWE1 is a critical colonic tumour suppressor gene that prevents MYC signalling, DNA damage accumulation and tumour initiation., To determine the importance of HUWE1, we chose to examine its function in colorectal cancer, where it is mutated in up to 15 per cent of tumours. Modelling of identified mutations showed that they inactivate the E3 ubiquitin ligase activity of HUWE1. Genetic deletion of Huwe1 rapidly accelerated tumourigenic in mice carrying loss of the intestinal tumour suppressor gene Apc, with a dramatic increase in tumour initiation. Mechanistically, this phenotype was driven by increased MYC and rapid DNA damage accumulation leading to loss of the second copy of Apc The increased levels of DNA damage sensitised Huwe1-deficient tumours to DNA-damaging agents and to deletion of the anti-apoptotic protein MCL1. Taken together, these data identify HUWE1 as a bona fide tumour suppressor gene in the intestinal epithelium and suggest a potential vulnerability of HUWE1-mutated tumours to DNA-damaging agents and inhibitors of anti-apoptotic proteins.[SEP]Relations: receptor signaling protein tyrosine kinase inhibitor activity has relations: molfunc_protein with HYAL2, molfunc_protein with HYAL2. regulation of intestinal epithelial structure maintenance has relations: bioprocess_protein with NEUROD1, bioprocess_protein with NEUROD1. anus neoplasm has relations: disease_protein with IFNB1, disease_protein with IFNB1. Protein S human has relations: drug_drug with Peginterferon beta-1a, drug_drug with Peginterferon beta-1a, drug_drug with Peginterferon beta-1a, drug_drug with Peginterferon beta-1a. Definitions: HUWE1 defined as following: E3 ubiquitin-protein ligase HUWE1 (4374 aa, ~482 kDa) is encoded by the human HUWE1 gene. This protein is involved in the modulation of ubiquitination of target proteins involved in DNA replication and repair, apoptosis, chromatin remodeling, circadian rhythms and tumor suppression.. tumour defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. MYC defined as following: Myc proto-oncogene protein (439 aa, ~49 kDa) is encoded by the human MYC gene. This protein plays a role in the regulation of transcription and cell proliferation.. tumour suppressor gene defined as following: Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.. mutated defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer..", "label": "yes"}
{"id": "converted_1535", "sentence1": "Are immune cells affected in Amyotrophic Lateral Sclerosis?", "sentence2": "Therapeutic immunization of mSOD1 mice with a myelin-derived peptide led to CP activation, and was followed by the accumulation of immunoregulatory cells, including IL-10-producing monocyte-derived macrophages and Foxp3(+) regulatory T cells, and elevation of the neurotrophic factors IGF-1 and GDNF in the diseased spinal cord parenchyma, Immunization with a Myelin-Derived Antigen Activates the Brain's Choroid Plexus for Recruitment of Immunoregulatory Cells to the CNS and Attenuates Disease Progression in a Mouse Model of ALS., Amyotrophic lateral sclerosis (ALS) is a rapidly progressing fatal neurodegenerative disorder characterized by the selective death of motor neurons (MN) in the spinal cord, and is associated with local neuroinflammation., T-cell deficiency increases neuronal loss, while boosting T cell levels reduces it., As disease accelerates, a shift occurs from beneficial immune responses (involving M2 microglia and regulatory T-cells) to deleterious immune responses (involving M1 microglia and Th1 cells). In this review, we underscore the importance of immune-mediated mechanisms in the pathogenesis of ALS and discuss the alterations and distinct phenotypes of immune cells at the different stages of disease., Immunological disturbances have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Chemokines are involved in the recruitment of immune cells., The immune system has been found to be involved with positive and negative effects in the nervous system of amyotrophic lateral sclerosis (ALS) patients. In general, T cells, B cells, NK cells, mast cells, macrophages, dendritic cells, microglia, antibodies, complement and cytokines participate in limiting damage., Immunological disturbances have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Chemokines are involved in the recruitment of immune cells., We propose the following mechanism for the effect of mesenchymal stem cells (MSCs) administered intrathecally in amyotrophic lateral sclerosis (ALS): MSCs increase infiltration of peripheral immune cells into CNS and skew the infiltrated immune cells toward regulatory T lymphocytes (Treg ) and Th2 lymphocytes., Immune cell infiltration to the brain's territory was considered for decades to reflect a pathological process in which immune cells attack the central nervous system (CNS); such a process is observed in the inflammatory autoimmune disease, multiple sclerosis (MS).[SEP]Relations: amyotrophic lateral sclerosis has relations: disease_disease with familial amyotrophic lateral sclerosis, disease_disease with familial amyotrophic lateral sclerosis, disease_disease with motor neuron disease, disease_disease with motor neuron disease, disease_protein with FIG4, disease_protein with FIG4, disease_protein with OTOG, disease_protein with OTOG, disease_disease with progressive muscular atrophy, disease_disease with progressive muscular atrophy. Definitions: amyotrophic lateral sclerosis defined as following: A degenerative disorder affecting upper MOTOR NEURONS in the brain and lower motor neurons in the brain stem and SPINAL CORD. Disease onset is usually after the age of 50 and the process is usually fatal within 3 to 6 years. Clinical manifestations include progressive weakness, atrophy, FASCICULATION, hyperreflexia, DYSARTHRIA, dysphagia, and eventual paralysis of respiratory function. Pathologic features include the replacement of motor neurons with fibrous ASTROCYTES and atrophy of anterior SPINAL NERVE ROOTS and corticospinal tracts. (From Adams et al., Principles of Neurology, 6th ed, pp1089-94). 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.. dendritic cells defined as following: Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).. microglia defined as following: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling.. NK cells defined as following: Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.. mast cells defined as following: Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the BASOPHILS, mast cells contain large amounts of HISTAMINE and HEPARIN. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the STEM CELL FACTOR.. neurodegenerative disorder defined as following: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.. spinal cord defined as following: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.. 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.. regulatory T-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.. Chemokines defined as following: Formulated therapeutic analogs of one of a number of endogenous small polypeptide cytokines with potential antineoplastic activity. Synthesized by macrophages, endothelial cells, keratinocytes, fibroblasts, and smooth muscle cells, chemokines are released in the presence of infection or physical tissue damage, and act as chemoattractants to recruit macrophages, neutrophils, and T cells from the blood to sites of infection or damage. These agents may regulate tumor growth by modulating tumor-associated angiogenesis and metastasis and can either promote or retard tumor growth. (NCI04). IGF-1 defined as following: A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.. GDNF defined as following: The founding member of the glial cell line-derived neurotrophic factor family. It was originally characterized as a NERVE GROWTH FACTOR promoting the survival of MIDBRAIN dopaminergic NEURONS, and it has been studied as a potential treatment for PARKINSON DISEASE.. Immune cell defined as following: A cell in the immune system that is involved in host defense. This category may include lymphocytes, monocytes, macrophages, neutrophils, eosinophils, basophils, mast cells, and thrombocytes. Precursor cells in these lineages may also be included.. MN defined as following: A system of universal human blood group isoantigens with many associated subgroups. The M and N traits are codominant and the S and s traits are probably very closely linked alleles, including the U antigen. This system is most frequently used in paternity studies.. Th1 cells defined as following: A subset of helper-inducer T-lymphocytes which synthesize and secrete INTERLEUKIN-2; INTERFERON-GAMMA; and INTERLEUKIN-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.. B cells defined as following: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.. mesenchymal stem cells defined as following: An undifferentiated stromal cell with the ability to develop into the cells that form distinct mesenchymal tissues; such as bone, muscle, connective tissue, blood vessels, and lymphatic tissue.. 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). 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]. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. motor neurons defined as following: Neurons which send impulses peripherally to activate muscles or secretory cells..", "label": "yes"}
{"id": "converted_1880", "sentence1": "Are alterations in ultraconserved elements implicated in breast cancer?", "sentence2": "SNPs in ultraconserved elements and familial breast cancer risk, In the present study, we investigated the influence of six SNPs within UCEs on familial breast cancer risk. Two out of six SNPs showed an association with familial breast cancer risk, This is the first study indicating that SNPs in UCEs might be associated with cancer risk, SNPs in ultraconserved elements and familial breast cancer risk., Recent studies have indicated that UCEs are not mutation cold regions and likely to be concerned with cancers, including breast cancer (BC). , SNPs in ultraconserved elements and familial breast cancer risk., Genetic variants in ultraconserved elements and risk of breast cancer in Chinese population.[SEP]Relations: breast-ovarian cancer, familial, susceptibility to has relations: disease_protein with RAD51D, disease_protein with RAD51D, disease_protein with RAD51C, disease_protein with RAD51C, disease_phenotype_positive with Breast carcinoma, disease_phenotype_positive with Breast carcinoma, disease_phenotype_positive with Multifactorial inheritance, disease_phenotype_positive with Multifactorial inheritance, disease_phenotype_positive with Ovarian carcinoma, disease_phenotype_positive with Ovarian carcinoma. Definitions: 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.. SNPs defined as following: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.. 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.. familial breast cancer defined as following: Breast carcinoma that has developed in relatives of patients with history of breast carcinoma.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer..", "label": "yes"}
{"id": "converted_2409", "sentence1": "Are mouse chromosomes acrocentric?", "sentence2": " Based on combined fluorescence in situ hybridization and linkage mapping, the gene order on CFA9 is similar to that of the homologous genes on HSA17q and mouse chromosome 11 (MMU11), but in the dog the gene order is inverted with respect to the centromere. , In murine models of human carcinogenesis, however, karyotype analysis is technically demanding because mouse chromosomes are acrocentric and of similar size., The minor satellite is closer to the short arms of the acrocentric chromosomes than the major satellite, These cells contain Robertsonian translocated chromosomes 1 and 7 as the only submetacentric chromosome in an otherwise acrocentric genome., The resulting metacentric chromosomes are very different in size and in morphology from normal mouse acrocentric chromosomes., Because of 35 independent primary hybrids used in this study were derived from two types of feral mice, each with a different combination of Robertsonian translocation chromosomes, as well as from mice with a normal complement of acrocentric chromosomes, analysis of 16 selected mouse enzyme markers provided data on the segregation of all 20 mouse chromosomes in these hybrids, The two mouse stocks exhibit karyotypes consisting of nine pairs of metacentric chromosomes as a result of centric fusions of acrocentric chromosomes in different combinations., Physical gene mapping by in situ hybridization is a difficult task in an all-acrocentric mouse karyotype, because all of the chromosomes are morphologically very similar., The resulting metacentric chromosomes are very different in size and in morphology from normal mouse acrocentric chromosomes., murine models of human carcinogenesis are exceedingly valuable tools to understand genetic mechanisms of neoplastic growth the identification of recurrent chromosomal rearrangements by cytogenetic techniques serves as an initial screening test for tumour specific aberrations in murine models of human carcinogenesis however karyotype analysis is technically demanding because mouse chromosomes are acrocentric and of similar size fluorescence in situ hybridization fish with mouse chromosome specific painting probes can complement conventional banding analysis although sensitive and specific fish analyses are restricted to the visualization of only a few mouse chromosomes at a time here we apply a novel imaging technique that we developed recently for the visualization of human chromosomes to the simultaneous discernment of all mouse chromosomes the approach is based on spectral imaging to measure chromosome specific spectra after fish with differentially labelled mouse chromosome painting probes utilizing a combination of fourier spectroscopy ccd imaging and conventional optical microscopy spectral imaging allows simultaneous measurement of the fluorescence emission spectrum at all sample points a spectrum based classification algorithm has been adapted to karyotype mouse chromosomes we have applied spectral karyotyping sky to chemically induced plasmocytomas mammary gland tumours from transgenic mice overexpressing the c myc oncogene and thymomas from mice deficient for the ataxia telangiectasia atm gene results from these analyses demonstrate the potential of sky to identify complex chromosomal aberrations in mouse models of human carcinogenesis.[SEP]Relations: chromosome has relations: cellcomp_protein with MBD6, cellcomp_protein with MBD6, cellcomp_protein with HOXA13, cellcomp_protein with HOXA13, cellcomp_protein with TEX12, cellcomp_protein with TEX12, cellcomp_protein with CBX6, cellcomp_protein with CBX6, cellcomp_protein with CCDC86, cellcomp_protein with CCDC86. Definitions: tumour defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. chromosomal defined as following: In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). fish defined as following: A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.. chemically defined as following: A substance with a defined atomic or molecular structure that results from, or takes part in, reactions involving changes in its structure, composition, or properties.. chromosomes defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.. human defined as following: Members of the species Homo sapiens.. hybrids defined as following: Being comprised of mixed attributes or parts.. centromere defined as following: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.. thymomas defined as following: A neoplasm originating from thymic tissue, usually benign, and frequently encapsulated. Although it is occasionally invasive, metastases are extremely rare. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant. Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin's disease (previously termed granulomatous thymoma), should not be regarded as thymoma. (From Stedman, 25th ed). cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. plasmocytomas defined as following: Any discrete, presumably solitary, mass of neoplastic PLASMA CELLS either in BONE MARROW or various extramedullary sites.. transgenic mice defined as following: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.. murine defined as following: Any of numerous species of small rodents belonging to the genus Mus and various related genera of the family Muridae.. probes defined as following: A device designed to reach into a location for manipulating or sensing..", "label": "yes"}
{"id": "converted_1156", "sentence1": "Is armodafinil used for treatment of insomnia?", "sentence2": " Other therapies, such as sedative hypnotics, target daytime insomnia, while pharmacologic agents such as modafinil, armodafinil, and caffeine and non-pharmacologic approaches such as napping promote nighttime alertness., Other treatment options may include pharmacologic interventions such as modafinil and armodafinil, which have shown efficacy in this population., BACKGROUND: Armodafinil (Nuvigil(®), Cephalon, Inc., Frazer, PA, USA), the longer-lasting isomer of racemic modafinil, is a nonamphetamine, wakefulness-promoting medication. In patients with excessive sleepiness associated with shift work disorder, treated obstructive sleep apnoea, or narcolepsy, armodafinil has been found to improve wakefulness throughout the shift or day. In addition, while not approved for this indication, armodafinil has been found to improve excessive sleepiness associated with jet-lag disorder., STUDY OBJECTIVES: Armodafinil is a wakefulness-promoting medication. Its efficacy and tolerability have been established in 12-week studies of patients with excessive sleepiness (ES) associated with treated obstructive sleep apnea (OSA), shift work disorder (SWD), or narcolepsy. , Armodafinil represents an option for long-term treatment of patients with ES associated with treated OSA, SWD, or narcolepsy., The wakefulness-promoting agents armodafinil and modafinil are FDA approved for the treatment of ES in patients with SWD., CONCLUSIONS: Armodafinil significantly improved overall clinical condition related to excessive sleepiness as rated by the CGI-C and was well tolerated in patients with treated OSA and comorbid depression., CONCLUSION: In patients with excessive sleepiness associated with chronic SWD of moderate or greater severity, armodafinil significantly improved wakefulness during scheduled night work, raising mean nighttime sleep latency above the level considered to indicate severe sleepiness during the daytime. Armodafinil also significantly improved measures of overall clinical condition, long-term memory, and attention. , Adjunct treatment with armodafinil significantly improved wakefulness, long-term memory, and patients' ability to engage in activities of daily living in nCPAP-adherent individuals with ES associated with OSA. , A number of studies have evaluated countermeasures or interventions in shift workers; proposed treatments include chronobiotic interventions, such as light exposure, melatonin, hypnotic agents, caffeine and CNS stimulants (amphetamine), and the wake-promoting agents modafinil and armodafinil. , These studies showed that modafinil and armodafinil significantly improve the ability to sustain wakefulness during waking activities (e.g. working, driving), overall clinical condition, and sustained attention or memory in patients with SWSD. , CONCLUSIONS: In this selected population of patients with OSA/HS and residual ES despite effective treatment with nCPAP, armodafinil QD used as an adjunct to nCPAP treatment was associated with improved wakefulness and overall clinical condition. , Other therapies, such as sedative hypnotics, target daytime insomnia, while pharmacologic agents such as modafinil, armodafinil, and caffeine and non-pharmacologic approaches such as napping promote nighttime alertness., Armodafinil represents an option for long-term treatment of patients with ES associated with treated OSA, SWD, or narcolepsy., Other therapies, such as sedative hypnotics, target daytime insomnia, while pharmacologic agents such as modafinil, armodafinil, and caffeine and non-pharmacologic approaches such as napping promote nighttime alertness., In this selected population of patients with OSA/HS and residual ES despite effective treatment with nCPAP, armodafinil QD used as an adjunct to nCPAP treatment was associated with improved wakefulness and overall clinical condition[SEP]Relations: Armodafinil has relations: contraindication with anxiety disorder, contraindication with anxiety disorder, contraindication with mental disorder, contraindication with mental disorder, drug_drug with Omeprazole, drug_drug with Omeprazole, drug_drug with Antipyrine, drug_drug with Antipyrine, contraindication with neurotic disorder, contraindication with neurotic disorder. Definitions: sleepiness defined as following: Compelling urge to sleep.. 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.. caffeine defined as following: The determination of the amount of caffeine present in a sample.. PA defined as following: A SI derived unit of pressure equivalent to one newton per square meter or 10 bars or to 1.45x10E-4 pounds per square inch.. OSA defined as following: A disorder characterized by recurrent apneas during sleep despite persistent respiratory efforts. It is due to upper airway obstruction. The respiratory pauses may induce HYPERCAPNIA or HYPOXIA. Cardiac arrhythmias and elevation of systemic and pulmonary arterial pressures may occur. Frequent partial arousals occur throughout sleep, resulting in relative SLEEP DEPRIVATION and daytime tiredness. Associated conditions include OBESITY; ACROMEGALY; MYXEDEMA; micrognathia; MYOTONIC DYSTROPHY; adenotonsilar dystrophy; and NEUROMUSCULAR DISEASES. (From Adams et al., Principles of Neurology, 6th ed, p395). Armodafinil defined as following: The R-enantiomer of the racemic synthetic agent modafinil with central nervous system (CNS) stimulant and wakefulness-promoting activities. Although the exact mechanism of action has yet to be fully elucidated, armodafinil appears to inhibit the reuptake of dopamine by binding to the dopamine-reuptake pump, which leads to an increase in extracellular dopamine levels in some brain regions. This agent does not bind to or inhibit several receptors and enzymes that may be involved in sleep/wake regulation and is not a direct- or indirect-acting dopamine receptor agonist. Armodafinil has a longer half-life than modafinil.. modafinil defined as following: A benzhydryl acetamide compound, central nervous system stimulant, and CYP3A4 inducing agent that is used in the treatment of NARCOLEPSY and SLEEP WAKE DISORDERS.. melatonin defined as following: A therapeutic chemically synthesized form of the pineal indole melatonin with antioxidant properties. The pineal synthesis and secretion of melatonin, a serotonin-derived neurohormone, is dependent on beta-adrenergic receptor function. Melatonin is involved in numerous biological functions including circadian rhythm, sleep, the stress response, aging, and immunity.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. armodafinil defined as following: The R-enantiomer of the racemic synthetic agent modafinil with central nervous system (CNS) stimulant and wakefulness-promoting activities. Although the exact mechanism of action has yet to be fully elucidated, armodafinil appears to inhibit the reuptake of dopamine by binding to the dopamine-reuptake pump, which leads to an increase in extracellular dopamine levels in some brain regions. This agent does not bind to or inhibit several receptors and enzymes that may be involved in sleep/wake regulation and is not a direct- or indirect-acting dopamine receptor agonist. Armodafinil has a longer half-life than modafinil.. insomnia defined as following: A sleep disorder characterized by difficulty in falling asleep and/or remaining asleep..", "label": "no"}
{"id": "converted_2459", "sentence1": "Is there any link between ERCC1-XPF and cohesin?", "sentence2": "ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes., Using an in vivo biotinylation tagging approach in mice, we show that the nucleotide excision repair (NER) structure-specific endonuclease ERCC1-XPF complex interacts with the insulator binding protein CTCF, the cohesin subunits SMC1A and SMC3 and with MBD2; the factors co-localize with ATRX at the promoters and control regions (ICRs) of imprinted genes during postnatal hepatic development. Loss of Ercc1 or exposure to MMC triggers the localization of CTCF to heterochromatin, the dissociation of the CTCF-cohesin complex and ATRX from promoters and ICRs, altered histone marks and the aberrant developmental expression of imprinted genes without altering DNA methylation. We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders., Using an in vivo biotinylation tagging approach in mice, we show that the nucleotide excision repair (NER) structure-specific endonuclease ERCC1-XPF complex interacts with the insulator binding protein CTCF, the cohesin subunits SMC1A and SMC3 and with MBD2; the factors co-localize with ATRX at the promoters and control regions (ICRs) of imprinted genes during postnatal hepatic development., We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders., We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders., We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders.
, ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes., We propose that ERCC1-XPF cooperates with CTCF and cohesin to facilitate the developmental silencing of imprinted genes and that persistent DNA damage triggers chromatin changes that affect gene expression programs associated with NER disorders..[SEP]Relations: heterochromatin has relations: cellcomp_protein with HSF1, cellcomp_protein with HSF1, cellcomp_protein with FOXC1, cellcomp_protein with FOXC1, cellcomp_protein with MORC2, cellcomp_protein with MORC2, cellcomp_protein with ORC2, cellcomp_protein with ORC2, cellcomp_protein with CBX1, cellcomp_protein with CBX1. Definitions: ATRX defined as following: A rare, X-linked recessive inherited syndrome caused by mutations in the ATRX gene. It is characterized by intellectual disability, developmental delays, hypotonia, widely spaced eyes, small nose, low-set ears, tented upper lip, skeletal abnormalities, and a mild form of alpha thalassemia.. CTCF defined as following: CCN family member 2 (349 aa, ~38kDa) is encoded by the human CCN2 gene. This protein plays a role in the promotion of proliferation and differentiation of chondrocytes and also mediates heparin- and divalent cation-dependent cell adhesion in many different cell types.. SMC3 defined as following: Human SMC3 wild-type allele is located in the vicinity of 10q25 and is approximately 37 kb in length. This allele, which encodes structural maintenance of chromosomes protein 3, is involved in the regulation of chromosome migration during mitosis.. promoters defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. Ercc1 defined as following: DNA excision repair protein ERCC-1 (297 aa, ~33 kDa) is encoded by the human ERCC1 gene. This protein plays a role in 5-prime incision during both UV cross-link repair and nucleotide excision repair.. heterochromatin defined as following: The portion of chromosome material that remains condensed and is transcriptionally inactive during INTERPHASE.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. MMC defined as following: An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"}
{"id": "converted_865", "sentence1": "Have C12orf65 mutations been associated with axonal neuropathy and optic atrophy?", "sentence2": "Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy, Charcot-Marie Tooth disease (CMT) forms a clinically and genetically heterogeneous group of disorders. Although a number of disease genes have been identified for CMT, the gene discovery for some complex form of CMT has lagged behind. The association of neuropathy and optic atrophy (also known as CMT type 6) has been described with autosomaldominant, recessive and X-linked modes of inheritance. Mutations in Mitofusin 2 have been found to cause dominant forms of CMT6. Phosphoribosylpyrophosphate synthetase-I mutations cause X-linked CMT6, but until now, mutations in the recessive forms of disease have never been identified.METHODS: We here describe a family with three affected individuals who inherited in an autosomal recessive fashion a childhood onset neuropathy and optic atrophy. Using homozygosity mapping in the family and exome sequencing in two affected individuals we identified a novel protein-truncating mutation in the C12orf65 gene, which encodes for a protein involved in mitochondrial translation, Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy., Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features., C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families., A homozygous mutation of C12orf65 causes spastic paraplegia with optic atrophy and neuropathy (SPG55)., Optic atrophy and a Leigh-like syndrome due to mutations in the c12orf65 gene: report of a novel mutation and review of the literature., Recently, we identified the causative gene, C12orf65, that was reported the gene for Leigh syndrome, for autosomal recessive spastic paraplegia with optic atrophy and neuropathy (SPG55)., We describe 2 siblings with compound heterozygous mutations in the recently identified C12orf65 gene who presented with optic atrophy and mild developmental delays and subsequently developed bilateral, symmetric lesions in the brainstem reminiscent of Leigh syndrome., C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families, Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features, CONCLUSIONS: This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy., C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families. , Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features. , We described a large consanguineous family with neuropathy and optic atrophy carrying a loss of function mutation in the C12orf65 gene., In these patients, we identified a homozygous splice mutation, g.21043 T>A (c.282+2 T>A) which leads to skipping of exon 2. Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features., This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy., Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features., Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy., This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy., A homozygous mutation of C12orf65 causes spastic paraplegia with optic atrophy and neuropathy (SPG55)., C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families.[SEP]Relations: Optic atrophy has relations: disease_phenotype_positive with neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, disease_phenotype_positive with neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, disease_phenotype_positive with cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome, disease_phenotype_positive with cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome, disease_phenotype_positive with mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency, disease_phenotype_positive with mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency, disease_phenotype_positive with neurodevelopmental disorder with visual defects and brain anomalies, disease_phenotype_positive with neurodevelopmental disorder with visual defects and brain anomalies, disease_phenotype_positive with Mowat-Wilson syndrome due to a ZEB2 point mutation, disease_phenotype_positive with Mowat-Wilson syndrome due to a ZEB2 point mutation. Definitions: gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. CMT6 defined as following: A rare axonal hereditary motor and sensory neuropathy disease characterized by progressive, peripheral, axonal sensorimotor neuropathy (of variable severity), affecting predominantly the distal lower limbs, associated with progressive, variably severe, optic atrophy, which frequently leads to visual loss. Patients typically present distal limb muscle weakness and atrophy, hypo/areflexia, foot deformities, poor visual acuity (often with a central scotoma), nystagmus, and reduced peripheral and nocturnal vision. Additional reported manifestations include sensorineural hearing loss, major joint contractures, anosmia, scoliosis/lumbar hyperlordosis, cognitive impairment and vocal cord paresis.. Mitofusin 2 defined as following: This gene is involved in mitochondrial fusion.. peripheral neuropathy defined as following: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.. 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.. axonal neuropathy defined as following: Any nerve disorder affecting the axon of a nerve.. 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.. CMT defined as following: brand name of choline magnesium trisalicylate. Leigh syndrome defined as following: A group of metabolic disorders primarily of infancy characterized by the subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, dysphagia, and lactic acidosis. Pathological features include spongy degeneration of the neuropile of the basal ganglia, thalamus, brain stem, and spinal cord. Patterns of inheritance include X-linked recessive, autosomal recessive, and mitochondrial. Leigh disease has been associated with mutations in genes for the PYRUVATE DEHYDROGENASE COMPLEX; CYTOCHROME-C OXIDASE; ATP synthase subunit 6; and subunits of mitochondrial complex I. (From Menkes, Textbook of Child Neurology, 5th ed, p850).. optic atrophy defined as following: Dominant optic atrophy is a hereditary optic neuropathy causing decreased visual acuity, color vision deficits, a centrocecal scotoma, and optic nerve pallor (Hum. Genet. 1998; 102: 79-86). Mutations leading to this condition have been mapped to the OPA1 gene at chromosome 3q28-q29. OPA1 codes for a dynamin-related GTPase that localizes to mitochondria.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. mitochondrial dysfunction defined as following: A functional anomaly of mitochondria. [ORCID:0000-0001-5208-3432]. spastic paraparesis defined as following: Mild or moderate loss of motor function accompanied by spasticity in the lower extremities. This condition is a manifestation of CENTRAL NERVOUS SYSTEM DISEASES that cause injury to the motor cortex or descending motor pathways.. neuropathy defined as following: A disorder affecting the cranial nerves or the peripheral nervous system. It manifests with pain, tingling, numbness, and muscle weakness. It may be the result of physical injury, toxic substances, viral diseases, diabetes, renal failure, cancer, and drugs.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"}
{"id": "converted_1501", "sentence1": "Have germline variants been associated to colorectal cancer?", "sentence2": "Overall, we identified aberrant transcripts in 8% of the patients (familial cases 30%; early-onset manifestation 21%). In eight of them, two different out-of-frame pseudoexons were found consisting of a 167-bp insertion from intron 4 in five families with a shared founder haplotype and a 83-bp insertion from intron 10 in three patients. The pseudoexon formation was caused by three different heterozygous germline mutations, which are supposed to activate cryptic splice sites, We apply OS-Seq to resequence the exons of either 10 or 344 cancer genes from human DNA samples. In our assessment of capture performance, >87% of the captured sequence originated from the intended target region with sequencing coverage falling within a tenfold range for a majority of all targets. Single nucleotide variants (SNVs) called from OS-Seq data agreed with >95% of variants obtained from whole-genome sequencing of the same individual., The minor alleles of CD44 rs8193 C>T, ALCAM rs1157 G>A, and LGR5 rs17109924 T>C were significantly associated with increased TTR (9.4 vs. 5.4 years; HR, 0.51; 95% CI: 0.35-0.93; P = 0.022; 11.3 vs. 5.7 years; HR, 0.56; 95% CI: 0.33-0.94; P = 0.024, and 10.7 vs. 5.7 years; HR, 0.33; 95% CI: 0.12-0.90; P = 0.023, respectively) and remained significant in the multivariate analysis stratified by ethnicity. In recursive partitioning, a specific gene variant profile including LGR5 rs17109924, CD44 rs8193, and ALDH1A1 rs1342024 represented a high-risk subgroup with a median TTR of 1.7 years (HR, 6.71, 95% CI: 2.71-16.63, P < 0.001)., In this study, we identified common germline variants in VEGF-dependent and -independent angiogenesis genes predicting clinical outcome and tumor response in patients with mCRC receiving first-line bevacizumab and oxaliplatin-based chemotherapy., We identified 22 nonsynonymous somatic mutations of which the majority was of missense type. In germline, three novel nonsynonymous variants were identified in the following genes: CSMD3, EPHB6 and C10orf137, and none of the variants were present in 890 population-matched healthy controls. It is possible that the identified germline variants modulate predisposition to CRC., One patient proved to carry an APC whole-gene deletion; 4 of 25 (16%) patients showed biallelic and 3 of 25 (12%) monoallelic MUTYH mutations. In the three heterozygous subjects no pathogenetic variants were found in OGG1, MTH1, APE1, MSH2, and MSH6 genes. Frequency assessment of MUTYH mutations in healthy subjects showed that only Y165C and G382D reach a subpolymorphic frequency., Scrutinizing the molecular genetic results and family data of 242 index patients with pathogenic APC mutations led to the identification of 10 mosaic cases (4%). C>T transitions were observed in CGA sites in four of the 10 cases with somatic mosaicism, which is significantly more than 26 of the 232 non-mosaic cases (p = 0.02). Phenotypes of patients with somatic mosaicism ranged from an attenuated form of polyposis coli to florid polyposis with major extracolonic manifestations., Altogether 12 previously reported changes and four novel genetic alterations, mostly in intronic sequences, were identified. The results revealed the presence of biallelic germline MYH mutations in two patients. These patients were compound heterozygotes for two of the most common germline mutations c.494 A>G (p.Y165C); c.1,145 G>A (p.G382D). These variants are established to be associated with adenomatous polyposis and colorectal cancer.[SEP]Relations: EDRF1 has relations: disease_protein with colorectal cancer, disease_protein with colorectal cancer, disease_protein with colorectal carcinoma, disease_protein with colorectal carcinoma. Somatic mutation has relations: disease_phenotype_positive with colorectal cancer, disease_phenotype_positive with colorectal cancer, disease_phenotype_positive with esophageal cancer, disease_phenotype_positive with esophageal cancer. malignant colon neoplasm has relations: disease_disease with colorectal cancer, disease_disease with colorectal cancer. Definitions: MSH2 defined as following: DNA mismatch repair protein Msh2 (934 aa, ~105 kDa) is encoded by the human MSH2 gene. This protein is involved in DNA mismatch repair.. gene variant defined as following: A variation in the nucleic acid sequence of a specific gene.. TTR defined as following: Transthyretin (147 aa, ~16 kDa) is encoded by the human TTR gene. This protein is involved in both the binding and transport of retinol and thyroxine.. somatic mosaicism defined as following: The presence of genetically distinct populations of somatic cells in a given organism caused by DNA mutations, epigenetic alterations of DNA, chromosomal abnormalities or the spontaneous reversion of inherited mutations. [HPO:probinson, PMID:12360233]. CRC defined as following: The disappearance of all signs of cancer, including the absence of a detectable disease-related genetic abnormality, as determined by techniques such as karyotyping or FISH, in response to treatment.. MUTYH defined as following: Adenine DNA glycosylase protein (546 aa, ~60 kDa) is encoded by the MUTYH gene. This nuclear enzyme plays a role in mismatch repair via the removal of mutagenic adenine/8-oxo-guanine.. MTH1 defined as following: Human NUDT1 wild-type allele is located within 7p22 and is approximately 9 kb in length. This allele, which encodes 7,8-dihydro-8-oxoguanine triphosphatase protein, is involved in the hydrolysis of 8-oxo-dGTP in the free nucleotide pool. Overexpression of the NUDT1 gene is associated with several types of cancer such as non-small-cell lung carcinomas, renal cell carcinomas and prostate cancer.. OGG1 defined as following: N-glycosylase/DNA lyase (345 aa, ~39 kDa) is encoded by the human OGG1 gene. This protein is involved in nucleotide excision repair.. transcripts defined as following: The initial RNA molecule produced by transcription.. MYH defined as following: Human MUTYH allele is located within 1p34.3-p32.1 and is approximately 92 kb in length. This allele, which encodes adenine DNA glycosylase protein, is involved in repair of the mutagenic adenosine/8-oxo-guanine mismatched base pair in DNA. Certain allelic variants of the MUTYH gene are associated with colorectal cancer.. APC defined as following: A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.. CSMD3 defined as following: CUB and sushi domain-containing protein 3 (3707 aa, ~406 kDa) is encoded by the human CSMD3 gene. This protein plays a role in the development of neuronal projections.. APE1 defined as following: This gene is involved in DNA repair processes.. 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.. LGR5 defined as following: Leucine-rich repeat-containing G-protein coupled receptor 5 (907 aa, ~100 kDa) is encoded by the human LGR5 gene. This protein plays a role in signal transduction.. exons defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.. adenomatous polyposis defined as following: A polyposis syndrome due to an autosomal dominant mutation of the APC genes (GENES, APC) on CHROMOSOME 5. The syndrome is characterized by the development of hundreds of ADENOMATOUS POLYPS in the COLON and RECTUM of affected individuals by early adulthood.. 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.. polyposis defined as following: A condition characterized by the presence of numerous polyps.. MSH6 defined as following: DNA mismatch repair protein Msh6 (1360 aa, ~153 kDa) is encoded by the human MSH6 gene. This protein is involved in the DNA damage response.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. HR defined as following: The rapid, localized death of plant cells in response to invasion by a pathogen. [ISBN:0582227089]. variants defined as following: An alteration or difference from a norm or standard.. EPHB6 defined as following: Ephrin type-B receptor 6 (1021 aa, ~111 kDa) is encoded by the human EPHB6 gene. This protein plays a role in the regulation of ephrin-B signaling pathways.. genetic alterations defined as following: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations..", "label": "yes"}
{"id": "converted_231", "sentence1": "Do orphan and gene related CpG islands follow power-law-like distributions?", "sentence2": "Orphan and gene related CpG Islands follow power-law-like distributions in several genomes: evidence of function-related and taxonomy-related modes of distribution., Here, an investigation of their distributional characteristics in a variety of genomes is undertaken for both whole CGI populations as well as for CGI subsets that lie away from known genes (gene-unrelated or \"orphan\" CGIs). In both cases power-law-like linearity in double logarithmic scale is found., Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow. The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model., Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow., The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model., Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow. , Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow. The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model., Initially, they were assigned the role of transcriptional regulation of protein-coding genes, especially the house-keeping ones, while more recently there is found evidence that they are involved in several other functions as well, which might include regulation of the expression of RNA genes, DNA replication etc. Here, an investigation of their distributional characteristics in a variety of genomes is undertaken for both whole CGI populations as well as for CGI subsets that lie away from known genes (gene-unrelated or \"orphan\" CGIs). In both cases power-law-like linearity in double logarithmic scale is found. , Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow., The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model., Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow.[SEP]Definitions: gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"}
{"id": "converted_3337", "sentence1": "Are Spinal Intradural Primary Malignant Peripheral Nerve Sheath Tumors(MPNST) rare in neurofibromatosis patients?", "sentence2": "Spinal intradural primary malignant peripheral nerve sheath tumors (MPNST) are rare in patients without neurofibromatosis., Primary malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare in patients without a history of neurofibromatosis; only 18 cases have been reported in the English-language literature to this point.[SEP]Relations: malignant peripheral nerve sheath tumor has relations: disease_disease with tumor of cranial and spinal nerves, disease_disease with tumor of cranial and spinal nerves, disease_disease with peripheral nervous system cancer, disease_disease with peripheral nervous system cancer, disease_disease with nerve sheath neoplasm, disease_disease with nerve sheath neoplasm, disease_disease with malignant melanocytic neoplasm of the peripheral nerve sheath, disease_disease with malignant melanocytic neoplasm of the peripheral nerve sheath, disease_disease with malignant glandular tumor of peripheral nerve sheath, disease_disease with malignant glandular tumor of peripheral nerve sheath. Definitions: MPNST defined as following: A malignant neurilemmoma with nerve sheath differentiation. It is often associated with NEUROFIBROMATOSIS 1 and RHABDOMYOSARCOMA.. neurofibromatosis defined as following: Tumor suppressor genes located on the long arm of human chromosome 17 in the region 17q11.2. Mutation of these genes is thought to cause NEUROFIBROMATOSIS 1, Watson syndrome, and LEOPARD syndrome..", "label": "no"}
{"id": "converted_3408", "sentence1": "Is cathepsin L active in endosomes?", "sentence2": "Cathepsin L in the Late Endosome/Lysosome, endosomal cathepsin L, Immunofluorescence and immunoblotting investigations revealed the presence of cathepsin L in the nuclear compartment in addition to its expected endo-lysosomal localization in colorectal carcinoma cells., cleavage by the endosomal/lysosomal protease cathepsin L[SEP]Definitions: endosomes defined as following: Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface..", "label": "yes"}
{"id": "converted_137", "sentence1": "Is GAGA associated with nucleosome-free regions (NFR)?", "sentence2": "One of the three nuclease hypersensitive sites in the Fab-7 boundary, HS1, contains multiple consensus-binding sequences for the GAGA factor, a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin., The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1., The interactions of GAGA factor and heat shock factor with their binding sites in chromatin occurred in two modes. Their interaction with binding sites in the nucleosome-free regions did not require ATP. In the presence of ATP both factors interacted also with nucleosomal binding sites, causing nucleosome rearrangements and a refinement of nucleosome positions, While chromatin remodeling upon transcription factor interaction has previously been interpreted to involve nucleosome disruption, the data suggest energy-dependent nucleosome sliding as main principle of chromatin reorganization., These (CT)n repeats are associated with a nonhistone protein(s) in vivo and are bound by a purified Drosophila protein, the GAGA factor, in vitro., This (CT)n element appears to contribute to formation of the wild-type chromatin structure of hsp26, an organized nucleosome array that leaves the HSEs in nucleosome-free, DNase I-hypersensitive (DH) site, The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1., One of the three nuclease hypersensitive sites in the Fab-7 boundary, HS1, contains multiple consensus-binding sequences for the GAGA factor, a protein known to be involved in the formation and/or maintenance of nucleosome-free regions of chromatin., The iab-7 polycomb response element maps to a nucleosome-free region of chromatin and requires both GAGA and pleiohomeotic for silencing activity., The HS3 sequence contains consensus binding sites for the GAGA factor, a protein implicated in the formation of nucleosome-free regions of chromatin, and Pleiohomeotic (Pho), a Polycomb group protein that is related to the mammalian transcription factor YY1. [SEP]Relations: nucleosome mobilization has relations: bioprocess_protein with POLE3, bioprocess_protein with POLE3, bioprocess_bioprocess with nucleosome organization, bioprocess_bioprocess with nucleosome organization, bioprocess_protein with INO80, bioprocess_protein with INO80, bioprocess_protein with ARID1A, bioprocess_protein with ARID1A, bioprocess_protein with BPTF, bioprocess_protein with BPTF. Definitions: leaves defined as following: Expanded structures, usually green, of vascular plants, characteristically consisting of a bladelike expansion attached to a stem, and functioning as the principal organ of photosynthesis and transpiration. (American Heritage Dictionary, 2d ed). Pho defined as following: A condition chiefly characterized by thickening of the skin of the head and distal extremities, deep folds and furrows of the skin of the forehead, cheeks, and scalp, SEBORRHEA; HYPERHIDROSIS; periostosis of the long bones, digital clubbing, and spadelike enlargement of the hands and feet. It is more prevalent in the male, and is usually first evident during adolescence. Inheritance is primarily autosomal recessive, but an autosomal dominant form exists.. binding sites defined as following: The parts of a macromolecule that directly participate in its specific combination with another molecule.. transcription factor defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. Polycomb group protein defined as following: A family of proteins that play a role in CHROMATIN REMODELING. They are best known for silencing HOX GENES and the regulation of EPIGENETIC PROCESSES.. YY1 defined as following: This gene is involved in the negative regulation of transcription.. HS1 defined as following: Human EEF1A2 wild-type allele is located in the vicinity of 20q13.3 and is approximately 11 kb in length. This allele, which encodes elongation factor 1-alpha 2 protein, is involved in the promotion of protein elongation. The gene is expressed aberrantly at elevated levels in many ovarian cancers.. nucleosome defined as following: A complex comprised of DNA wound around a multisubunit core and associated proteins, which forms the primary packing unit of DNA into higher order structures. [GOC:elh]. ATP defined as following: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.. protein defined as following: Protein; provides access to the encoding gene via its GenBank Accession, the taxon in which this instance of the protein occurs, and references to homologous proteins in other species.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. mammalian defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. NFR defined as following: The quotient of the number of particular entities (constituents) and the number of all constituents in the system..", "label": "yes"}
{"id": "converted_3151", "sentence1": "Can oleuropein aglycone interfere with amyloid aggregation?", "sentence2": "Oleuropein, a phenolic secoiroid glycoside, is the main polyphenol in the olive oil. It has been reported that the aglycone form of Oleuropein (OleA) interferes in vitro and in vivo with amyloid aggregation of a number of proteins/peptides involved in amyloid, particularly neurodegenerative, diseases avoiding the growth of toxic oligomers and displaying protection against cognitive deterioration.[SEP]Relations: Abnormality of immune serum protein physiology has relations: phenotype_phenotype with Abnormal cytokine signaling, phenotype_phenotype with Abnormal cytokine signaling. Motor deterioration has relations: disease_phenotype_positive with PRKAR1B-related neurodegenerative dementia with intermediate filaments, disease_phenotype_positive with PRKAR1B-related neurodegenerative dementia with intermediate filaments, disease_phenotype_positive with neuronal ceroid lipofuscinosis, disease_phenotype_positive with neuronal ceroid lipofuscinosis, disease_phenotype_positive with infantile neuronal ceroid lipofuscinosis, disease_phenotype_positive with infantile neuronal ceroid lipofuscinosis, disease_phenotype_positive with spinocerebellar ataxia, disease_phenotype_positive with spinocerebellar ataxia. Definitions: polyphenol defined as following: A large class of organic compounds having more than one PHENOL group.. OleA defined as following: A plant genus of the family Oleaceae. The olive fruit is the source of OLIVE OIL.. amyloid defined as following: A family of apolipoproteins that are associated with high-density lipoprotein particles in the serum. These proteins may play a role in both the acute-phase of inflammation and in cholesterol transport..", "label": "yes"}
{"id": "converted_4065", "sentence1": "Is ofatumumab effective for multiple sclerosis?", "sentence2": "Anti-CD20 Agents for Multiple Sclerosis: Spotlight on Ocrelizumab and Ofatumumab., Ofatumumab, a fully human anti-CD20 monoclonal antibody, that binds a distinct epitope, has been further investigated in phase 3 trials for relapsing forms of MS. , Conclusion: Ofatumumab offers beneficial outcomes for RMS by reducing relapse and disability progression risk., Currently, new therapies are emerging that promise more convenience and an improved safety profile (ofatumumab) or remyelinating potential with clinical improvement (opicinumab)., The emerging B-cell depleting therapies, particularly anti-CD20 agents such as rituximab, ocrelizumab, as well as the fully human ofatumumab, have shown promising clinical and magnetic resonance imaging benefit., AREAS COVERED: In this manuscript, we review mechanisms of action, efficacy, safety, and tolerance of anti-CD20 therapies for MS, including rituximab, ocrelizumab, and ofatumumab., Another CD20 directed mAb, ofatumumab, is in phase 3. , Ofatumumab offers beneficial outcomes for RMS by reducing relapse and disability progression risk., CONCLUSION: Imaging showed that all subcutaneous ofatumumab doses demonstrated efficacy (most robust: cumulative doses ≥30 mg/12 wk), with a safety profile consistent with existing ofatumumab data., CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. [SEP]Relations: Ofatumumab has relations: drug_drug with Denosumab, drug_drug with Denosumab, drug_drug with Crotedumab, drug_drug with Crotedumab, drug_drug with Urelumab, drug_drug with Urelumab, drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Fasinumab, drug_drug with Fasinumab. Definitions: ocrelizumab defined as following: A Fc-modified, humanized monoclonal antibody directed against the B-cell CD20 cell surface antigen, with immunosuppressive activity. Ocrelizumab binds to CD20 on the surfaces of B-cells, triggering complement-dependent cell lysis (CDCL) and antibody-dependent cell-mediated cytotoxicity (ADCC) of B-cells overexpressing CD20. The CD20 antigen, a non-glycosylated cell surface phosphoprotein that acts as a calcium ion channel, is found on over 90% of B-cells, B-cell lymphomas, and other lymphoid tumor cells of B-cell origin; it plays an important role in B-cell functioning.. ofatumumab defined as following: A fully human, high-affinity IgG1 monoclonal antibody directed against the B cell CD20 cell surface antigen with potential antineoplastic activity. Ofatumumab binds specifically to CD20 on the surfaces of B cells, triggering complement-dependent cell lysis (CDCL) and antibody-dependent cell-mediated cytotoxicity (ADCC) of B cells overexpressing CD20. The CD20 antigen, found on over 90% of B cells, B cell lymphomas, and other B cells of lymphoid tumors of B cell origin, is a non-glycosylated cell surface phosphoprotein that acts as a calcium ion channel; it is exclusively expressed on B cells during most stages of B cell development.. CD20 defined as following: Human MS4A1 wild-type allele is located within 11q12 and is approximately 13 kb in length. This allele, which encodes B-lymphocyte antigen CD20 protein, plays a role in the development and differentiation of B-cells into plasma cells.. human defined as following: Members of the species Homo sapiens.. 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.. 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). RMS defined as following: A statistical measure of the magnitude of a set of variable values. The root mean square is the square root of the mean value for the squares of the original values..", "label": "yes"}
{"id": "converted_3711", "sentence1": "Was vivotif licensed in Europe and the US at the same time?", "sentence2": "Vivotif® is an oral live attenuated vaccine which contains a mutated strain of Salmonella (Ty21a) and reproduces the natural infection. The vaccine was first licensed in Europe in 1983 and in the US in 1989, and over the years it has proved efficacious and safe.[SEP]Relations: salmonellosis has relations: disease_protein with HLA-DRB1, disease_protein with HLA-DRB1, disease_disease with invasive non-typhoidal salmonellosis, disease_disease with invasive non-typhoidal salmonellosis, disease_disease with paratyphoid fever, disease_disease with paratyphoid fever, disease_disease with salmonella infections, animal, disease_disease with salmonella infections, animal, disease_disease with typhoid fever, disease_disease with typhoid fever. Definitions: Salmonella defined as following: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility..", "label": "no"}
{"id": "converted_3996", "sentence1": "Are mucin overexpression associated with disease?", "sentence2": "The pathological mechanism underlying hepatolithiasis is closely related to bacterial infections of the intrahepatic bile duct, followed by chronic inflammation and the overexpression of mucin 5AC (MUC5AC)., MUC1 is a membrane glycoprotein, which in adenocarninomas is overexpressed and exhibits truncated O-glycosylation. , Mucin 13 (MUC13) is reportedly overexpressed in human malignancies., Inflammation causes MUC1 overexpression and hypoglycosylation. [SEP]Relations: Protein S human has relations: drug_drug with Mitomycin, drug_drug with Mitomycin, drug_drug with Mitomycin, drug_drug with Mitomycin, drug_drug with Obinutuzumab, drug_drug with Obinutuzumab, drug_drug with Obinutuzumab, drug_drug with Obinutuzumab. bladder calculus has relations: disease_disease with urinary bladder disease, disease_disease with urinary bladder disease. Definitions: MUC1 defined as following: Human MUC1 wild-type allele is located within 1q21 and is approximately 121 kb in length. This allele, which encodes mucin-like protein 1, plays a role in both cellular defense by binding pathogens and in cell signaling.. mucin defined as following: Mucin-1 (1255 aa, ~122 kDa) is encoded by the human MUC1 gene. This protein plays a role in both signaling and cell adhesion.. human defined as following: Members of the species Homo sapiens.. membrane glycoprotein defined as following: Glycoproteins found on the membrane or surface of cells.. MUC5AC defined as following: Mucin-5AC (5030 aa, ~527 kDa) is encoded by the human MUC5AC gene. This protein plays a role in the defense of the gastrointestinal and respiratory tracts from microorganism infection.. intrahepatic bile duct defined as following: Passages within the liver for the conveyance of bile. Includes right and left hepatic ducts even though these may join outside the liver to form the common hepatic duct.. hepatolithiasis defined as following: The presence of solitary or multiple stones in the intrahepatic bile ducts.. disease defined as following: A definite pathologic process with a characteristic set of signs and symptoms. It may affect the whole body or any of its parts, and its etiology, pathology, and prognosis may be known or unknown..", "label": "yes"}
{"id": "converted_1139", "sentence1": "Are ACTA1 (alpha actin) and NEB (nebulin) genes related to nemaline myopathy?", "sentence2": "Nemaline myopathy (NM) is a group of congenital myopathies, characterized by the presence of distinct rod-like inclusions \"nemaline bodies\" in the sarcoplasm of skeletal muscle fibers. To date, ACTA1, NEB, TPM3, TPM2, TNNT1, and CFL2 have been found to cause NM., Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin). 20-25% of NM cases carry ACTA1 defects and these particular mutations usually induce substitutions of single residues in the actin protein. , Nemaline myopathy (NM) is a genetically and clinically heterogenous muscle disorder, which is myopathologically characterized by nemaline bodies. Mutations in six genes have been reported to cause NM: Nebulin (NEB Pelin 1999), alpha-skeletal muscle actin (ACTA1 Nowak 1999), alpha-slow tropomyosin (TPM3 Laing 1995), beta-tropomyosin (TPM2 Donner 2002), slow troponin T (TNNT1 Johnston 2000) and cofilin 2 (CFL2 Agrawal 2007). The majority of cases are due to mutation in NEB and ACTA1. , Nemaline myopathy is a heterogenous form of congenital myopathy characterised by a variable spectrum of clinical features, predominated in the severe form by profound muscle hypotonia and weakness accompanied by respiratory insufficiency. The clinical variability, with differing age of onset and severity of symptoms makes the diagnosis of nemaline myopathy difficult in some cases. Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle. , Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes. , We report muscle MRI findings of 10 patients from 8 families with nemaline myopathy. Patients with involvement of the nebulin (NEB) gene showed a consistent pattern of selective muscle involvement corresponding to clinical severity., Patients with nemaline myopathy secondary to mutations in the skeletal muscle alpha-actin (ACTA1) gene showed diffuse involvement of thigh and leg muscles with relative sparing of the gastrocnemii., Congenital myopathies are clinical and genetic heterogeneous disorders characterized by skeletal muscle weakness ranging in severity. Three major forms have been identified: actin myopathy, intranuclear rod myopathy, and nemaline myopathy. Nemaline myopathy is the most common of these myopathies and is further subdivided into seven groups according to severity, progressiveness, and age of onset. At present, five genes have been linked to congenital myopathies. These include alpha-actin (ACTA1), alpha- and beta-tropomyosin (TPM3 and TPM2), troponin T (TNNT1), and nebulin (NEB). , Nemaline myopathy is a structural congenital myopathy which may show both autosomal dominant and autosomal recessive inheritance patterns. Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42., Nemaline myopathy is a clinically and genetically heterogeneous condition. The clinical spectrum ranges from severe cases with antenatal or neonatal onset and early death to late onset cases with only slow progression. Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42. , Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin)., Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42., Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1)., Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes., Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle., Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1)., Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42., Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42., Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes, Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1), Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42, Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin), Five genes have now been associated with nemaline myopathy: alpha-tropomyosin-3 (TPM3), alpha-actin (ACTA1), nebulin (NEB), beta-tropomysin (TPM2) and troponin T (TNNT1), Nemaline myopathy (NM) is the most common congenital myopathy and is caused by mutations in various genes including NEB (nebulin), TPM2 (beta-tropomyosin), TPM3 (gamma-tropomyosin), and ACTA1 (skeletal alpha-actin), Mutations in three different genes have been identified as the cause of nemaline myopathy: the gene for slow alpha-tropomyosin 3 (TPM3) at 1q22-23, the nebulin gene (NEB) at 2q21.1-q22, and the actin gene (ACTA1) at 1q42, Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42, Most nemaline myopathy patients have mutations in the nebulin (NEB) or skeletal muscle alpha-actin (ACTA1) genes, Severe forms of nemaline myopathy may be caused by mutation of a number of different genes: skeletal muscle actin (ACTA1), nebulin (NEB) and alpha-tropomyosin (TPM3), all of which encode components of the sarcomeric thin filaments of skeletal muscle[SEP]Relations: nemaline myopathy has relations: disease_protein with ACTA1, disease_protein with ACTA1, disease_disease with alpha-actinopathy, disease_disease with alpha-actinopathy, disease_protein with NEB, disease_protein with NEB, disease_disease with qualitative or quantitative defects of alpha-actin, disease_disease with qualitative or quantitative defects of alpha-actin. alpha-actinopathy has relations: disease_disease with nemaline myopathy, disease_disease with nemaline myopathy. Definitions: troponin T defined as following: The determination of the amount of troponin T present in a blood sample.. chromosome defined as following: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.. weakness defined as following: Clinical sign or symptom manifested as debility, or lack or loss of strength and energy.. TPM3 defined as following: Tropomyosin alpha-3 chain (284 aa, ~33 kDa) is encoded by the human TPM3 gene. This protein plays a role in the modulation of muscle contraction.. cofilin 2 defined as following: A member of the cofilin family of proteins that is expressed in MUSCLE CELLS. It has ACTIN depolymerization activity that is dependent on HYDROGEN-ION CONCENTRATION.. muscle hypotonia defined as following: A diminution of the skeletal muscle tone marked by a diminished resistance to passive stretching.. muscle defined as following: Contractile tissue that produces movement in animals.. NM defined as following: A group of inherited congenital myopathic conditions characterized clinically by weakness, hypotonia, and prominent hypoplasia of proximal muscles including the face. Muscle biopsy reveals large numbers of rod-shaped structures beneath the muscle fiber plasma membrane. This disorder is genetically heterogeneous and may occasionally present in adults. (Adams et al., Principles of Neurology, 6th ed, p1453). genetic defined as following: Having to do with information that is passed from parents to offspring through genes in sperm and egg cells.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. alpha-tropomyosin defined as following: Tropomyosin alpha-1 chain (284 aa, ~33 kDa) is encoded by the human TPM1 gene. This protein plays a role in muscle contraction.. sarcoplasm defined as following: The cytoplasm of a muscle cell; includes the sarcoplasmic reticulum. [ISBN:0198547684]. 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.. TPM2 defined as following: This gene plays a role in both muscle contraction and actin binding.. myopathies defined as following: Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.. NEB defined as following: The mitotic cell cycle process in which the controlled partial or complete breakdown of the nuclear membranes during occurs during mitosis. [GOC:bf, PMID:32848252]. autosomal dominant defined as following: A rare distal arthrogryposis syndrome with characteristics of multiple pterygia (typically involving the neck, axilla and popliteal areas), joint contractures, ptosis, camptodactyly of the hands with hypoplastic flexion creases, vertebral fusions, severe scoliosis and short stature. There is evidence this disease is caused by heterozygous mutation in the MYH3 gene on chromosome 17p13.. respiratory insufficiency defined as following: Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed). nemaline myopathy defined as following: A type of nemaline myopathy (NM) only observed in several families of the Amish community.. 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.. 1q42 defined as following: A chromosome band present on 1q.", "label": "yes"}
{"id": "converted_3237", "sentence1": "Is the crystal structure of Pim-1 available?", "sentence2": "Recent crystallographic studies of Pim-1 have identified unique structural features but have not provided insight into how the kinase recognizes its target substrates. , a co-crystal structure of lead molecule (HS38) in complex with DAPK3, a dual Pim/DAPK3 inhibitor (HS56), The crystal structure of this compound with PIM1 confirmed the predicted binding mode and protein-ligand interactions except those in the acidic ribose pocket. , Using the determined X-ray crystal structure of PIM1 complexed to the compound 1-R as a control, we discuss the importance of including the protein flexibility inherent in the ensemble docking protocol, for the accuracy of the structure prediction of the bound state. , Here, we describe the crystal structure of Pim1 in complex with a newly developed pyrido[4,3-d]pyrimidine-derivative inhibitor (SKI-O-068)., Crystallographic and docking data analyses have been undertaken using inhibitor complexes , The crystal structures of Pim1 in apo form and bound with AMPPNP have been solved[SEP]Relations: Protein C has relations: drug_drug with Pivhydrazine, drug_drug with Pivhydrazine, drug_drug with Peginterferon beta-1a, drug_drug with Peginterferon beta-1a, drug_drug with Piroxicam, drug_drug with Piroxicam, drug_drug with Pirlindole, drug_drug with Pirlindole, drug_drug with Peginterferon alfa-2b, drug_drug with Peginterferon alfa-2b. Definitions: AMPPNP defined as following: 5'-Adenylic acid, monoanhydride with imidodiphosphoric acid. An analog of ATP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It is a potent competitive inhibitor of soluble and membrane-bound mitochondrial ATPase and also inhibits ATP-dependent reactions of oxidative phosphorylation.. 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.. kinase defined as following: Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs)..", "label": "yes"}
{"id": "converted_2936", "sentence1": "Can midostaurin inhibit angiogenesis?", "sentence2": "Midostaurin was a prototype kinase inhibitor, originally developed as a protein kinase C inhibitor and subsequently as an angiogenesis inhibitor, based on its inhibition of vascular endothelial growth factor receptor.[SEP]Relations: Midostaurin has relations: drug_drug with Estradiol, drug_drug with Estradiol, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Aldosterone, drug_drug with Aldosterone, drug_drug with Sparteine, drug_drug with Sparteine, drug_drug with Azelastine, drug_drug with Azelastine. Definitions: vascular endothelial growth factor receptor defined as following: A 180-kDa VEGF receptor found primarily in endothelial cells that is essential for vasculogenesis and vascular maintenance. It is also known as Flt-1 (fms-like tyrosine kinase receptor-1). A soluble, alternatively spliced isoform of the receptor may serve as a binding protein that regulates the availability of various ligands for VEGF receptor binding and signal transduction.. 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.. Midostaurin defined as following: A synthetic indolocarbazole multikinase inhibitor with potential antiangiogenic and antineoplastic activities. Midostaurin inhibits protein kinase C alpha (PKCalpha), vascular endothelial growth factor receptor 2 (VEGFR2), c-kit, platelet-derived growth factor receptor (PDGFR) and FMS-like tyrosine kinase 3 (FLT3) tyrosine kinases, which may result in disruption of the cell cycle, inhibition of proliferation, apoptosis, and inhibition of angiogenesis in susceptible tumors.. midostaurin defined as following: A synthetic indolocarbazole multikinase inhibitor with potential antiangiogenic and antineoplastic activities. Midostaurin inhibits protein kinase C alpha (PKCalpha), vascular endothelial growth factor receptor 2 (VEGFR2), c-kit, platelet-derived growth factor receptor (PDGFR) and FMS-like tyrosine kinase 3 (FLT3) tyrosine kinases, which may result in disruption of the cell cycle, inhibition of proliferation, apoptosis, and inhibition of angiogenesis in susceptible tumors..", "label": "yes"}
{"id": "converted_3402", "sentence1": "Does promoter shape vary across populations?", "sentence2": "Promoter shape varies across populations and affects promoter evolution and expression noise., Animal promoters initiate transcription either at precise positions (narrow promoters) or dispersed regions (broad promoters), a distinction referred to as promoter shape. Although highly conserved, the functional properties of promoters with different shapes and the genetic basis of their evolution remain unclear. Here we used natural genetic variation across a panel of 81 Drosophila lines to measure changes in transcriptional start site (TSS) usage, identifying thousands of genetic variants affecting transcript levels (strength) or the distribution of TSSs within a promoter (shape). Our results identify promoter shape as a molecular trait that can evolve independently of promoter strength. Broad promoters typically harbor shape-associated variants, with signatures of adaptive selection. Single-cell measurements demonstrate that variants modulating promoter shape often increase expression noise, whereas heteroallelic interactions with other promoter variants alleviate these effects. These results uncover new functional properties of natural promoters and suggest the minimization of expression noise as an important factor in promoter evolution., Promoter shape varies across populations and affects promoter evolution and expression noise[SEP]Relations: promoter clearance from RNA polymerase I promoter has relations: bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript, bioprocess_bioprocess with promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript. HIV Transcription Initiation has relations: pathway_protein with POLR2G, pathway_protein with POLR2G, pathway_protein with POLR2J, pathway_protein with POLR2J, pathway_protein with CCNH, pathway_protein with CCNH. Definitions: variants defined as following: An alteration or difference from a norm or standard.. promoter defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. TSS defined as following: A rare acute life-threatening systemic bacterial noncontagious illness caused by any of several related staphylococcal exotoxins. It is characterized by high fever, hypotension, rash, multi-organ dysfunction, and cutaneous desquamation during the early convalescent period. The toxins affect the host immune system, causing an exuberant and pathological host inflammatory response. Laboratory findings include leukocytosis, elevated prothrombin time, hypoalbuminemia, hypocalcemia, and pyuria.. transcriptional start site defined as following: The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.. transcript defined as following: The initial RNA molecule produced by transcription..", "label": "yes"}
{"id": "converted_1369", "sentence1": "Are microRNA (miR) regulated through DNA methylation of their promoters?", "sentence2": "We found that Tcf3 down-regulation in the context of constitutively active Wnt signaling does not result from promoter DNA methylation but is likely to be caused by a plethora of mechanisms at both the RNA and protein level as shown by the observed decrease in activating histone marks (H3K4me3 and H3-acetylation) and the upregulation of miR-211, a novel Wnt-regulated microRNA that targets Tcf3 and attenuates early neural differentiation in mouse ESCs, ene silencing of MIR22 in acute lymphoblastic leukaemia involves histone modifications independent of promoter DNA methylation, Whereas a CpG island was identified within the promoter element of MIR22, no promoter DNA methylation was detected in these cells, xtensive promoter DNA hypermethylation and hypomethylation is associated with aberrant microRNA expression in chronic lymphocytic leukemia, Integration of DNA methylation and miRNA promoter data led to the identification of 128 recurrent miRNA targets for aberrant promoter DNA methylation, Together, our findings characterize the role of epigenetic changes in the regulation of miRNA transcription and create a repository of disease-specific promoter regions that may provide additional insights into the pathogenesis of CLL, NA methylation of microRNA genes in multiple myeloma, Recently, epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation has been implicated in human cancers, including multiple myeloma (MM), ethylation of tumor suppressor microRNAs, Dysregulation of miRNA expression involved in cancer can be triggered by multiple mechanisms including aberrant DNA methylation of the miRNA gene promoter, Of note, DNA methylation of tumor suppressor miRNAs has been implicated in various human cancers, Moreover, miRNA silencing mediated by aberrant promoter DNA methylation can potentially be reversed by hypomethylating agents, and hence may pose a new therapeutic target in cancer, In this review, the authors will focus on the aberrant methylation of miRNAs in the pathogenesis of lymphoid malignancies including chronic lymphocytic leukemia, multiple myeloma and acute lymphoblastic leukemia, Here, we review those miRNAs implicated in AD that are regulated by promoter DNA methylation and/or chromatin modifications and, which frequently direct the expression of constituents of the epigenetic machinery, concluding with the delineation of a complex epigenetic-miRNA regulatory network and its alterations in AD, Furthermore, we also discuss epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation and the interaction of DNA methylation with miRNAs involved in the regulation of HSC activation and liver fibrosi, Instead, the cell type-specific silencing of these genes is due to enhanced p21 mRNA degradation, 14-3-3sigma promoter DNA methylation and reduced processing of the miR-34a primary transcript, Some tumor-suppressive miRNAs are known to be epigenetically silenced by promoter DNA methylation in cancer, In the present study, we aimed to identify miRNA genes that are silenced by DNA hypermethylation in hepatocellular carcinoma (HCC), It was found that miR-335, which is harbored within an intron of its protein-coding host gene, MEST, was downregulated by aberrant promoter hypermethylation via further methylation assays, including methylation-specific PCR, combined bisulfite and restriction analysis, bisulfite sequencing analysis and 5-aza-2'-deoxycytidine treatment, he levels of miR-335/MEST methylation were significantly higher in 18 (90%) out of 20 primary HCC tumors, compared to their non-tumor tissue counterparts (P<0.001), In conclusion, our results indicate that expression of miR-335 is reduced by aberrant DNA methylation in HCC.[SEP]Relations: promoter clearance from RNA polymerase I promoter has relations: bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript, bioprocess_bioprocess with promoter clearance from RNA polymerase I promoter for nuclear large rRNA transcript. histone modification has relations: bioprocess_bioprocess with histone methylation, bioprocess_bioprocess with histone methylation, bioprocess_bioprocess with histone biotinylation, bioprocess_bioprocess with histone biotinylation. MEST has relations: bioprocess_protein with regulation of lipid storage, bioprocess_protein with regulation of lipid storage. Definitions: histone modifications defined as following: The covalent alteration of one or more amino acid residues within a histone protein. [GOC:krc]. cancer defined as following: A malignant tumor at the original site of growth.. intron defined as following: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.. acute lymphoblastic leukemia defined as following: A type of ALL characterized by elevated levels of B-cell lymphoblasts in the bone marrow and the blood. [NCIT:C8644]. HSC defined as following: Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood.. CpG island defined as following: Areas of increased density of the dinucleotide sequence cytosine--phosphate diester--guanine. They form stretches of DNA several hundred to several thousand base pairs long. In humans there are about 45,000 CpG islands, mostly found at the 5' ends of genes. They are unmethylated except for those on the inactive X chromosome and some associated with imprinted genes.. CLL defined as following: A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.. MIR22 defined as following: This gene may be involved in the regulation of target gene transcription.. microRNA defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. Tcf3 defined as following: Human TCF7L1 wild-type allele is located in the vicinity of 2p11.2 and is approximately 177 kb in length. This allele, which encodes transcription factor 7-like 1 protein, is involved in Wnt pathway-dependent transcriptional regulation.. MM defined as following: A unit of concentration (molarity unit) equal to one thousandth of a mole (10E-3 mole) of solute per one liter of solution.. 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.. promoter defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. 5-aza-2'-deoxycytidine defined as following: An azacitidine derivative and antineoplastic antimetabolite. It inhibits DNA methyltransferase to re-activate silent genes, limiting METASTASIS and NEOPLASM DRUG RESISTANCE. Decitabine is used in the treatment of MYELODISPLASTIC SYNDROMES, and ACUTE MYELOID LEUKEMIA.. multiple myeloma defined as following: A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.. 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.. miR-211 defined as following: Human MIR211 wild-type allele is located in the vicinity of 15q13.3 and is approximately 110 bp in length. This allele, which encodes MIR211 pre-miRNA, plays a role in gene regulation.. 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.. H3K4me3 defined as following: A post-translationally modified form of histone H3 where the lysine residue at position 4 is trimethylated. This modification may be a marker for areas of active gene expression.. 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). human defined as following: Members of the species Homo sapiens.. p21 defined as following: A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.. cancers defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. NA defined as following: A wild-type zebrafish line, the stock of which was obtained from an area east of Calcutta in a district called Nadia.. promoters defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription..", "label": "yes"}
{"id": "converted_356", "sentence1": "Is the yeast Μac1 transcription factor induced upon copper deficiency?", "sentence2": "Low-affinity copper transporter CTR2 is regulated by copper-sensing transcription factor Mac1p in Saccharomyces cerevisiae., The copper-depletion induced CTR2 transcription can be abrogated by genetic deletion of copper-sensing transcription factor Mac1p, Taken together, our results suggest that Mac1p can activate the expression of vacuolar copper transporter Ctr2p in response to copper deficiency, resulting in yeast resistance to copper starvation., The ablation of either MAC1 or AFT1 also abrogated CTR2 expression induced by copper depletion, Our further study revealed that exogenous Aft1p upregulates CTR2 transcription only in the presence of Mac1p, whereas exogenous Mac1p upregulates CTR2 transcription only in the presence of Aft1p., We previously reported that CTR2 can be upregulated by copper deficiency via copper-sensing transcription factor Mac1p., In Saccharomyces cerevisiae, transcriptional responses to copper deficiency are mediated by the copper-responsive transcription factor Mac1, Although Mac1 activates the transcription of genes involved in high affinity copper uptake during periods of deficiency, little is known about the mechanisms by which Mac1 senses or responds to reduced copper availability. , The catalytic activity of Sod1 is essential for Mac1 activation and promotes a regulated increase in binding of Mac1 to copper response elements in the promoter regions of genomic Mac1 target genes., In Saccharomyces cerevisiae, copper ions regulate gene expression through the two transcriptional activators, Ace1 and Mac1., Ace1 mediates copper-induced gene expression in cells exposed to stressful levels of copper salts, whereas Mac1 activates a subset of genes under copper-deficient conditions., Taken together, our results suggest that Mac1p can activate the expression of vacuolar copper transporter Ctr2p in response to copper deficiency, resulting in yeast resistance to copper starvation., In Saccharomyces cerevisiae, transcriptional responses to copper deficiency are mediated by the copper-responsive transcription factor Mac1., We previously reported that CTR2 can be upregulated by copper deficiency via copper-sensing transcription factor Mac1p., The yeast Mac1 protein is a copper-sensing transcription factor that is essential for both the activation and inactivation of genes required for high affinity copper ion transport., The copper-depletion induced CTR2 transcription can be abrogated by genetic deletion of copper-sensing transcription factor Mac1p. , Copper-mediated repression of the activation domain in the yeast Mac1p transcription factor., We previously reported that CTR2 can be upregulated by copper deficiency via copper-sensing transcription factor Mac1p. , In this study, we found that copper depletion can upregulate yeast CTR2 gene transcription while copper overload downregulate it. The copper-depletion induced CTR2 transcription can be abrogated by genetic deletion of copper-sensing transcription factor Mac1p.[SEP]Relations: Copper has relations: drug_protein with MT1F, drug_protein with MT1F, drug_protein with NME1, drug_protein with NME1, drug_protein with MT1A, drug_protein with MT1A, drug_protein with MT1M, drug_protein with MT1M, drug_protein with MTF1, drug_protein with MTF1. Definitions: copper defined as following: A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.. Sod1 defined as following: Superoxide dismutase [Cu-Zn] (154 aa, ~16 kDa) is encoded by the human SOD1 gene. This protein is involved in the conversion of superoxides into oxygen and hydrogen peroxide.. Ace1 defined as following: Human ACE wild-type allele is located in the vicinity of 17q23.3 and is approximately 45 kb in length. This allele, which encodes angiotensin-converting enzyme protein, is involved in both hydrolysis and the regulation of vasoconstriction. Mutation of the gene is associated with renal tubular dysgenesis and susceptibility to ischemic stroke, microvascular complications of diabetes type 3 and diabetic end-stage renal disease.. promoter regions defined as following: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.. 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.. 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.. copper deficiency defined as following: abnormally diminished concentration of copper in the blood.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"}
{"id": "converted_3349", "sentence1": "The LINCS L1000 data set contains gene expression data for drug treated human cells, yes or no?", "sentence2": " Library of Integrated Network-based Cellular Signatures (LINCS) L1000 dataset that measured changes in GE before and after treatment of human cells with over 20 000 small-molecule compounds including most of the FDA-approved drugs., The Library of Integrated Network-based Cellular Signatures (LINCS) L1000 big data provide gene expression profiles induced by over 10 000 compounds, shRNAs, and kinase inhibitors using the L1000 platform., The Library of Integrated Cellular Signatures (LINCS) project provides comprehensive transcriptome profiling of human cell lines before and after chemical and genetic perturbations., Recently, resources such as the Library of Integrated Network-Based Cellular Signatures (LINCS) L1000 database provide gene expression profiles induced by various chemical and genetic perturbations, The library of integrated network-based cellular signatures (LINCS) L1000 data set currently comprises of over a million gene expression profiles of chemically perturbed human cell lines., The LINCS L1000 data repository contains almost two million gene expression profiles for thousands of small molecules and drugs., The GE data is from the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 dataset that measured changes in GE before and after treatment of human cells with over 20 000 small-molecule compounds including most of the FDA-approved drugs.[SEP]Relations: AV node cell to bundle of His cell signaling has relations: bioprocess_protein with CACNA1G, bioprocess_protein with CACNA1G, bioprocess_bioprocess with cell-cell signaling involved in cardiac conduction, bioprocess_bioprocess with cell-cell signaling involved in cardiac conduction, bioprocess_bioprocess with AV node cell to bundle of His cell communication, bioprocess_bioprocess with AV node cell to bundle of His cell communication. blood group, lewis system has relations: disease_disease with Mendelian disease, disease_disease with Mendelian disease. Definitions: chemical defined as following: A substance with a defined atomic or molecular structure that results from, or takes part in, reactions involving changes in its structure, composition, or properties.. 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..", "label": "yes"}
{"id": "converted_2785", "sentence1": "Are whole-genome duplications more divergent than small-scale duplications in yeast?", "sentence2": " Also, we observe that transporter and glycolytic genes have a higher probability to be retained in duplicate after WGD and subsequent gene loss, both in the model as in S. cerevisiae, which leads to an increase in glycolytic flux after WGD, We show that the retention of genes in duplicate in the model, corresponds nicely with those retained in duplicate after the ancestral WGD in S. cerevisiae, Thus, our model confirms the hypothesis that WGD has been important in the adaptation of yeast to the new, glucose-rich environment that arose after the appearance of angiosperms., Whole-genome duplicates tend to exhibit less profound phenotypic effects when deleted, are functionally less divergent, and are associated with a different set of functions than their small-scale duplicate counterparts., The results uncover the WGD as a major source for the evolution of a complex interconnected block of transcriptional pathways., These selected pairs, both WGD and SSD, tend to have decelerated functional evolution, have higher propensities of co-clustering into the same protein complexes, and share common interacting partners., Moreover, we find additional transcriptional profiles that are suggestive of neo- and subfunctionalization of duplicate gene copies. These patterns are strongly correlated with the functional dependencies and sequence divergence profiles of gene copies., Functional and transcriptional divergence between the copies after gene duplication has been considered the main driver of innovations ., Whole-genome duplicates tend to exhibit less profound phenotypic effects when deleted, are functionally less divergent, and are associated with a different set of functions than their small-scale duplicate counterparts., Empirical data shows that whole-genome duplications (WGDs) are more likely to be retained than small-scale duplications (SSDs), though their relative contribution to the functional fate of duplicates remains unexplored.[SEP]Relations: developmental delay with autism spectrum disorder and gait instability has relations: disease_phenotype_positive with Recurrent hand flapping, disease_phenotype_positive with Recurrent hand flapping, disease_phenotype_positive with Narrow palate, disease_phenotype_positive with Narrow palate, disease_phenotype_positive with Self-mutilation, disease_phenotype_positive with Self-mutilation, disease_phenotype_positive with Unsteady gait, disease_phenotype_positive with Unsteady gait, disease_disease with syndromic intellectual disability, disease_disease with syndromic intellectual disability. Definitions: yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. SSD defined as following: Persistent difficulty with speech sound production such that it interferes with verbal communication.. transporter defined as following: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.. angiosperms defined as following: vascular plant with flower as a reproductive structure with microsporophylls protecting seed, fruit for seed dispersal; sporophyte generation is dominant; pollination may be by animal carriers; may be terrestrial or aquatic.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"}
{"id": "converted_724", "sentence1": "Are there any clinical trials of the effect of evening primrose oil on postmenopausal symptoms ?", "sentence2": "To analyze whether the time (morning/evening) of administration of a compound containing 60 mg of dry soy seed extract (glycine max) with 40% of total isoflavones, primrose oil and α-tocopherol modifies the effect on the climacteric syndrome., The object of this study was to evaluate the effect of different doses of a compound containing isoflavones 60 mg, primrose oil 440 mg and vitamin E 10 mg. (IOVE) on menopausal complaints. This was an open, multicentre, randomised, group comparative, efficacy and safety trial., Emphasis was placed on randomized, double-blind, placebo-controlled clinical trials, as these provide the best efficacy and safety data, Nonprescription therapies reviewed include black cohosh, dong quai, evening primrose oil, physical activity, phytoestrogens, and red clover, The effect of oral evening primrose oil on menopausal hot flashes: a randomized clinical trial., The aim of this study was to compare the efficacy of evening primrose with placebo in improvement of menopausal hot flashes. , The application of oral evening primrose oil compared with placebo for controlling hot flashes may decrease more the intensity of attacks , Our search identified 58 randomised controlled trials of which 11 involved the use of clonidine, six for SSRIs, four for gabapentin, seven for black cohosh, seven for red clover, 18 for phytoestrogens, two for ginseng, one for evening primrose,, Single clinical trials have found no benefit for dong quai, evening primrose oil,, Single clinical trials have found that dong quai, evening primrose oil,, To evaluate the efficacy of gamolenic acid provided by evening primrose oil in treating hot flushes and sweating associated with the menopause. DESIGN: Randomised, double blind, placebo controlled study.[SEP]Relations: Evening primrose oil has relations: drug_drug with Primidone, drug_drug with Primidone, drug_drug with Estradiol, drug_drug with Estradiol, drug_drug with Acetaminophen, drug_drug with Acetaminophen, drug_drug with Prednisone, drug_drug with Prednisone, drug_drug with Antipyrine, drug_drug with Antipyrine. Definitions: SSRIs defined as following: Any agent that increases the extracellular level of the neurotransmitter serotonin (5-HT) by inhibiting its reuptake into the presynaptic cell. Increased level in the synaptic cleft prolongs the action of 5-HT on the postsynaptic receptor. This type of agent is typically used as an antidepressant and in the treatment of anxiety disorders and some personality disorders. They are also typically effective and used in treating some cases of insomnia.. gamolenic acid defined as following: An omega-6 fatty acid produced in the body as the delta 6-desaturase metabolite of linoleic acid. It is converted to dihomo-gamma-linolenic acid, a biosynthetic precursor of monoenoic prostaglandins such as PGE1. (From Merck Index, 11th ed). gabapentin defined as following: A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of PARTIAL SEIZURES; NEURALGIA; and RESTLESS LEGS SYNDROME.. isoflavones defined as following: 3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position.. climacteric syndrome defined as following: A grouping of variable physical, vasomotor and psychological symptoms in climacteric females. Physical symptoms include: cessation of menses, headaches, fatigue, weight gain and vaginal dryness. Vasomotor symptoms typically include: palpitations, hot flashes and night sweats. Psychological symptoms may include: decrease in libido, emotional lability, difficulty concentrating and insomnia.. 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.. dong quai defined as following: An herbal extract derived from the root of the plant Angelica sinensis with possible antiinflammatory, antispasmodic, vasodilatory, estrogenic, and antitumor activities. Angelica sinensis contains volatile oils, including safrole, isosafrole, and n-butylphthalide; coumarin derivatives, including psoralens, bergapten, osthol, imperatorin, and oxypeucedanin; and ferulic acid. The coumarin derivatives in this agent may vasodilate and relax smooth muscle and may exhibit additive anticoagulant effects. Ferulic acid, a phenolic phytochemical present in plant cell walls, may neutralize free radicals such as reactive oxygen species. In addition, Angelica sinensis extract has been shown to inhibit the growth and induce apoptosis of glioblastoma mutltiforme brain tumor cells through p53-dependent and p53-independent pathways..", "label": "yes"}
{"id": "converted_3610", "sentence1": "Is g-H2AX a marker for double strand breaks?", "sentence2": "The specific phosphorylation of histone H2AX on serine residue 139, described as γ-H2AX, is an excellent indicator or marker of DNA double-strand breaks (DSBs). , expression of the DNA double-strand break marker gamma-H2AX (γH2AX) , pH2AX, a marker of the DNA double-strand break (DSB)[SEP]Relations: Serine has relations: drug_protein with SPTLC2, drug_protein with SPTLC2, drug_protein with SPTLC1, drug_protein with SPTLC1, drug_protein with SLC16A10, drug_protein with SLC16A10, drug_protein with AGXT, drug_protein with AGXT, contraindication with phosphorus metabolism disease, contraindication with phosphorus metabolism disease. Definitions: serine defined as following: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids..", "label": "yes"}
{"id": "converted_334", "sentence1": "Is exome sequencing efficient for the detection of germline mutations?", "sentence2": "Whole exome sequencing is an efficient and sensitive method for detection of germline mutations in patients with phaeochromcytomas and paragangliomas, Whole exome sequencing is sensitive, rapid and efficient for detection of PCC/PGL germline mutations., These results from deep sequencing demonstrate a higher mutational detection rate than reported with conventional sequencing methodology., We performed exome sequencing of germline DNA from members of the affected family. Exome-wide analysis identified a novel loss-of-function mutation in the BAP1 gene, previously suggested as a tumor suppressor., whole-exome sequencing has been widely applied in the identification of germline mutations underlying Mendelian disorders, somatic mutations in various cancers and de novo mutations in neurodevelopmental disorders.[SEP]Relations: adaptation to pheromone regulating conjugation with mutual genetic exchange has relations: bioprocess_bioprocess with negative adaptation of signaling pathway, bioprocess_bioprocess with negative adaptation of signaling pathway, bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with response to pheromone regulating conjugation with mutual genetic exchange, bioprocess_bioprocess with regulation of conjugation, bioprocess_bioprocess with regulation of conjugation. Paraganglioma has relations: disease_phenotype_positive with von Hippel-Lindau disease, disease_phenotype_positive with von Hippel-Lindau disease, disease_phenotype_positive with hereditary pheochromocytoma-paraganglioma, disease_phenotype_positive with hereditary pheochromocytoma-paraganglioma. Definitions: neurodevelopmental disorders defined as following: A childhood disorder that has a neurological basis and manifests as a developmental disability.. 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.. BAP1 gene defined as following: This gene is involved in cellular growth regulation and is purported to have tumor suppression activity.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"}
{"id": "converted_1044", "sentence1": "Does Chromatin Immunoprecipitation (ChIP) show a bias for highly expressed loci?", "sentence2": "However, several issues in the processing and analysis of ChIP-chip data have not been resolved fully, including the effect of background (mock control) subtraction and normalization within and across arrays, Proper normalization is essential for ChIP-chip experiments. The proposed normalization technique can correct systematic errors and compensate for the lack of mock control data, thus reducing the experimental cost and producing more accurate results., Subtraction of the mock (non-specific antibody or no antibody) control data is generally needed to eliminate the bias, but appropriate normalization obviates the need for mock experiments and increases the correlation among replicates, The proposed method can handle several control samples allowing for correction of multiple sources of bias simultaneously, However, the data generated will always contain noise due to e.g. repetitive regions or non-specific antibody interactions, The generation of high copy numbers of DNA fragments as an artifact of the PCR step in ChIP-seq is an important source of bias of this methodology, Here we describe several technical aspects of the ChIP-Seq assay that diminish bias and background noise and allow the consistent generation of high-quality data, This theoretical paper systematically characterizes the biases and properties of ChIP-seq data by comparing 62 separate publicly available datasets, using rigorous statistical models and signal processing techniques, We detected a chromatin-state bias: open chromatin regions yielded higher coverage, which led to false positives if not corrected, This bias had a greater effect on detection specificity than any base-composition bias, This problem turns out to be surprisingly difficult, even in simple pairwise comparisons, because of the significant level of noise in ChIP-seq data, We show that the ChIPnorm method removes most of the noise and bias in the data and outperforms other normalization methods, We investigated the impact of library amplification bias on the identification of allele-specific (AS) molecular events from high-throughput sequencing data derived from chromatin immunoprecipitation assays (ChIP-seq), The 238 loci, termed \"hyper-ChIPable\", were in highly expressed regions with strong polymerase II and polymerase III enrichment signals, and the correlation between transcription level and ChIP enrichment was not limited to these 238 loci but extended genome-wide, The localization of unrelated proteins, including the entire silencing complex, to the most highly transcribed genes was highly suggestive of a technical issue with the immunoprecipitations[SEP]Relations: heterochromatin organization involved in chromatin silencing has relations: bioprocess_bioprocess with chromatin organization involved in negative regulation of transcription, bioprocess_bioprocess with chromatin organization involved in negative regulation of transcription, bioprocess_protein with SMCHD1, bioprocess_protein with SMCHD1, bioprocess_bioprocess with heterochromatin organization, bioprocess_bioprocess with heterochromatin organization, bioprocess_bioprocess with heterochromatin maintenance, bioprocess_bioprocess with heterochromatin maintenance. positive regulation of peptide secretion has relations: bioprocess_protein with ADORA1, bioprocess_protein with ADORA1. Definitions: proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. ChIP-seq defined as following: A molecular genetic technique that combines chromatin immunoprecipitation (ChIP) with massively parallel DNA sequencing to map the binding sites of DNA-associated proteins in a sample of cells. First, crosslinked protein-DNA complexes are isolated using ChIP. Next, the crosslinks are broken, the proteins are removed and the purified DNA is modified with adaptor oligonucleotides to facilitate massively parallel DNA sequencing. Following sequencing, the DNA sequences that are obtained can be mapped to their genomic locations.. repetitive regions defined as following: Nucleotide sequences present in multiple copies in the genome. There are several types of repeated sequences. Interspersed (or dispersed) DNA repeats (Interspersed Repetitive Sequences) are copies of transposable elements interspersed throughout the genome. Flanking (or terminal) repeats (Terminal Repeat Sequences) are sequences that are repeated on both ends of a sequence, for example, the long terminal repeats (LTRs) on retroviruses. Direct terminal repeats are in the same direction and inverted terminal repeats are opposite to each other in direction. Tandem repeats (Tandem Repeat Sequences) are repeated copies which lie adjacent to each other. These can also be direct or inverted. The ribosomal RNA and transfer RNA genes belong to the class of middle repetitive DNA..", "label": "yes"}
{"id": "converted_4277", "sentence1": "Αre plants from the genus Strychnos the original source of curare?", "sentence2": "Poisons are widespread in plants and animals and humankind has often tried to turn them to its own advantage. Owing to their poisonous properties, some species of Strychnos genus have been employed mainly in hunting and fishing, as an adjunct to weapons used not only in the search of food and clothes, but also for preventing depredation by wild animals. They have been employed for martial and criminal purposes and also as a means of determining guilt or innocence. By their nature, poisons such as strychnine and curare affect the functioning of the victim's body; , The ethnobotanical uses of South American species of Strychnos L. (Loganiaceae) are reviewed, with the exception of their major rôle in the preparation of curare, which will be dealt with in detail elsewhere., VELOPMENT: Curare is prepared by boiling the roots, bark and stalks of different plants belonging to the Loganiaceae (Strychnos) and Menispermaceae families (Chondrodendron, Curarea and Abuta). , The history to about 1850 of the muscle-relaxant poison curare is discussed, especially the developments leading to the botanical identification of the plants that yield the alkaloidal active principles: Loganiaceae (Strychnos species) and Menispermaceae (Abuta, Chondrodendron, and Curarea species)., or centuries. The study reviews the historical and ethnographic aspects of the use of curares and timbós in the Amazonian region.DEVELOPMENT: Curare is prepared by boiling the roots, bark and stalks of different plants belonging to the Loganiaceae (Strychnos) and Menispermaceae families (Chondrod[SEP]Relations: Plantar pits has relations: disease_phenotype_positive with Darier disease, disease_phenotype_positive with Darier disease, disease_phenotype_positive with monosomy 9q22.3, disease_phenotype_positive with monosomy 9q22.3, disease_phenotype_positive with PTEN hamartoma tumor syndrome, disease_phenotype_positive with PTEN hamartoma tumor syndrome, phenotype_phenotype with Abnormality of the plantar skin of foot, phenotype_phenotype with Abnormality of the plantar skin of foot, disease_phenotype_positive with nevoid basal cell carcinoma syndrome, disease_phenotype_positive with nevoid basal cell carcinoma syndrome. Definitions: roots defined as following: The usually underground portions of a plant that serve as support, store food, and through which water and mineral nutrients enter the plant. (From American Heritage Dictionary, 1982; Concise Dictionary of Biology, 1990). guilt defined as following: Subjective feeling of having committed an error, offense or sin; unpleasant feeling of self-criticism. These result from acts, impulses, or thoughts contrary to one's personal conscience.. curare defined as following: Plant extracts from several species, including genera STRYCHNOS and Chondodendron, which contain TETRAHYDROISOQUINOLINES that produce PARALYSIS of skeletal muscle. These extracts are toxic and must be used with the administration of artificial respiration.. Loganiaceae defined as following: A plant family of the order Gentianales, subclass Asteridae, class Magnoliopsida. They have leaflike appendages at the base of the leafstalks, have terminal flower clusters. Petals have four or five overlapping lobes and the fruit is a capsule containing winged or wingless seeds.. plants defined as following: Multicellular, eukaryotic life forms of kingdom Plantae. Plants acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations. It is a non-taxonomical term most often referring to LAND PLANTS. In broad sense it includes RHODOPHYTA and GLAUCOPHYTA along with VIRIDIPLANTAE..", "label": "yes"}
{"id": "converted_3129", "sentence1": "Has Hesperidin any role as a Neuroprotective Agent?", "sentence2": "Neuroprotective effect of hesperetin and nano-hesperetin on recognition memory impairment and the elevated oxygen stress in rat model of Alzheimer's disease, Hesperidin attenuates depression-related symptoms in mice with mild traumatic brain injury, Neuroprotective Effects of Hesperidin on Cerebral Vasospasm, The neuroprotective effect of hesperidin in NMDA-induced retinal injury acts by suppressing oxidative stress and excessive calpain activation., This study suggests a potential neuroprotective role of hesperidin against 3-NP-induced Huntington's disease-like manifestations., Hesperidin potentiates the neuroprotective effects of diazepam and gabapentin against pentylenetetrazole-induced convulsions in mice: Possible behavioral, biochemical and mitochondrial alterations., Hesperidin, a flavanoglycone abundantly present in citrus fruits, is reported to have antioxidant, anti-inflammatory, and neuroprotective properties., PURPOSE\nHesperidin, a glycoside flavonoid, is thought to act as an anti-cancer agent, since it has been found to exhibit both pro-apoptotic and anti-proliferative effects in several cancer cell types., Hesperidin is a flavonone glycoside, belonging to the flavonoid family, which is widely found in Citrus species and acts as a potent antioxidant and anticancer agent., BACKGROUND\nHesperidin, a flavanone present in citrus fruits, has been identified as a potent anticancer agent because of its proapoptotic and antiproliferative characteristics in some tumor cells., Oxidative stress and cancer; the role of hesperidin, a citrus natural bioflavonoid, as a cancer chemoprotective agent., Our data suggests that hesperidin exerts its neuroprotective effect against rotenone due to its antioxidant, maintenance of mitochondrial function, and antiapoptotic properties in a neuroblastoma cell line., Taken together, these results demonstrate potent antioxidant and neuroprotective effects of hesperetin, implying its potential role in protecting neurons against various types of insults associated with many neurodegenerative diseases., The neuroprotective effect of hesperidin in NMDA-induced retinal injury acts by suppressing oxidative stress and excessive calpain activation.We found that hesperidin, a plant-derived bioflavonoid, may be a candidate agent for neuroprotective treatment in the retina, after screening 41 materials for anti-oxidative properties in a primary retinal cell culture under oxidative stress. , Neuroprotective effects of hesperidin, a plant flavanone, on rotenone-induced oxidative stress and apoptosis in a cellular model for Parkinson's disease.Rotenone a widely used pesticide that inhibits mitochondrial complex I has been used to investigate the pathobiology of PD both in vitro and in vivo. , Cytoprotective effects of hesperetin and hesperidin against amyloid β-induced impairment of glucose transport through downregulation of neuronal autophagy., Hesperidin potentiates the neuroprotective effects of diazepam and gabapentin against pentylenetetrazole-induced convulsions in mice: Possible behavioral, biochemical and mitochondrial alterations.Hesp possesses potent anticonvulsant activity which might be mediated through modulation of gamma-amino butyric acid/benzodiazepine receptor action., Antioxidant and neuroprotective effects of hesperidin and its aglycone hesperetin.The present study evaluated antioxidant and neuroprotective activities of hesperidin, a flavanone mainly isolated from citrus fruits, and its aglycone hesperetin using cell-free bioassay system and primary cultured rat cortical cells. , Potential neuroprotective effects of hesperidin on 3-nitropropionic acid-induced neurotoxicity in rats., Hesperidin inhibits glutamate release and exerts neuroprotection against excitotoxicity induced by kainic acid in the hippocampus of rats., Emerging evidences indicate hesperidin, a citrus flavanone, attenuates neurodegenerative processes and related complications., Potential anti-inflammatory effects of hesperidin from the genus Citrus., Antioxidant and neuroprotective effects of hesperidin and its aglycone hesperetin., Hesperidin is a flavonoid present in high concentration in citrus species and has numerous biological properties, principally antioxidant and anti-inflammatory.[SEP]Relations: Hesperetin has relations: drug_drug with Meperidine, drug_drug with Meperidine, drug_drug with Famotidine, drug_drug with Famotidine, drug_drug with Nevirapine, drug_drug with Nevirapine, drug_drug with Antipyrine, drug_drug with Antipyrine, drug_drug with Acenocoumarol, drug_drug with Acenocoumarol. Definitions: diazepam defined as following: A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.. cancer defined as following: A malignant tumor at the original site of growth.. flavonoid defined as following: A group of phenyl benzopyrans named for having structures like FLAVONES.. Hesperidin defined as following: A flavanone glycoside found in CITRUS fruit peels.. kainic acid defined as following: (2S-(2 alpha,3 beta,4 beta))-2-Carboxy-4-(1-methylethenyl)-3-pyrrolidineacetic acid. Ascaricide obtained from the red alga Digenea simplex. It is a potent excitatory amino acid agonist at some types of excitatory amino acid receptors and has been used to discriminate among receptor types. Like many excitatory amino acid agonists it can cause neurotoxicity and has been used experimentally for that purpose.. gabapentin defined as following: A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of PARTIAL SEIZURES; NEURALGIA; and RESTLESS LEGS SYNDROME.. anti-inflammatory defined as following: Substances that reduce or suppress INFLAMMATION.. pesticide defined as following: Chemicals used to destroy pests of any sort. The concept includes fungicides (FUNGICIDES, INDUSTRIAL); INSECTICIDES; RODENTICIDES; etc.. rotenone defined as following: A botanical insecticide that is an inhibitor of mitochondrial electron transport.. neurons defined as following: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. traumatic brain injury defined as following: A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.. neurotoxicity defined as following: Neurologic disorders caused by exposure to toxic substances through ingestion, injection, cutaneous application, or other method. This includes conditions caused by biologic, chemical, and pharmaceutical agents.. cancer cell defined as following: Cells of, or derived from, a malignant tumor.. neuroblastoma defined as following: A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51). mitochondrial complex I defined as following: A complex of over 40 proteins found in the inner mitochondrial membrane. This protein complex catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q10) and plays a role in the initiation of the mitochondrial electron transport chain.. Parkinson's disease defined as following: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75). 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.. PD defined as following: A score of 4 or 5 on a 5-point PET scale with an increase in intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment.. tumor cells defined as following: Cells of, or derived from, a tumor.. glycoside defined as following: Cyclopentanophenanthrenes with a 5- or 6-membered lactone ring attached at the 17-position and SUGARS attached at the 3-position. Plants they come from have long been used in congestive heart failure. They increase the force of cardiac contraction without significantly affecting other parameters, but are very toxic at larger doses. Their mechanism of action usually involves inhibition of the NA(+)-K(+)-EXCHANGING ATPASE and they are often used in cell biological studies for that purpose..", "label": "yes"}
{"id": "converted_3445", "sentence1": "Does radiation for tinea capitis increases brain tumor risk?", "sentence2": "Emphasis is placed on meningiomas resulting from childhood treatment for primary brain tumor or tinea capitis, exposure to dental x-rays, and exposure to atomic explosions in Hiroshima and Nagasaki. , It is well known that radiation can induce meningiomas. These tumors usually arise in patients with a history of low-dose radiation to the scalp for treatment of tinea capitis or high-dose radiation for a previous brain tumor. , This paper describes six cases of radiation-associated intracranial meningiomas in patients previously treated with low-dose radiation to the scalp for tinea capitis., After a median follow-up of 40 years, an ERR/Gy of 4.63 and 1.98 (95% CI = 2.43-9.12 and 0.73-4.69) and an EAR/Gy per 10(4) PY of 0.48 and 0.31 (95% CI = 0.28-0.73 and 0.12-0.53) were observed for benign meningiomas and malignant brain tumors, respectively. , The estimated ERR/Gy for malignant brain tumors decreased with increasing age at irradiation from 3.56 to 0.47 (P = 0.037), while no trend with age was seen for benign meningiomas. The ERR for both types of tumor remains elevated at 30-plus years after exposure., Although meningiomas are known to be induced by low doses of cranial irradiation, such as those given to treat tinea capitis, little experience has been reported on the induction of meningiomas by high-dose cranial irradiation. , The exposed rats had a greater incidence of pituitary chromophobe adenomas, epithelial and mesothelial cell tumors than the unexposed controls but the excessive occurrence of malignant gliomas that was observed in the monkeys was absent in the rats. , We have analyzed 60 cases of intra-axial brain tumors associated with antecedent radiation therapy. These include four new cases. The patients had originally received radiation therapy for three reasons: (a) cranial irradiation for acute lymphoblastic leukemia (ALL), (b) definitive treatment of CNS neoplasia, and (c) treatment of benign disease (mostly cutaneous infections). , Long-term follow-up for brain tumor development after childhood exposure to ionizing radiation for tinea capitis., Benign and malignant thyroid neoplasms after childhood irradiation for tinea capitis., There is evidence to show that moderate doses of ionising radiations given in childhood for tinea capitis are associated with a late risk of developing a meningioma, This paper describes six cases of radiation-associated intracranial meningiomas in patients previously treated with low-dose radiation to the scalp for tinea capitis., These tumors usually arise in patients with a history of low-dose radiation to the scalp for treatment of tinea capitis or high-dose radiation for a previous brain tumor., There is evidence to show that moderate doses of ionising radiations given in childhood for tinea capitis are associated with a late risk of developing a meningioma., In addition to high dose radiation-induced meningiomas, intracranial meningiomas were observed in patients who underwent low-dose radiation for tinea capitis in childhood, applied en mass to immigrants coming to Israel from the North Africa and the Middle East during the 1950., A 39-year-old male developed primary brain lymphoma 33 years after receiving scalp irradiation for tinea capitis., Secondary glioblastoma multiforme (sGBM) can occur after a long latency period following radiation treatment of various diseases including brain tumors, leukemia, and more benign disorders like tinea capitis., The main data come from series of patients who underwent radiotherapy during childhood: a high incidence of tumors of the nervous system is found after irradiation of one to a few grays as treatment of a benign disease (especially tinea capitis), as well as after irradiation at higher doses of a few tens of grays for the treatment of cancer (in particular cerebral irradiation in acute lymphoblastic leukaemia).[SEP]Relations: skin meningioma has relations: disease_disease with malignant tumor of meninges, disease_disease with malignant tumor of meninges, disease_disease with malignant dermis tumor, disease_disease with malignant dermis tumor, disease_disease with skin cancer, disease_disease with skin cancer. Brain neoplasm has relations: drug_effect with Nitisinone, drug_effect with Nitisinone, drug_effect with Sibutramine, drug_effect with Sibutramine. Definitions: intracranial meningiomas defined as following: A meningioma that arises within the cranial cavity.. acute lymphoblastic leukemia defined as following: A type of ALL characterized by elevated levels of B-cell lymphoblasts in the bone marrow and the blood. [NCIT:C8644]. meningiomas defined as following: A relatively common neoplasm of the CENTRAL NERVOUS SYSTEM that arises from arachnoidal cells. The majority are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Meningiomas have a predilection to arise from the parasagittal region, cerebral convexity, sphenoidal ridge, olfactory groove, and SPINAL CANAL. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2056-7). brain tumor defined as following: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.. leukemia defined as following: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006). benign meningiomas defined as following: A grade I, slowly growing meningioma. Only a minority of tumors recur following complete resection.. ALL defined as following: Leukemia with an acute onset, characterized by the presence of lymphoblasts in the bone marrow and the peripheral blood. It includes the acute B lymphoblastic leukemia and acute T lymphoblastic leukemia.. 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.. rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. scalp defined as following: The outer covering of the calvaria. It is composed of several layers: SKIN; subcutaneous connective tissue; the occipitofrontal muscle which includes the tendinous galea aponeurotica; loose connective tissue; and the pericranium (the PERIOSTEUM of the SKULL).. tinea capitis defined as following: Ringworm of the scalp and associated hair mainly caused by species of MICROSPORUM; TRICHOPHYTON; and EPIDERMOPHYTON, which may occasionally involve the eyebrows and eyelashes.. pituitary chromophobe adenomas defined as following: A benign tumor of the anterior pituitary in which the cells do not stain with acidic or basic dyes.. low-dose defined as following: A reduced quantity of a therapeutic agent prescribed to be taken at one time or at stated intervals.. malignant brain tumors defined as following: A primary or metastatic malignant neoplasm affecting the brain.. epithelial defined as following: A term that refers to the cells that make up the epithelial tissues. They are found in the skin, and in the parenchyma, surface and lumen of internal organs.. cutaneous infections defined as following: Infections of the skin that happen multiple times. [HPO:curators]. cranial irradiation defined as following: The exposure of the head to roentgen rays or other forms of radioactivity for therapeutic or preventive purposes..", "label": "yes"}
{"id": "converted_3111", "sentence1": "Does Axitinib prolong survival of Pancreatic Cancer patients?", "sentence2": "CONCLUSIONS: Axitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions., RESULTS: Among Japanese patients, median overall survival was not estimable (95% confidence interval, 7.4 months-not estimable) with axitinib/gemcitabine (n = 58) and 9.9 months (95% confidence interval, 7.4-10.5) with placebo/gemcitabine (n = 56) (hazard ratio 1.093 [95% confidence interval, 0.525-2.274]). Median survival follow-up (range) was 5.1 months (0.02-12.3) with axitinib/gemcitabine vs. 5.4 months (1.8-10.5) with placebo/gemcitabine. Similarly, no difference was detected in overall survival between axitinib/gemcitabine and placebo/gemcitabine in patients from North America or the European Union. , At an interim analysis in January, 2009, the independent data monitoring committee concluded that the futility boundary had been crossed. Median overall survival was 8·5 months (95% CI 6·9-9·5) for gemcitabine plus axitinib (n=314, data missing for two patients) and 8·3 months (6·9-10·3) for gemcitabine plus placebo (n=316; hazard ratio 1·014, 95% CI 0·786-1·309; one-sided p=0·5436). , INTERPRETATION: The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer. , INTERPRETATION\nThe addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer., However, as with other tyrosine kinase inhibitors of the same class, axitinib does not prolong overall survival; therefore, selection of second-line tyrosine kinase inhibitor therapy, including axitinib, must be carefully considered to maximize outcomes for each patient., CONCLUSIONS\nAxitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions., Similarly, no difference was detected in overall survival between axitinib/gemcitabine and placebo/gemcitabine in patients from North America or the European Union., Axitinib/gemcitabine, while tolerated, did not provide survival benefit over gemcitabine alone in patients with advanced pancreatic cancer from Japan or other regions., The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer.[SEP]Relations: Axitinib has relations: drug_drug with Panobinostat, drug_drug with Panobinostat, drug_drug with Proguanil, drug_drug with Proguanil, drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Entrectinib, drug_drug with Entrectinib, drug_drug with Dolutegravir, drug_drug with Dolutegravir. Definitions: axitinib defined as following: An orally bioavailable tyrosine kinase inhibitor. Axitinib inhibits the proangiogenic cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor (PDGF), thereby exerting an anti-angiogenic effect.. tyrosine kinase defined as following: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.. gemcitabine defined as following: A broad-spectrum antimetabolite and deoxycytidine analogue with antineoplastic activity. Upon administration, gemcitabine is converted into the active metabolites difluorodeoxycytidine diphosphate (dFdCDP) and difluorodeoxycytidine triphosphate (dFdCTP) by deoxycytidine kinase. dFdCTP competes with deoxycytidine triphosphate (dCTP) and is incorporated into DNA. This locks DNA polymerase thereby resulting in \"masked termination\" during DNA replication. On the other hand, dFdCDP inhibits ribonucleotide reductase, thereby decreasing the deoxynucleotide pool available for DNA synthesis. The reduction in the intracellular concentration of dCTP potentiates the incorporation of dFdCTP into DNA.. pancreatic cancer defined as following: A primary or metastatic malignant tumor involving the pancreas. Representative examples include carcinoma and lymphoma.. Axitinib defined as following: An orally bioavailable tyrosine kinase inhibitor. Axitinib inhibits the proangiogenic cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor receptor (PDGF), thereby exerting an anti-angiogenic effect.. Pancreatic Cancer defined as following: A primary or metastatic malignant tumor involving the pancreas. Representative examples include carcinoma and lymphoma..", "label": "no"}
{"id": "converted_4037", "sentence1": "Is Tocilizumab (Actemra) used to block/antagonize the IL-6 receptor?", "sentence2": "Preliminary clinical results have indicated that antagonism of the IL-6 receptor (IL-6R), including with the FDA-approved humanized monoclonal antibody tocilizumab, can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile., Tocilizumab, an anti-IL-6 receptor antibody, and corticosteroids were initially used to treat the increase in acute inflammatory proteins and the anasarca, resulting in decreased cytokine levels. , Tocilizumab, a monoclonal antibody against the IL-6 receptor, was initiated at a dose of 8 mg/kg every 4 weeks., we randomly assigned patients with type 2 diabetes or obesity to intravenous tocilizumab (an IL-6 receptor antagonist) , Clinical studies are investigating whether tocilizumab (anti-IL-6 receptor) can help preserve beta cell function in patients recently diagnosed with T1D, Tocilizumab (RoActemra or Actemra) is a recombinant humanized monoclonal antibody that acts as an interleukin (IL)-6 receptor antagonist., To increase the number of cycles of antigen binding and lysosomal degradation, we engineered tocilizumab (Actemra), an antibody against the IL-6 receptor (IL-6R), to rapidly dissociate from IL-6R within the acidic environment of the endosome (pH 6.0) while maintaining its binding affinity to IL-6R in plasma (pH 7.4)., Tocilizumab (Actemra; Genentech, Inc) is the first biologic therapy targeting the cytokine interleukin 6 (IL-6)., over, our findings showed that combination of tocilizumab (Actemra; Roche), an anti-IL-6R monoclonal antibody, with carboplatin synergistically inhibited growth and proliferation of the EOC cells and the most direct axis for IL-6 gene expression was NF-κB pathway.CONC, Roche is co-developing tocilizumab (Actemra, RoActemra), a humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody, with Chugai Pharmaceutical., Tocilizumab (TCZ) is a compound that inhibits the IL-6 receptor., Tocilizumab (TCZ), is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody which has a main use in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis (sJIA) and polyarticular juvenile idiopathic arthritis (pJIA)., the US Food and Drug Administration accepted a complete-response submission for the use of Actemra (tocilizumab), the first humanized IL-6 receptor-inhibiting monoclonal antibody, for the treatment of RA. Although thi, increase the number of cycles of antigen binding and lysosomal degradation, we engineered tocilizumab (Actemra), an antibody against the IL-6 receptor (IL-6R), to rapidly dissociate from IL-6R within the acidic environment of the endosome (pH 6.0) while maintaining its binding affinity to IL-6R in plasma (pH 7.4). Studies usin, present study, we have shown that the humanized anti-IL-6 receptor tocilizumab (Actemra) is also a potent inhibitor of IL-8 in TNBC cells. Similar ef, Roche is co-developing tocilizumab (Actemra, RoActemra), a humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody, with Chugai Pharmaceutical. Tocili, tory gene activation is inhibited in vitro by tocilizumab, a humanized antibody to IL6 receptor (IL6R). Tocilizumab, These lines of evidence indicate that tocilizumab is able to bind to both sIL-6R and mIL-6R and to inhibit IL-6 binding to its receptors, leading to the blockade of the IL-6 signaling through both sIL-6R and mIL-6R, but not block the signaling of other IL-6 family cytokines., Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family., In addition, tocilizumab had the ability to bind to human IL-6R expressing COS-7 cells and to suppress the growth of the IL-6-dependent myeloma cell line, KPMM2., To characterize the biological activity of tocilizumab, a humanized anti-human interleukin-6 receptor (IL-6R) monoclonal antibody, we examined its binding activity to both soluble IL-6R (sIL-6R) and membrane bound IL-6R (mIL-6R) and its neutralizing activity to other IL-6 family cytokines., Tocilizumab inhibited the proliferation of BaF/IL-6R induced by IL-6, but did not inhibit the proliferation of BaF/IL-11R, BaF/OSMR, BaF/LIFR and BaF/CNTFR cells induced by their corresponding cytokines., Moreover, tocilizumab suppressed the IL-6/sIL-6R complex-induced proliferation of human gp130-transfected cell, BAF-h130., In addition, tocilizumab had the ability to dissociate IL-6 and sIL-6R from their preformed complex., ELISA assay demonstrated that tocilizumab bound to sIL-6R and inhibited IL-6 binding to sIL-6R in a dose-dependent manner., Tocilizumab recognizes both the membrane-bound and the soluble form IL-6R and specifically blocks IL-6 actions., Humanized antihuman IL-6 receptor antibody, tocilizumab., Tocilizumab is a humanized antihuman IL-6 receptor antibody designed using genetic engineering technology., Tocilizumab is expected to ameliorate the autoimmune inflammatory diseases with IL-6 overproduction and has been clinically developed as a therapeutic agent for RA, systemic-onset and articular types of JIA, Crohn's disease, etc., Tocilizumab/Actemra is an anti-IL-6R antibody, which can competitively block IL-6 binding to the IL-6R., Tocilizumab (TCZ; RoActemra® or Actemra®) is a recombinant humanized monoclonal antibody that acts as an interleukin 6 (IL-6) receptor antagonist., In 2009 the US Food and Drug Administration accepted a complete-response submission for the use of Actemra (tocilizumab), the first humanized IL-6 receptor-inhibiting monoclonal antibody, for the treatment of RA., Tocilizumab binds to the interleukin-6 receptor (IL-6R) and thereby blocks signaling of the pro-inflammatory cytokine IL-6., Tocilizumab (RoActemra(®); Actemra(®)) is a recombinant humanized monoclonal antibody that acts as an interleukin-6 receptor antagonist.[SEP]Relations: Tocilizumab has relations: drug_protein with IL6R, drug_protein with IL6R, drug_drug with Elagolix, drug_drug with Elagolix, drug_drug with Acteoside, drug_drug with Acteoside, drug_drug with Metronidazole, drug_drug with Metronidazole, drug_drug with Atezolizumab, drug_drug with Atezolizumab. Definitions: IL-6 defined as following: A recombinant therapeutic agent which is chemically identical to or similar to the endogenous cytokine interleukin-6 (IL-6) with antiapoptotic, proinflammatory, antiinflammatory, proproliferative and proangiogenic activities. IL-6 binds to its receptor (IL-6R), activating a receptor-CD130 receptor complex; the CD130 portion of the complex is a signal transduction protein that activates JAK kinases and Ras-mediated signaling pathways, which in turn activate downstream signaling pathways, resulting in the activation of various transcription factors (STAT, ELK-1, NF-IL-6, etc.) and gene transcription. The physiological effects of IL-6 are complex and varied and include hematopoietic, pyrogenic and thermogenic, proinflammatory, antiinflammatory, proproliferative (anti-apoptotic), and angiogenic effects.. cytokine defined as following: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.. carboplatin defined as following: An organoplatinum compound that possesses antineoplastic activity.. anasarca defined as following: A condition that is characterized by the presence of generalized edema. Causes include congestive heart failure, liver failure, renal failure, and severe malnutrition.. RA defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. 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.. 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]. IL-8 defined as following: Binding to an interleukin-8 receptor. [GOC:go_curators]. interleukin-6 receptor defined as following: Cell surface receptors that are specific for INTERLEUKIN-6. They are present on T-LYMPHOCYTES, mitogen-activated B-LYMPHOCYTES, and peripheral MONOCYTES. The receptors are heterodimers of the INTERLEUKIN-6 RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR GP130.. interleukin 6 defined as following: A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.. sIL-6R defined as following: Soluble interleukin-6 receptor subunit alpha is encoded by the human IL6R gene. This protein, which is produced by metalloproteinase-mediated cleavage of the membrane-bound form, is involved in the modulation of interleukin-6-mediated signaling by CD4-positive T-lymphocytes.. 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). IL6R defined as following: Interleukin-6 receptor subunit alpha (468 aa, ~52 kDa) is encoded by the human IL6R gene. This protein plays a role in regulation of the immune response, interleukin-6-mediated signaling, and hematopoiesis.. T1D defined as following: A chronic condition characterized by minimal or absent production of insulin by the pancreas.. endosome defined as following: Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.. IL-6R defined as following: Combining with interleukin-6 and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity. [GOC:jl, GOC:signaling]. human defined as following: Members of the species Homo sapiens.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary..", "label": "yes"}
{"id": "converted_502", "sentence1": "Is Mycobacterium avium less susceptible to antibiotics than Mycobacterium tuberculosis?", "sentence2": "The prevalence of MAC lung infection in two inner city hospitals was four times higher than that of TB., Most patients with combined infection were clinically consistent with MTB and responded to anti MTB treatment alone., The triplex PCR developed by us could be used to detect and differentiate M. tuberculosis, M. avium and other mycobacteria in a single reaction tube., Twelve (15%) of the 80 blood cultures were positive for mycobacteria, with Mycobacterium avium being identified in 7 (8.8%) samples and M. tuberculosis in 5 (6.2%). , The antimycobacterial activities of RS-112997, RS-124922 and RS-118641, three capuramycin analogues that inhibit phospho-N-acetylmuramyl-pentapeptide translocase, were tested against clinical isolates of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium intracellulare, The MIC50/90 (mg/L) results for RS-118641 were: M. tuberculosis, 1/2; multidrug-resistant (MDR) M. tuberculosis, 0.5/2; M. avium, 4/8; and M. intracellulare, 0.06/0.5, These results suggest that capuramycin analogues exhibit strong antimycobacterial potential and should be considered for further evaluation in the treatment of M. tuberculosis and M. avium-M. intracellulare complex infections in humans., Mycobacterium avium causes disseminated infection in patients with acquired immune deficiency syndrome., Overall incidences of Mycobacterium tuberculosis (TB) and Mycobacterium avium complex (MAC) were 0.8 and 1.4 cases/100 person-years of follow-up (PYF), decreasing from 1.8 (TB) and 3.5 cases/100 PYF (MAC) before September 1995 to 0.3 and 0.2 cases/100 PYF after March 1997., Because M tuberculosis disease is preventable and curable and yet communicable, physicians should maintain a high degree of suspicion for tuberculosis in HIV-infected adults. In comparison, the goal of treating M avium complex in patients with advanced HIV disease is to reduce constitutional symptoms and improve survival., MAC pulmonary disease should be considered in the differential diagnosis of SPNs, even when encountered in geographic regions with a high prevalence of pulmonary tuberculosis., From April 2001 to February 2002, 80 blood samples from patients who were suspected to have disseminated mycobacterial infection, presenting fever and (preferably) a CD4 T cell count<100.0 cell/mL were investigated, IL-10 underlies distinct susceptibility of BALB/c and C57BL/6 mice to Mycobacterium avium infection and influences efficacy of antibiotic therapy., Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity. , Effective therapeutic regimens exist that are limited by the emergence of drug resistance and the inability of antibiotics to kill dormant organisms. , Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity., a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC),, Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity., tuberculosis appear to have different genetic mechanisms for resisting the effects of these antibiotics, with pks12 playing a relatively more significant role in MAC.[SEP]Relations: tuberculosis has relations: disease_disease with mycobacterial infectious disease, disease_disease with mycobacterial infectious disease, disease_disease with tuberculosis, avian, disease_disease with tuberculosis, avian. mycobacterium avium complex disease has relations: disease_disease with mycobacterial infectious disease, disease_disease with mycobacterial infectious disease, disease_disease with primary bacterial infectious disease, disease_disease with primary bacterial infectious disease. Recurrent mycobacterium avium complex infections has relations: disease_phenotype_positive with monocytopenia with susceptibility to infections, disease_phenotype_positive with monocytopenia with susceptibility to infections. Definitions: Mycobacterium avium complex defined as following: A nontuberculous infection when occurring in humans. It is characterized by pulmonary disease, lymphadenitis in children, and systemic disease in AIDS patients. Mycobacterium avium-intracellulare infection of birds and swine results in tuberculosis.. 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.. humans defined as following: Members of the species Homo sapiens.. Mycobacterium intracellulare defined as following: species found in lung lesions and secretions of humans; may cause bone and tendon-sheath lesions in rabbits; some strains are pathogenic for mice; linked to opportunistic infections in humans; not easily distinguished from Mycobacterium avium and therefore is included in the Mycobacterium avium Complex.. rifabutin 1 defined as following: A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients.. mycobacterial infection defined as following: Infections with bacteria of the genus MYCOBACTERIUM.. MTB defined as following: A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation.. pulmonary tuberculosis defined as following: MYCOBACTERIUM infections of the lung.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. IL-10 defined as following: Binding to interleukin-10. [GOC:jl]. Mycobacterium avium defined as following: A bacterium causing tuberculosis in domestic fowl and other birds. In pigs, it may cause localized and sometimes disseminated disease. The organism occurs occasionally in sheep and cattle. It should be distinguished from the M. avium complex, which infects primarily humans.. HIV disease defined as following: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).. TB defined as following: Any of the infectious diseases of man and other animals caused by species of MYCOBACTERIUM TUBERCULOSIS.. antibiotic defined as following: Substances naturally produced by microorganisms or their derivatives that selectively target microorganisms not humans. Antibiotics kill or inhibit the growth of microorganisms by targeting components of the microbial cell absent from human cells, including bacterial cell walls, cell membrane, and 30S or 50S ribosomal subunits. These substances are used in the treatment of bacterial and other microbial infections.. mycobacteria defined as following: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts..", "label": "yes"}
{"id": "converted_2512", "sentence1": "Is celiac disease caused by gliadin-induced transglutaminase-2 (TG2)-dependent events ?", "sentence2": "Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. , Celiac disease (CD) is an autoimmune enteropathy initiated and sustained by the ingestion of gluten in genetically susceptible individuals. It is caused by a dysregulated immune response toward both dietary antigens, the gluten proteins of wheat, rye, and barley, and autoantigens, the enzyme tissue transglutaminase (TG2), Celiac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of anti-transglutaminase 2 (TG2) and anti-gliadin antibodies, Transglutaminase 2 (TG2) catalyzes cross-linking or deamidation of glutamine residues in peptides and proteins. The in vivo deamidation of gliadin peptides plays an important role in the immunopathogenesis of celiac disease (CD)., Tissue transglutaminase (TG2) modifies proteins and peptides by transamidation or deamidation of specific glutamine residues. TG2 also has a central role in the pathogenesis of celiac disease. The enzyme is both the target of disease-specific autoantibodies and generates deamidated gliadin peptides recognized by intestinal T cells from patients.[SEP]Relations: celiac disease has relations: disease_protein with TGM2, disease_protein with TGM2, disease_protein with SOAT2, disease_protein with SOAT2, disease_protein with UGT1A4, disease_protein with UGT1A4, disease_protein with MAGI2, disease_protein with MAGI2, disease_protein with TFF1, disease_protein with TFF1. Definitions: proteins defined as following: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.. TG2 defined as following: Protein-glutamine gamma-glutamyltransferase 2 (687 aa, ~77 kDa) is encoded by the human TGM2 gene. This protein plays a role in both the induction of apoptosis and the formation of covalent bonds between peptide-bound glutamine and various primary amines.. peptides defined as following: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.. Transglutaminase 2 defined as following: Calcium-dependent acyltransferase that catalyzes cross-linking of proteins at a GLUTAMINE in one chain with primary amine such as in LYSINE in another chain. In addition it can also accept monoamine substrates to catalyze post-translational modifications (e.g., protein serotonylation).. autoantigens defined as following: Endogenous tissue constituents with the ability to interact with AUTOANTIBODIES and cause an immune response.. rye defined as following: A hardy EDIBLE GRAIN crop, rye, grown in northern climates. It is the most frequent host to ergot (CLAVICEPS), the toxic fungus. Its hybrid with TRITICUM is TRITICALE, another CEREAL crop.. Celiac disease defined as following: A malabsorption syndrome that is precipitated by the ingestion of foods containing GLUTEN, such as wheat, rye, and barley. It is characterized by INFLAMMATION of the SMALL INTESTINE, loss of MICROVILLI structure, failed INTESTINAL ABSORPTION, and MALNUTRITION.. gluten proteins defined as following: Prolamins in the endosperm of SEEDS from the Triticeae tribe which includes species of WHEAT; BARLEY; and RYE.. autoimmune enteropathy defined as following: A rare autoimmune disorder that usually affects children. It is associated with the presence of circulating autoantibodies that act against the gut epithelial cells. It is characterized by diarrhea and weight loss due to malabsorption.. celiac disease defined as following: A malabsorption syndrome that is precipitated by the ingestion of foods containing GLUTEN, such as wheat, rye, and barley. It is characterized by INFLAMMATION of the SMALL INTESTINE, loss of MICROVILLI structure, failed INTESTINAL ABSORPTION, and MALNUTRITION.. transglutaminase-2 defined as following: Protein-glutamine gamma-glutamyltransferase 2 (687 aa, ~77 kDa) is encoded by the human TGM2 gene. This protein plays a role in both the induction of apoptosis and the formation of covalent bonds between peptide-bound glutamine and various primary amines..", "label": "yes"}
{"id": "converted_3255", "sentence1": "Can Daptacel be used instead of IPOL?", "sentence2": "Our goal was to compare the safety and immunogenicity of a combination vaccine (DTaP(5)-IPV-Hib; Pentacel) with that of its separately administered, US-licensed equivalent vaccines (diphtheria, tetanus, 5-component acellular pertussis vaccine [DTaP(5); Daptacel], inactivated poliovirus vaccine [IPV; IPOL], and Haemophilus influenzae type b [Hib] vaccine [ActHIB]), when administered to infants and toddlers concomitantly with other routinely recommended vaccines and to assess antibody persistence from the fourth dose in toddlers to the fifth (preschool) DTaP(5) dose., DTaP(5)-IPV-Hib is a suitable replacement for separately administered DTaP, IPV, and Hib vaccines., In this randomized, multicenter study, 1939 healthy infants were immunized at 2, 4, and 6 months of age with 1 of 3 lots of DTaP(5) coadministered with IPV and Hib vaccines or 1 lot of DTaP(5)-IPV-Hib combination vaccine., DTaP(5)-IPV-Hib elicited similar or fewer solicited injection-site and systemic reactions as compared with the separate administration of US-licensed DTaP(5), IPV, and Hib vaccines. [SEP]Relations: Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated) has relations: drug_drug with Certolizumab pegol, drug_drug with Certolizumab pegol, drug_drug with Dactinomycin, drug_drug with Dactinomycin, drug_drug with Dacarbazine, drug_drug with Dacarbazine, drug_drug with Clobetasol, drug_drug with Clobetasol. Clostridium tetani toxoid antigen (formaldehyde inactivated) has relations: drug_drug with Dactinomycin, drug_drug with Dactinomycin. Definitions: 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]. DTaP(5)-IPV-Hib defined as following: A vaccine consisting of detoxified diphtheria toxoid (D), detoxified tetanus toxoid (T), acellular pertussis (aP) antigens, inactivated poliovirus (IPV) types 1, 2 and 3, and Haemophilus influenzae type b (Hib) capsular polysaccharide (polyribosylribitol phosphate; PRP) covalently bound to tetanus protein, suspended in water for injection and with active immunizing activity against diphtheria, tetanus, pertussis, poliomyelitis and H. influenzae type b. The five purified pertussis antigens in this vaccine are pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN) and fimbriae types 2 and 3 (FIM). Upon intramuscular injection of the diphtheria-tetanus-acellular pertussis-inactivated poliomyelitis-Haemophilus influenzae type b vaccine (DTaP-IPV-Hib), this vaccine activates the immune system to develop antibodies against diphtheria toxin, tetanus toxin, B. pertussis antigens, polioviruses and Hib, thereby providing active immunization against these diseases. The diphtheria and tetanus toxoids and pertussis antigens (inactivated PT, FHA, PRN and FIM) are adsorbed separately onto aluminum phosphate and then combined with IPV and PRP.. diphtheria defined as following: A localized infection of mucous membranes or skin caused by toxigenic strains of CORYNEBACTERIUM DIPHTHERIAE. It is characterized by the presence of a pseudomembrane at the site of infection. DIPHTHERIA TOXIN, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects.. vaccines defined as following: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases.. tetanus defined as following: A preparation of formaldehyde-deactivated toxin isolated from the bacterium Clostridium tetani. Tetanus toxoid is used for booster injection and can stimulate the production of antitoxin antibodies. This agent may be used as an adjuvant in cancer vaccines..", "label": "no"}
{"id": "converted_4203", "sentence1": "Does AZD3759 cross the blood brain barrier?", "sentence2": "AZD3759, an EGFR tyrosine kinase inhibitors (TKIs) with excellent blood-brain barrier (BBB) penetration,, AZD3759, a BBB-penetrating EGFR inhibitor for the treatment of EGFR mutant NSCLC with CNS metastases, We report the discovery and early clinical development of AZD3759, a selective EGFR inhibitor that can fully penetrate the blood-brain barrier (BBB),, AZD3759 is a novel EGFR tyrosine kinase inhibitor with high capability to penetrate the blood-brain barrier. , We report the discovery and early clinical development of AZD3759, a selective EGFR inhibitor that can fully penetrate the blood-brain barrier (BBB), with equal free concentrations in the blood, cerebrospinal fluid, and brain tissue., Another promising class of EGFR TKI such as AZD3759 has been designed to penetrate blood brain barrier to treat brain metastases and leptomeningeal disease and has showed promising responses in patients with brain metastases., AZD3759 is a novel EGFR tyrosine kinase inhibitor with high capability to penetrate the blood-brain barrier., In our study, we demonstrated that AZD3759, an EGFR tyrosine kinase inhibitors (TKIs) with excellent blood-brain barrier (BBB) penetration, combined with radiation enhanced the antitumor efficacy in BM model from EGFR mutant (EGFRm) NSCLC., sing class of EGFR TKI such as AZD3759 has been designed to penetrate blood brain barrier to treat brain metastases and leptomeningeal disease and has showed promising responses in patients with brain metastases. Acquired re, discovery and early clinical development of AZD3759, a selective EGFR inhibitor that can fully penetrate the blood-brain barrier (BBB), with equal free concentrations in the blood, cerebrospinal fluid, and brain tissue. Treatment with A, AZD3759, a BBB-penetrating EGFR inhibitor for the treatment of EGFR mutant NSCLC with CNS metastases., our study, we demonstrated that AZD3759, an EGFR tyrosine kinase inhibitors (TKIs) with excellent blood-brain barrier (BBB) penetration, combined with radiation enhanced the antitumor efficacy in BM model from EGFR mutant (EGFRm) NSCLC. Besides, t, in patients with BM and LM treated with AZD3759 confirms its BBB-penetrant properties and antitumor activities. Our data demonstrate , ood penetration of the blood-brain barrier by AZD3759, and its promising clinical activity, support further assessment of this compound in studies.FUNDI, The next generation EGFR TKIs osimertinib and AZD3759 have improved BBB penetration and the BLOOM study of osimertinib and AZD3759 has reported highly promising intracranial efficacy and may herald a new frontier to treat this therapeutically challenging subset of advanced EGFR mutant patients., The results showed the BBB penetration of AZD3759 was decreased within 24 hr after radiation, however, the free concentration of AZD3759 in brain kept at a high level in the context of radiation., We also detected the BBB penetration of AZD3759 when combined with cranial radiation., good penetration of the blood-brain barrier by AZD3759, and its promising clinical activity, support further assessment of this compound in studies.FUND, n pretreated with a tyrosine kinase inhibitor. The good penetration of the blood-brain barrier by AZD3759, and its promising clinical activity, support further asse, An early clinical study in patients with BM and LM treated with AZD3759 confirms its BBB-penetrant properties and antitumor activities.[SEP]Relations: blood brain barrier has relations: anatomy_anatomy with glial blood brain barrier, anatomy_anatomy with glial blood brain barrier, anatomy_anatomy with cell layer, anatomy_anatomy with cell layer. central nervous system has relations: anatomy_protein_present with AZIN1, anatomy_protein_present with AZIN1, anatomy_protein_present with ZNF609, anatomy_protein_present with ZNF609, anatomy_protein_present with TBC1D9, anatomy_protein_present with TBC1D9. Definitions: AZD3759 defined as following: An orally available inhibitor of the epidermal growth factor receptor (EGFR), with potential antineoplastic activity. Upon oral administration, AZD3759 binds to and inhibits the activity of EGFR as well as certain mutant forms of EGFR. This prevents EGFR-mediated signaling, and may lead to both induction of cell death and inhibition of tumor growth in EGFR-overexpressing cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. Check for \"https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/C118289\" active clinical trials using this agent. (\"http://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI%20Thesaurus&code=C118289\" NCI Thesaurus). BM defined as following: The normal process of elimination of fecal material from the RECTUM.. EGFR tyrosine kinase inhibitors defined as following: Any tyrosine kinase inhibitor that targets the activity of the epidermal growth factor receptor (EGFR) tyrosine kinase. Inhibition of epidermal growth factor receptor tyrosine kinase may inhibit the growth of epidermal-lineage tumor cells, especially those that overexpress epidermal growth factor receptor.. mutant defined as following: An altered form of an individual, organism, population, or genetic character that differs from the corresponding wild type due to one or more alterations (mutations).. NSCLC defined as following: A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.. cerebrospinal fluid defined as following: A watery fluid that is continuously produced in the CHOROID PLEXUS and circulates around the surface of the BRAIN; SPINAL CORD; and in the CEREBRAL VENTRICLES.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. tyrosine kinase inhibitor defined as following: Protein kinase inhibitors that inhibit TYROSINE PROTEIN KINASES..", "label": "yes"}
{"id": "converted_827", "sentence1": "Are histone deacetylase (HDAC) inhibitors good candidates to control metastasis of solid tumors?", "sentence2": "JNJ-26481585 also fully inhibited the growth of C170HM2 colorectal liver metastases, whereas again 5-fluorouracil/Leucovorin showed modest activity., Although not meeting the RECIST response criteria for adequate single-agent activity, the observed tolerable toxicities and the potential for clinical benefit in terms of stable disease suggest that further assessment of vorinostat as a part of combination therapy with either chemotherapeutic or targeted agents in metastatic breast might be undertaken., Treatments of different structural classes of HDACi simultaneously induced cell death and promoted cell migration and metastasis in multiple cancer cell types. Suppression of HDACi-induced PKCs leads to development of low toxic and long-term therapeutic strategies to potentially treat cancer as a chronic disease., mRNA expression analysis of lung tumor bearing mice suggested that the enhanced chemopreventive activity of the combination is related to atorvastatin modulation of DNA repair, SAHA modulation of angiogenesis, and both drugs modulating invasion and metastasis pathways., Histone deacetylase (HDAC) inhibitors induced morphologic differentiation, cell-cycle exit, and a shift to a differentiated, melanocytic gene expression profile in cultured UM cells. VPA inhibited the growth of UM tumors in vivo., When both drugs were used in concert additive effects were observed on the migratory and invasive behavior but not on tumor-endothelium and tumor-matrix interaction. Separate mTOR or HDAC inhibition slows processes related to tumor metastasis. The RAD001-VPA combination showed advantage over VPA monotreatment with particular respect to migration and invasion., In conclusion, sequential treatments of mice with MS-275 followed by TRAIL may target multiple pathways to reverse EMT and inhibit tumor progression, angiogenesis, and metastasis and represent a novel therapeutic approach to treat cancer., In vivo, AA98 synergized with vorinostat to inhibit tumor growth and metastasis., We report the first preclinical data for the prevention of brain metastasis of triple-negative breast cancer. Vorinostat is brain permeable and can prevent the formation of brain metastases by 62%. Its mechanism of action involves the induction of DNA double-strand breaks, suggesting rational combinations with DNA active drugs or radiation., Combining vorinostat with radiation may be a potential treatment option for patients with breast cancer who develop brain metastases., Although single-agent PCI-24781 had modest effects on STS growth and metastasis, marked inhibition was observed when combined with chemotherapy., In a 4T1 metastatic breast carcinoma model, AN-7 inhibited the formation of lung lesions by 76% and AN-9 by 47%, further demonstrating the greater efficacy of AN-7 compared to AN-9 (P<0.02). Both AN-7 and AN-9 exhibited antimetastatic and antiangiogenic activities by reducing vascularization, bFGF expression and HIF-1alpha., Since prolonged oral administration with 50 mg/kg or a single oral dose of 1.2 g/kg AN-7 did not cause adverse effects and the former exhibited significant anticancer activity, AN-7 is likely to display a high therapeutic index and may be beneficial for prostate cancer patients., We show that apicidin significantly inhibits H-ras-induced invasive phenotype of MCF10A human breast epithelial cells in parallel with a specific downregulation of matrix metalloproteinase (MMP)-2, but not MMP-9. We also show that apicidin induces a morphological reversal and growth inhibition of H-ras MCF10A cells similar to that induced by other HDAC inhibitors., We also found that NaB induced three genes, which are known metastatic suppressors, and downregulated 11 genes, which have been shown to promote metastasis.[SEP]Relations: Valproic acid has relations: drug_protein with HDAC9, drug_protein with HDAC9, drug_protein with HDAC2, drug_protein with HDAC2. Vorinostat has relations: drug_protein with HDAC3, drug_protein with HDAC3, drug_protein with HDAC1, drug_protein with HDAC1, drug_protein with HDAC6, drug_protein with HDAC6. Definitions: cancer defined as following: A malignant tumor at the original site of growth.. prostate cancer defined as following: A primary or metastatic malignant tumor involving the prostate gland. The vast majority are carcinomas.. vorinostat defined as following: A synthetic hydroxamic acid derivative with antineoplastic activity. Vorinostat, a second generation polar-planar compound, binds to the catalytic domain of the histone deacetylases (HDACs). This allows the hydroxamic moiety to chelate zinc ion located in the catalytic pockets of HDAC, thereby inhibiting deacetylation and leading to an accumulation of both hyperacetylated histones and transcription factors. Hyperacetylation of histone proteins results in the upregulation of the cyclin-dependant kinase p21, followed by G1 arrest. Hyperacetylation of non-histone proteins such as tumor suppressor p53, alpha tubulin, and heat-shock protein 90 produces additional anti-proliferative effects. This agent also induces apoptosis and sensitizes tumor cells to cell death processes. Vorinostat crosses the blood-brain barrier.. lung tumor defined as following: Tumors or cancer of the LUNG.. MMP-9 defined as following: An endopeptidase that is structurally similar to MATRIX METALLOPROTEINASE 2. It degrades GELATIN types I and V; COLLAGEN TYPE IV; and COLLAGEN TYPE V.. toxicities defined as following: The finding of bodily harm due to the poisonous effects of something.. triple-negative breast cancer defined as following: An invasive breast carcinoma which is negative for expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).. VPA defined as following: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.. HIF-1alpha defined as following: Hypoxia-inducible factor 1-alpha (826 aa, ~93 kDa) is encoded by the human HIF1A gene. This protein plays a role in transcriptional regulation in response to hypoxia.. mTOR defined as following: Serine/threonine-protein kinase mTOR (2549 aa, ~289 kDa) is encoded by the human MTOR gene. This protein is involved in protein phosphorylation, signaling and cell growth.. TRAIL defined as following: Human TNFSF10 wild-type allele is located within 3q26 and is approximately 18 kb in length. This allele, which encodes tumor necrosis factor ligand superfamily member 10 protein, is involved in the induction and modulation of apoptosis.. STS defined as following: An anionic surface-active agent used for its wetting properties in industry and used in medicine as an irritant and sclerosing agent for hemorrhoids and varicose veins.. RECIST defined as following: Standard parameters to be used when documenting response of solid tumors to treatment; a set of published rules that define when cancer patients improve (\"respond\"), stay the same (\"stable\"), or worsen (\"progression\") during treatments. (from www.recist.com). H-ras defined as following: Human HRAS wild-type allele is located in the vicinity of 11p15.5 and is approximately 3 kb in length. This allele, which encodes GTPase HRas protein, is involved in cellular mitogenesis. Mutations of HRAS are implicated in Costello syndrome, bladder cancer and oral squamous cell carcinoma.. 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).. 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.. atorvastatin defined as following: A synthetic lipid-lowering agent. Atorvastatin competitively inhibits hepatic hydroxymethyl-glutaryl coenzyme A (HMG-CoA) reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate, a key step in cholesterol synthesis. Atorvastatin also increases the number of LDL receptors on hepatic cell surfaces to enhance uptake and catabolism of LDL and reduces LDL production and the number of LDL particles. This agent lowers plasma cholesterol and lipoprotein levels and modulates immune responses by suppressing MHC II (major histocompatibility complex II) on interferon gamma-stimulated, antigen-presenting cells such as human vascular endothelial cells. (NCI04). genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. HDAC defined as following: Human HDAC9 wild-type allele is located in the vicinity of 7p21.1 and is approximately 910 kb in length. This allele, which encodes histone deacetylase 9 protein, is involved in the modification of histones.. solid tumors defined as following: A benign or malignant neoplasm arising from tissues that do not include fluid areas. Representative examples include epithelial neoplasms (e.g. lung carcinoma, prostate carcinoma, breast carcinoma, colon carcinoma), and neoplasms arising from the soft tissues and bones (e.g. leiomyosarcoma, liposarcoma, chondrosarcoma, osteosarcoma). Neoplasms originating from the blood or bone marrow (leukemias and myeloproliferative disorders) are not considered solid tumors..", "label": "yes"}
{"id": "converted_3545", "sentence1": "Does the BRAFV600E mutation have an effect on clinical response to radioiodine therapy?", "sentence2": "Preclinical studies showed that BRAF mutation significantly reduced radioiodine uptake and decreased the sensitivity to radioactive iodine (RAI) therapy., The status of BRAF mutation may not affect the clinical response to RAI therapy for patients with PTMC with intermediate-risk to high-risk features. More trials examining the role of BRAF mutation in guiding postoperative RAI therapy are needed., our results suggest that the combination of BRAFV600E+ve mutation and MIBI-ve scintigraphy may be considered a negative prognostic clue, which predicts the absence of radioiodine uptake at pT-WBS in DTC patients with incomplete bio-chemical response to first RAIT, The results indicate that BRAF(V600E) mutation is correlated with a lower expression of NIS in PTCs without HT, suggesting the radioiodine-refractory effects during RIA therapy in these patients.[SEP]Relations: SLC5A5 has relations: drug_protein with Iodine, drug_protein with Iodine, disease_protein with hereditary site-specific ovarian cancer syndrome, disease_protein with hereditary site-specific ovarian cancer syndrome, bioprocess_protein with cellular response to cAMP, bioprocess_protein with cellular response to cAMP, disease_protein with hereditary breast ovarian cancer syndrome, disease_protein with hereditary breast ovarian cancer syndrome, disease_protein with familial ovarian cancer, disease_protein with familial ovarian cancer. Definitions: NIS defined as following: This gene is involved in iodide transport.. RAI defined as following: Human PPP1R13L wild-type allele is located in the vicinity of 19q13.32 and is approximately 27 kb in length. This allele, which encodes RelA-associated inhibitor protein, plays a role in the modulation of both apoptosis and transcription.. HT defined as following: An autoimmune disorder caused by the production of autoantibodies against thyroid tissue. There is progressive destruction of the thyroid follicles leading to hypothyroidism.. BRAF defined as following: Serine/threonine-protein kinase B-raf (766 aa, ~84 kDa) is encoded by the human BRAF gene. This protein plays a role in protein phosphorylation, mitogenesis and neuronal signal transduction.. mutation defined as following: Any transmissible change in the genetic material of an organism, which can result from radiation, viral infection, transposition, treatment with mutagenic chemicals and errors during DNA replication or meiosis. The effects of mutation range from single base changes to loss or gain of complete chromosomes. As many of the simpler alterations to DNA may be repaired, such changes are only heritable once the change is fixed in the DNA by the process of replication. Mutations may be associated with genetic diversity or with pathologies including cancer..", "label": "yes"}
{"id": "converted_1082", "sentence1": "Are there any Decision support systems for chronic pain management ?", "sentence2": "a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS), We based the DSS on the existing ATHENA-DSS, Use of this iterative process led to development of a multifunctional DSS, interactive decision dashboard format, We created a computerized, interactive clinical decision dashboard , Interactive decision dashboards can be adapted for clinical use and have the potential to foster informed decision making., Clinical decision support systems are promising tools for improving behavioral medicine care for chronic pain., Improving Patient Safety Using ATHENA-Decision Support System Technology: , ATHENA-DSS is an automated decision support system developed in a collaboration between Stanford University and the U.S. Department of Veterans Affairs (VA) to increase guideline-adherent prescribing and to change physician behavior., The use of a computer-based decision support system facilitates primary care physicians' management of chronic pain., The use of a CBDS system may improve the ability of PCPs to manage chronic pain and may also facilitate screening of consults to optimize specialist utilization.[SEP]Relations: Chronic pain has relations: phenotype_phenotype with Pain, phenotype_phenotype with Pain, disease_phenotype_positive with glycogen storage disease, disease_phenotype_positive with glycogen storage disease, disease_phenotype_positive with Sjogren syndrome, disease_phenotype_positive with Sjogren syndrome, disease_phenotype_positive with Machado-Joseph disease, disease_phenotype_positive with Machado-Joseph disease, disease_phenotype_positive with Loeys-Dietz syndrome, disease_phenotype_positive with Loeys-Dietz syndrome. Definitions: chronic pain defined as following: Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain..", "label": "yes"}
{"id": "converted_1580", "sentence1": "Do Conserved noncoding elements act as enhancers?", "sentence2": "The aCNEs are rich in tissue-specific enhancers, Transgenic zebrafish assay of some human CNE enhancers that have been lost in teleosts, Conserved noncoding elements (CNEs) in vertebrate genomes often act as developmental enhancers,, In all four cases where the zebra fish and human CNE display a similar expression pattern in zebra fish, the human CNE also displays a similar expression pattern in mouse. This suggests that the endogenous enhancer activity of ∼30% of human CNEs can be determined from experiments in zebra fish, If these ancient CNEs are indeed enhancers directing tissue-specific expression of Hox genes, divergence of their sequences in vertebrate lineages might have led to altered expression patterns and presumably the functions of their associated Hox genes., Comparisons of noncoding sequences of the elephant shark and human Hox clusters have identified a large number of conserved noncoding elements (CNEs), which represent putative cis-regulatory elements that may be involved in the regulation of Hox genes., Animal genomes possess highly conserved cis-regulatory sequences that are often found near genes that regulate transcription and development., We test 42 of our PCNEs in transgenic zebrafish assays--including examples from vertebrates and amphioxus--and find that the majority are functional enhancers., The genomes of vertebrates, flies, and nematodes contain highly conserved noncoding elements (CNEs). CNEs cluster around genes that regulate development, and where tested, they can act as transcriptional enhancers., , we identified 17 highly conserved noncoding elements, 9 of which revealed specific acetylation marks in chromatin-immunoprecipitation and microarray (ChIP-chip) assays performed across 250 kb of the Lmo2 locus in 11 cell types covering different stages of hematopoietic differentiation. All candidate regulatory regions were tested in transgenic mice. An extended LMO2 proximal promoter fragment displayed strong endothelial activity, while the distal promoter showed weak forebrain activity. Eight of the 15 distal candidate elements functioned as enhancers,, Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control., HCNEs of both human and zebrafish function as specific developmental enhancers in zebrafish., several transcriptional enhancers are conserved between amphioxus and vertebrates--a very wide phylogenetic distance., We recently described GRBs in vertebrates, where most HCNEs function as enhancers, Besides developmental regulators that are likely targets of HCNE enhancers, We identify and characterize highly conserved noncoding elements flanking the TNF gene, which undergo activation-dependent intrachromosomal interactions. These elements, hypersensitive site (HSS)-9 and HSS+3 (9 kb upstream and 3 kb downstream of the TNF gene, respectively), contain DNase I hypersensitive sites in naive, T helper 1, and T helper 2 primary T cells. Both HSS-9 and HSS+3 inducibly associate with acetylated histones, indicative of chromatin remodeling, bind the transcription factor nuclear factor of activated T cells (NFAT)p in vitro and in vivo, and function as enhancers, We used the sequence signatures identified by this approach to successfully assign tissue-specific predictions to approximately 328,000 human-mouse conserved noncoding elements in the human genome. By overlapping these genome-wide predictions with a data set of enhancers validated in vivo, in transgenic mice, we were able to confirm our results with a 28% sensitivity and 50% precision., Fish-mammal genomic comparisons have proved powerful in identifying conserved noncoding elements likely to be cis-regulatory in nature, and the majority of those tested in vivo have been shown to act as tissue-specific enhancers associated with genes involved in transcriptional regulation of development., uncovered two anciently conserved noncoding sequences (CNS) upstream of COUP-TFII (CNS-62kb and CNS-66kb). Testing these two elements using reporter constructs in liver cells (HepG2) revealed that CNS-66kb, but not CNS-62kb, yielded robust in vitro enhancer activity.[SEP]Relations: Protein S human has relations: drug_drug with Nonacog beta pegol, drug_drug with Nonacog beta pegol, drug_drug with Resveratrol, drug_drug with Resveratrol, drug_drug with Antihemophilic factor, human recombinant, drug_drug with Antihemophilic factor, human recombinant, drug_drug with Antihemophilic Factor (Recombinant), PEGylated, drug_drug with Antihemophilic Factor (Recombinant), PEGylated. central nervous system has relations: anatomy_protein_present with NONO, anatomy_protein_present with NONO. Definitions: sequences defined as following: The sequence of nucleotide residues along a DNA chain.. 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.. liver cells defined as following: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.. zebrafish defined as following: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research.. regulatory regions defined as following: Nucleic acid sequences involved in regulating the expression of genes.. vertebrate defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes.. DNase I defined as following: Catalysis of the endonucleolytic cleavage of DNA to 5'-phosphodinucleotide and 5'-phosphooligonucleotide end products. [EC:3.1.21.1]. 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.. aCNEs defined as following: A chronic neuropathic pain syndrome of the abdominal wall caused by entrapment of anterior cutaneous branches of 7 to 12th intercostal nerves along the lateral border of the anterior rectus abdominis fascia.. TNF gene defined as following: This gene is involved in apoptosis, cell growth and cell proliferation. It also plays a role in immune and inflammatory responses.. 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.. Lmo2 defined as following: Human LMO2 wild-type allele is located in the vicinity of 11p13 and is approximately 34 kb in length. This allele, which encodes rhombotin-2 protein, is involved in red blood cell development through the modulation of transcription by RNA polymerase II.. COUP-TFII defined as following: COUP transcription factor 2 (414 aa, ~46 kDa) is encoded by the human NR2F2 gene. This protein is involved in the mediation of transcription.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. flies defined as following: An order of the class Insecta. Wings, when present, number two and distinguish Diptera from other so-called flies, while the halteres, or reduced hindwings, separate Diptera from other insects with one pair of wings. The order includes the families Calliphoridae, Oestridae, Phoridae, SARCOPHAGIDAE, Scatophagidae, Sciaridae, SIMULIIDAE, Tabanidae, Therevidae, Trypetidae, CERATOPOGONIDAE; CHIRONOMIDAE; CULICIDAE; DROSOPHILIDAE; GLOSSINIDAE; MUSCIDAE; TEPHRITIDAE; and PSYCHODIDAE. The larval form of Diptera species are called maggots (see LARVA).. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. transgenic mice defined as following: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.. pleiotropic genes defined as following: A single gene that influences several distinct and seemly unrelated phenotypic outcomes.. Hox genes defined as following: Genes that encode highly conserved TRANSCRIPTION FACTORS that control positional identity of cells (BODY PATTERNING) and MORPHOGENESIS throughout development. Their sequences contain a 180 nucleotide sequence designated the homeobox, so called because mutations of these genes often results in homeotic transformations, in which one body structure replaces another. The proteins encoded by homeobox genes are called HOMEODOMAIN PROTEINS.. human defined as following: Members of the species Homo sapiens.. genomes defined as following: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.. enhancer defined as following: A 50-150bp DNA sequence that increases the rate of transcription of coding sequences. It may be located at various distances and in either orientation upstream from, downstream from or within a structural gene. When bound by a specific transcription factor it increases the levels of expression of the gene, but is not sufficient alone to cause expression. Distinguished from a promoter, that is alone sufficient to cause expression of the gene when bound.. 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..", "label": "yes"}
{"id": "converted_225", "sentence1": "Is it safe to take isotretinoin during pregnancy?", "sentence2": "Isotretinoin is a remarkably effective drug for severe, recalcitrant acne vulgaris., a number of important adverse effects were reported, even the most recent pregnancy prevention program (iPledge) is no more successful than prior programs; there will likely always be a small number of female patients becoming pregnant while receiving isotretinoin for acne vulgaris., Isotretinoin has revolutionized the management of acne vulgaris., The adverse effect(s) that led to patients stopping isotretinoin were cheilitis (22 patients), mood change (13), tiredness (12), eczema (6) and pregnancy (2)., Downregulation of FGFR2b-signaling by isotretinoin explains its therapeutic effect in acne. Downregulation of FGFR2b-signaling during the first trimester of pregnancy disturbs branched morphogenesis and explains retinoid embryotoxicity., The isotretinoin, a 13-cis-retinoic acid, has revolutionized the management of severe treatment-resistant acne and it has been widely used for a range of dermatological conditions, in 90% of the time in young women between 13 and 45 years of age. This agent has severe teratogenic effects, as serious craniofacial, cardiovascular, thymic and central nervous system malformations., malformations is 3-5%, but it increases to almost 30% in women exposed to isotretinoin during the first trimester of pregnancy. Generally, patients in treatment with isotretinoin avoid eventual pregnancy during assumption and, after its stopping, fertility and foetal development are normal once circulating isotretinoin levels return to normal., After 3 months of pharmacological wash out, patient become pregnant and manifested this severe malformation. Woman interrupted gestation, by labour induction., Clindamycin phosphate 1.2% together with tretinoin 0.025% as a gel (CTG) is a topical formulation of a fixed and stable combination approved by the FDA for the treatment of acne vulgaris in patients 12 years of age or older., Safety of CTG use in pregnancy has not been established., To estimate the population-based incidence rates of pregnancy, spontaneous and elective abortions, and birth defects associated with isotretinoin use, and to determine predictors of pregnancy while on isotretinoin, Pregnancies, spontaneous and elective abortions, and birth defects were identified using procedure codes and medical diagnoses., 90 women who became pregnant while on the drug, 76 terminated the pregnancy (84%), three had a spontaneous abortion (3%), two had trauma during delivery resulting in neonatal deaths (2%) and nine had a live birth (10%). Among the live births, only one had a congenital anomaly of the face and neck (11%)., elective abortion rates were also much higher in our study., Topical antibiotics, isotretinoin or systemic antibiotics are usually used for acne therapy. However, isotretinoin cannot be used during pregnancy because it can cause significant birth defects while systemic antibiotics can have adverse side effects such as gastrointestinal irritation, photosensitivity and tetracycline sensitivity., Isotretinoin has been used to treat acne since 1982. Its current indications in the package insert are limited and many physicians still feel uncomfortable prescribing it because of its side effects., Aside from its teratogenic effect, isotretinoin is a safe and excellent drug for acne therapy. I, a pregnancy test in females., Vitamin A and its derivatives, retinoic acid, tretinoin and isotretinoin, are currently used in dermatological treatments. The administration of high doses of this vitamin provokes congenital malformations in mice: cleft palate, maxillary and mandibular hypoplasia and total or partial fusion of the maxillary incisors., Twelve 60-day-old female Mus musculus were divided into two groups on the 7th day of pregnancy: treated group--1 mg isotretinoin per kg body weight, dissolved in vegetable oil, was administered from the 7th to the 13th day of pregnancy; control group--vegetable oil in equivalent volume was administered orally for the same period. On the 16th day of pregnancy, the females were sacrificed, the fetuses were removed and their heads amputated., The results showed that both groups had closed palates with no reminiscence of epithelial cells; however, the first molar germs of the isotretinoin-treated animals showed delayed development compared to the control animals., Isotretinoin (13-cis-RA) is teratogenic in all species examined; based on administered dose, humans appear most sensitive, followed by (in order or decreasing sensitivity) monkey, rabbit, hamster, mouse, and rat., Based on embryonic delivered dose, we suggest that 13-cis-RA is an equipotent teratogen in hamster and rabbit., its safety in humans is occasionally questioned because oral ingestion of retinoids at therapeutic levels is known to entail teratogenic risks., topical tretinoin is not a potential human developmental toxicant., Teratogenicity of vitamin A was firstly detected in experimental animals in 1953. Nearly 30 years later, teratogenicity of vitamin A analogue-isotretinoin was reported in humans. Isotretinoin induces serious birth defects of craniofacial and central nervous system, cardiovascular system and thymic malformations--in about 25% of babies exposed during the first trimester of their prenatal development., high vitamin A intake in pregnant woman: Women who use daily vitamin A supplements during early pregnancy have approximately a two-fold increased risk of giving birth to a malformed baby., Vitamin A started to affect development between doses 0.3-0.3 microm [corrected] per embryo. Malformations of head, extremities and heart were detected similarly like in laboratory mammals and in man, the minimal embryotoxic doses of vitamin A in mammals were estimated to be between 0.1-1 mg/kg of maternal weight, Human epidemiological studies have proved teratogenicity of vitamin A after daily doses 25,000 i.u.-8.3 mg (0.13 mg/kg)- and reduction of its maximum intake has been recommended to 10,000 i.u. per day (0.05 mg/kg). The results about teratogenicity of vitamin A achieved in the chick embryo are in agreement with such a recommendation. Intake of vitamin A in the food is sufficient for pregnant woman in common Czech population. Therefore, an artificial supplementation of vitamin A brings risk of overdosage. If supplementation by vitamin A is unavoidable during pregnancy, B-carotene should be preferred., a teratogenic dosing regimen with 13-cis-RA [Hummler et al. (1994) Teratology 50:184-193]., plasma AUC values of all-trans-RA were 2- to 7-fold higher after all-trans-RA administration (present study) than after dosing with the teratogenic dose of 13-cis-RA. These results strengthen our recent suggestion that the teratogenic effects induced in cynomolgus monkeys by 13-cis-RA treatment cannot solely result from the action of all-trans-RA, but may involve 13-cis-RA and 13-cis-4-oxo-RA, which could act directly or function as transport vehicle., VITA, among others, is involved in the process of morphogenesis. In contrast, synthetic derivatives of VITA, specifically Tigasone (etretinate, TIG) and Roaccutane (isotretinoin, ROA), are regarded as major teratogens., A biphasic maximal inhibition was present at 1 microM concentrations when the retinoids VITA, TIG and ROA were added for 16 h (52, 58 and 57%, respectively; P < 0.01 by one-way analysis of variance). In contrast, the addition of the three retinoids at 1 microM concentrations for 16 h had no significant effect on HCG secretion by placental explants of 11-13 weeks gestational age., Inhibition of HCG secretion by retinoids may contribute either directly or indirectly to their teratogenicity., Isotretinoin is a potent retinoic acid used in the treatment of skin disorders. Though very effective, it is teratogenic if administered during pregnancy, and its teratogenic effect may be related to the normal activity of retinoids as signalling molecules in the embryo., defects that includes heart defects, by inhibiting the migration of neural crest cells., Proliferation in heart tissue of whole embryo cultures was inhibited in medium with 10(-6) M isotretinoin to 62% of the control level in myocardium., The results suggest multiple effects of retinoids on growth, morphogenesis, and differentiation of early cardiac tissue, and are discussed in relation to the potential role of retinoids in early embryogenesis., Oral administration of 400 mg/kg of 13-cis retinoic acid to 9 day pregnant mice gives rise to important maxillofacial malformations. The first manifestation of teratogenic effect is an increase of density of cell death arising in the dorsal part of the first two branchial arches at day 9.5. These two arches become hypoplastic at days 10 and 11, and the preskeletal anlagen appear too late in comparison to control embryos. Meckel's cartilage is too curvilinear and medially situated. Pre-ossicular and pre-mandibular blastemata develop with spatial distortions which are well analyzable at days 16 and 17, Isotretinoin (13-cis-retinoic acid, Accutane) increases the risk of major congenital malformations in infants exposed to isotretinoin during pregnancy. However, there have been no epidemiologic reports to date on the effect of a subsequent pregnancy after discontinuation of isotretinoin., analysis of pregnancy case reports from patients in whom conception occurred after isotretinoin treatment had been discontinued, spontaneous and missed abortions from all pregnancies was 9.1% (eight patients), and the incidence rate of congenital malformation among the live births was 5.0% (four patients)., were not significantly different from the rates reported for women of reproductive age in the general population. In addition, the malformations reported were not characteristic of retinoic acid-induced congenital anomalies., Keratolenticular dysgenesis (Peters' anomaly) was induced in mice by exposure to the human teratogens, ethanol or 13-cis retinoic acid (isotretinoin, Accutane). Acute teratogen exposure on the seventh day of gestation (corresponding to the third week of human gestation) resulted in an eye malformation incidence of 46% to 100% in day 14 fetuses, This secondary effect on neural crest derivatives is exhibited in the adult animals as corneal opacities associated with defects in Descemet's membrane and endothelium, and anterior polar cataracts., 13-cis-retinoic acid (13-cis-RA, or isotretinoin) is responsible for various craniofacial malformations in the rodent and human embryo., In whole embryo culture, 13-cis-RA caused significant overall embryonic growth retardation, especially in the primary and secondary palatal processes., subsequent cell growth was decreased at concentrations of 13-cis-RA greater than 1 X 10(-5) M. After a 40-hr treatment period, labeling indices in retinoid-treated cells were significantly lower than control values (25% compared with 40%). Retinoic acid also caused a significant, concentration-dependent decrease in 3H-thymidine incorporation. The inhibitory effect of 13-cis-RA on proliferation of oral-nasal mesenchymal cells appears to be related to the production of craniofacial malformations., Reports of adverse human pregnancy outcomes including cleft palate have increased as the clinical use of isotretinoin (13-cis-retinoic acid) and other retinoic acid (RA) derivatives have increased, but the mechanisms by which their effects are exerted are not understood., In shelves exposed to EGF and trans-RA early in their development, DNA synthesis appears to terminate prematurely as compared to shelves cultured in control media, and this effect is accompanied by excessive mesenchymal extracellular space expansion. Exposure of shelves to EGF alone is sufficient to block degeneration and induce hyperplasia of the medial epithelial cells but does not induce other ultrastructural changes seen with both EGF and RA. The observed alterations in medial cell morphology could interfere with adhesion of the palatal shelves and may play a role in retinoid-induced cleft palate in the human embryo., Recent clinical observations strongly suggest that isotretinoin [13-cis-retinoic acid (cis RA)] is a human teratogen causing primarily heart and craniofacial malformations including ear and palatal defects., Our results demonstrate that labeled cis RA enters the tissues of the embryo both in vivo and in vitro. Cis RA inhibited proliferation of the frontonasal mesenchyme cells in primary culture with 31% inhibition occurring at 2 X 10(-5) M cis RA., Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants. A subset of 36 of the 154 pregnancies was observed prospectively., Exposure to isotretinoin was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5)., It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations.[SEP]Relations: Isotretinoin has relations: contraindication with heart disease, contraindication with heart disease, contraindication with hepatitis, contraindication with hepatitis, contraindication with anxiety disorder, contraindication with anxiety disorder, contraindication with kidney disease, contraindication with kidney disease, contraindication with liver disease, contraindication with liver disease. Definitions: epithelial cells defined as following: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.. etretinate defined as following: An oral retinoid used in the treatment of keratotic genodermatosis, lichen planus, and psoriasis. Beneficial effects have also been claimed in the prophylaxis of epithelial neoplasia. The compound may be teratogenic.. RA defined as following: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.. isotretinoin defined as following: A topical dermatologic agent that is used in the treatment of ACNE VULGARIS and several other skin diseases. The drug has teratogenic and other adverse effects.. cardiovascular defined as following: The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body.. Retinoic acid defined as following: An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).. malformation defined as following: Malformations of organs or body parts during development in utero.. Peters' anomaly defined as following: A form of anterior segment dysgenesis in which abnormal cleavage of the anterior chamber occurs. Peters anomaly is characterized by central, paracentral, or complete corneal opacity. [HPO:probinson]. retinoids defined as following: A group of tetraterpenes, with four terpene units joined head-to-tail. Biologically active members of this class are used clinically in the treatment of severe cystic ACNE; PSORIASIS; and other disorders of keratinization.. ethanol defined as following: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.. 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.. endothelium defined as following: A layer of epithelium that lines the heart, blood vessels (ENDOTHELIUM, VASCULAR), lymph vessels (ENDOTHELIUM, LYMPHATIC), and the serous cavities of the body.. skin disorders defined as following: Diseases involving the DERMIS or EPIDERMIS.. HCG defined as following: A sialoglycoprotein hormone secreted by the placenta and maintains the corpus luteum at the beginning of the gestation period.. palatal defined as following: The structure that forms the roof of the mouth. It consists of the anterior hard palate (PALATE, HARD) and the posterior soft palate (PALATE, SOFT).. Clindamycin phosphate defined as following: The phosphate salt form of clindamycin, a semi-synthetic, chlorinated broad spectrum antibiotic produced by chemical modification of lincomycin. Clindamycin phosphate is used in topical preparations.. trauma defined as following: Nurses in this specialty provide emergency care to patients of all ages. These nurses work to maintain vital signs and prevent complications and death. 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.. 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.. dorsal defined as following: Pertaining to the back or upper surface of the body; opposite of ventral.. corneal defined as following: The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous CORNEAL EPITHELIUM; BOWMAN MEMBRANE; CORNEAL STROMA; DESCEMET MEMBRANE; and mesenchymal CORNEAL ENDOTHELIUM. It serves as the first refracting medium of the eye. It is structurally continuous with the SCLERA, avascular, receiving its nourishment by permeation through spaces between the lamellae, and is innervated by the ophthalmic division of the TRIGEMINAL NERVE via the ciliary nerves and those of the surrounding conjunctiva which together form plexuses. (Cline et al., Dictionary of Visual Science, 4th ed). rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. photosensitivity defined as following: Increased sensitivity of the skin to light exposure.. acne vulgaris defined as following: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors.. thymic defined as following: A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.. deaths defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. monkey defined as following: Any haplorhine primate not belonging to the family Tarsiidae, Hylobatidae, Pongidae, or Hominidae; this does not correspond to any taxon. This group is divided into Old World monkeys (Cercopithecidae) and New World monkeys (Callitrichidae and Cebidae). Many types are used as an experimental model for human disease and drug testing.. Cis defined as following: Cytokine-inducible SH2-containing protein (258 aa, ~29 kDa) is encoded by the human CISH gene. This protein is involved in the modulation of signal transduction.. rodent defined as following: A mammalian order which consists of 29 families and many genera.. Mus musculus defined as following: The common mouse species, Mus musculus.. head defined as following: A projection on the end of an object. neural crest cells defined as following: Neuroectodermal cells of the neural crest. They differentiate into various cell types during EMBRYOGENESIS including craniofacial MESENCHYME; ENDOCRINE CELLS; MELANOCYTES and PERIPHERAL NERVOUS SYSTEM.. EGF defined as following: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.. eczema defined as following: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed).. labour defined as following: Uterine contractions resulting in cervical change (dilation and/or effacement). (reVITALize). cystic acne defined as following: A severe type of acne characterized by the formation of cysts enclosing a mixture of keratin and sebum. [PMID:9212761]. mammals defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. vegetable oil defined as following: oils derived from plants or plant products.. humans defined as following: Members of the species Homo sapiens.. embryo defined as following: An organism in its initial stage of development following fertilization. The human embryonic period lasts approximately eight weeks, during which time organogenesis takes place.. 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.. craniofacial defined as following: refers to the bones of the skull and face.. cartilage defined as following: A non-vascular form of connective tissue composed of CHONDROCYTES embedded in a matrix that includes CHONDROITIN SULFATE and various types of FIBRILLAR COLLAGEN. There are three major types: HYALINE CARTILAGE; FIBROCARTILAGE; and ELASTIC CARTILAGE.. heart defects defined as following: Developmental abnormalities involving structures of the heart. These defects are present at birth but may be discovered later in life..", "label": "no"}
{"id": "converted_4038", "sentence1": "Is the process of DNA loop-extrusion independent of ATP?", "sentence2": "The DNA-organizing mechanism of condensin depends on the energy of ATP hydrolysis but how this activity specifically promotes proper compaction and segregation of chromosomes during mitosis remains poorly understood., We suggest that loading and translocation are mediated by conformational changes in cohesin's hinge driven by cycles of ATP hydrolysis., Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases., Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA. , Each TAD emerges from multiple loops dynamically formed through extrusion, contrary to typical illustrations of single static loops. , However, the model requires a motor to generate the loops, and although cohesin is a strong candidate for the extruding factor, a suitable motor protein (or a motor activity in cohesin itself) has yet to be found. Here we explore a new hypothesis: that there is no motor, and thermal motion within the nucleus drives extrusion., We observed that a single condensin complex is able to extrude tens of kilobase pairs of DNA at a force-dependent speed of up to 1500 base pairs per second, using the energy of adenosine triphosphate hydrolysis, Our model explains what can be the driving force of chromatin loop extrusion and how it can be ensured that loops grow quickly and in a good direction. In addition, the supercoiling-driven loop extrusion mechanism is consistent with earlier explanations proposing why TADs flanked by convergent CTCF binding sites form more stable chromatin loops than TADs flanked by divergent CTCF binding sites., Oligomerization and ATP stimulate condensin-mediated DNA compaction., Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA., DNA compaction by cohesin requires adenosine triphosphate (ATP) hydrolysis and is force sensitive., The identification and quantification of further initiation steps--ATP binding and extrusion of an initial DNA loop--allowed us to deduce a complete kinetic reinitiation scheme., In support of this model, single-molecule imaging experiments indicate that Saccharomyces cerevisiae condensin complexes can extrude DNA loops in an ATP-hydrolysis-dependent manner in vitro., These structures depend on cohesin, a ring-shaped DNA-entrapping adenosine triphosphatase (ATPase) complex that has been proposed to form loops by extrusion., Loop formation and maintenance depend on cohesin's ATPase activity and on NIPBL-MAU2, but not on topological entrapment of DNA by cohesin.[SEP]Relations: Adenosine phosphate has relations: drug_protein with PRKAG2, drug_protein with PRKAG2, drug_protein with PRKAG2, drug_protein with PRKAG2, drug_protein with PRKAG3, drug_protein with PRKAG3, drug_protein with PRKAG3, drug_protein with PRKAG3, drug_protein with PRKAG1, drug_protein with PRKAG1. Definitions: 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.. CTCF defined as following: CCN family member 2 (349 aa, ~38kDa) is encoded by the human CCN2 gene. This protein plays a role in the promotion of proliferation and differentiation of chondrocytes and also mediates heparin- and divalent cation-dependent cell adhesion in many different cell types.. adenosine triphosphate defined as following: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.. hydrolysis defined as following: The process of cleaving a chemical compound by the addition of a molecule of water.. DNA loop defined as following: A higher order chromatin structure above the level of the chromatin fiber. The organization of chromatin into loops permits the partitioning of chromatin into topologically independent domains, and is thought to facilitate its compartmentation into functionally independent regions.. 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).. binding sites defined as following: The parts of a macromolecule that directly participate in its specific combination with another molecule.. TADs defined as following: Tietz syndrome is a genetic hypopigmentation and deafness syndrome characterized by congenital profound bilateral sensorineural hearing loss and generalized albino-like hypopigmentation of skin, eyes and hair.. ATP defined as following: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter..", "label": "yes"}
{"id": "converted_459", "sentence1": "Have mutations in the GARS gene been identified to cause Charcot-Marie-Tooth Disease Type 2D (CMT2D)?", "sentence2": "Charcot-Marie-Tooth disease type 2D is a hereditary axonal and glycyl-tRNA synthetase (GARS)-associated neuropathy that is caused by a mutation in GARS. , Mutations in the GARS gene cause Charcot-Marie-Tooth 2D and distal spinal muscular atrophy type V - allelic disorders characterized by predominantly distal upper extremity weakness and atrophy, typically beginning during the second decade of life. , Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS)., The 13 genes known to be associated with the CMT2 subtypes are KIF1B (CMT2A1), MFN2 (CMT2A2), RAB7A (formerly RAB7) (CMT2B), LMNA (CMT2B1), MED25 (CMT2B2), TRPV4 (CMTC), GARS (CMT2D), NEFL (CMT2E/1F), HSPB1 (CMT2F), MPZ (CMT2I/J), GDAP1 (CMT2H/K), HSPB8 (CMT2L), and AARS (CMT2N). , The diagnosis of GARS-associated axonal neuropathy is based on clinical findings, electromyography (EMG), and molecular genetic testing of GARS, encoding glycyl-tRNA synthetase., Sporadic juvenile muscular atrophy of the distal upper extremity or Hirayama's disease (HD) and autosomal dominant motor distal neuronopathy/axonopathy (CMT2D/dSMA-V), produced by glycyl-tRNA synthetase (GARS) gene mutations, share some clinical features including: young age of onset, predilection for the distal upper extremity, asymmetry, sparing of proximal muscles and unusual cold sensitivity. , Distal hereditary motor neuropathy type V (dHMN-V) and Charcot-Marie-Tooth syndrome (CMT) type 2 presenting with predominant hand involvement, also known as CMT2D and Silver syndrome (SS) are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) and in the glycyl-tRNA synthetase encoding (GARS) genes. , We previously implicated mutations in the gene encoding glycyl-tRNA synthetase (GARS) as the cause of CMT2D and dSMA-V., Of the many inherited Charcot-Marie-Tooth peripheral neuropathies, type 2D (CMT2D) is caused by dominant point mutations in the gene GARS, encoding glycyl tRNA synthetase (GlyRS). , Missense mutations in the glycyl-tRNA synthetase (GARS) gene have been recently reported in families with either dHMN-V, CMT2D, or both., Based on the presence or absence of sensory changes, the disease phenotype was initially defined as distal spinal muscular atrophy type V (dSMA-V) in three families, Charcot-Marie-Tooth disease type 2D (CMT2D) in a single family, and as either dSMA-V or CMT2D in patients of another large family. Linkage to chromosome 7p15 and the presence of disease-associated heterozygous GARS mutations have been identified in patients from each of the five studied families. [SEP]Relations: Charcot-Marie-Tooth disease has relations: disease_protein with GARS1, disease_protein with GARS1, disease_protein with GARS1, disease_protein with GARS1, disease_protein with GARS1, disease_protein with GARS1, disease_protein with GARS1, disease_protein with GARS1, disease_protein with MTMR2, disease_protein with MTMR2. Definitions: muscular atrophy defined as following: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation.. glycyl tRNA synthetase defined as following: An enzyme that activates glycine with its specific transfer RNA. EC 6.1.1.14.. 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.. CMT2B2 defined as following: An axonal Charcot-Marie-Tooth peripheral sensorimotor polyneuropathy that has been described in a large consanguineous Costa Rican family of Spanish ancestry. Onset occurs in adulthood (between 26 and 42 years of age) with symmetric moderate to severe weakness of the distal muscles, predominantly affecting the lower extremities. Marked sensory deficits were also reported. Transmitted in an autosomal recessive manner and the disease-causing gene was mapped to chromosome 19q13.3 (MED25).. glycyl-tRNA synthetase defined as following: Human GARS1 wild-type allele is located in the vicinity of 7p14.3 and is approximately 39 kb in length. This allele, which encodes glycine-tRNA ligase protein, is involved in the synthesis of glycyl-tRNA. Mutation of the gene is associated with type 2D Charcot-Marie-Tooth disease and distal hereditary motor neuropathy, type Va.. NEFL defined as following: Neurofilament light polypeptide (543 aa, ~62 kDa) is encoded by the human NEFL gene. This protein is involved in the modulation of neuronal structure.. RAB7 defined as following: Human RAB7A wild-type allele is located in the vicinity of 3q21 and is approximately 89 kb in length. This allele, which encodes ras-related protein Rab-7a, plays a role in the localization and function of both endosomes and lysosomes. Mutation of the gene is associated with Charcot-Marie-Tooth disease 2B.. CMT2D defined as following: Charcot-Marie-Tooth disease inherited in an autosomal dominant pattern. It is caused by mutations in the GARS gene. It results in axonal peripheral neuropathy.. KIF1B defined as following: Kinesin-like protein KIF1B (1816 aa, ~204 kDa) is encoded by the human KIF1B gene. This protein plays a role in intercellular transport of organelles and vesicles.. SS defined as following: Supernumerary mandibular right first primary molar
. neuropathy defined as following: A disorder affecting the cranial nerves or the peripheral nervous system. It manifests with pain, tingling, numbness, and muscle weakness. It may be the result of physical injury, toxic substances, viral diseases, diabetes, renal failure, cancer, and drugs.. Charcot-Marie-Tooth disease defined as following: A hereditary motor and sensory neuropathy transmitted most often as an autosomal dominant trait and characterized by progressive distal wasting and loss of reflexes in the muscles of the legs (and occasionally involving the arms). Onset is usually in the second to fourth decade of life. This condition has been divided into two subtypes, hereditary motor and sensory neuropathy (HMSN) types I and II. HMSN I is associated with abnormal nerve conduction velocities and nerve hypertrophy, features not seen in HMSN II. (Adams et al., Principles of Neurology, 6th ed, p1343). TRPV4 defined as following: Transient receptor potential cation channel subfamily V member 4 (871 aa, ~98 kDa) is encoded by the human TRPV4 gene. This protein plays a role in the modulation of calcium transport.. CMTC defined as following: A congenital vascular malformation that presents as localized or generalized erythematous-telangiectatic lesions with a reticular pattern; the lesions are almost always present at birth or develop in the first days of life. Cutis marmorata telangiectatica congenita (CMTC) appears as marble-like pattern (mottling) on the surface of the skin. In contrast to cutis marmorata, the marbling is more severe and always visible. [PMID:22483320, PMID:25864701]. CMT2F defined as following: A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy with symmetric weakness primarily occurring in the lower limbs and reaching the arms only after 5 to 10 years, occasional and predominantly distal sensory loss and reduced tendon reflexes. Presents with gait anomaly between the first and sixth decade and early onset is generally associated to a more severe phenotype that may include foot drop.. Berardinelli-Seip Congenital Lipodystrophy 2 defined as following: It is caused by mutation of gene encoding seipin (BSCL2).. MFN2 defined as following: Mitofusin-2 (757 aa, ~86 kDa) is encoded by the human MFN2 gene. This protein is involved in both mitochondrial fusion and GTP hydrolysis.. CMT2B1 defined as following: An axonal Charcot-Marie-Tooth peripheral sensorimotor polyneuropathy. It has been described exclusively in families originating from North-Western Africa. Onset occurs in the second decade of life. The disease course and severity are variable, even between affected members of the same family. In general, the disease manifests as distal muscle weakness and atrophy that progress gradually to the proximal muscles. Caused by a p.R644C missense mutation in the lamin A/C protein (encoded by the LMNA gene, 1q22). Transmitted in an autosomal recessive manner.. dHMN-V defined as following: A rare autosomal dominant distal hereditary motor neuropathy disease characterized by muscle weakness and wasting predominantly affecting the hands, in particular the thenar and first dorsal interosseus muscles, and/or marked foot deformity and gait disturbance. Sensation is normal, although reduced response to vibration has been described. The disease is slowly progressive with an age of onset within the first few decades of life.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. point mutations defined as following: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.. autosomal defined as following: Any chromosome other than a sex chromosome. [GOC:mah]. RAB7A defined as following: This gene is involved in the trafficking of endosomes and lysosomes.. LMNA defined as following: Prelamin-A/C (664 aa, ~74 kDa) is encoded by the human LMNA gene. This protein is involved in the framework required for the nuclear envelope and in chromatin interactions.. HSPB1 defined as following: Heat shock protein beta-1 (205 aa, ~23 kDa) is encoded by the human HSPB1 gene. This protein is involved in protein denaturation and the cellular response to oxidative stress.. CMT2L defined as following: A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy. In the single family reported to date, onset is between 15 and 33 years. Patients present with a symmetric distal weakness of legs and occasionally of the hands, absent or reduced tendon reflexes, distal legs sensory loss and frequently a pes cavus. Progression is slow.. 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.. Silver syndrome defined as following: A complex hereditary spastic paraplegia with characteristics of progressive spastic paraplegia, upper and lower limb muscle atrophy, hyperreflexia, extensor plantar responses, pes cavus and occasionally impaired vibration sense.. HSPB8 defined as following: Heat shock protein beta-8 (196 aa, ~22 kDa) is encoded by the human HSPB8 gene. This protein plays a role in the regulation of autophagy and as a protein chaperone.. atrophy defined as following: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.. HD defined as following: A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen.. CMT2A1 defined as following: An autosomal dominant sub-type of Charcot-Marie-Tooth disease caused by mutation(s) in the KIF1B gene, encoding kinesin-like protein KIF1B.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. Charcot-Marie-Tooth Disease Type 2D defined as following: Charcot-Marie-Tooth disease inherited in an autosomal dominant pattern. It is caused by mutations in the GARS gene. It results in axonal peripheral neuropathy..", "label": "yes"}
{"id": "converted_1695", "sentence1": "Is calcium overload involved in the development of diabetic cardiomyopathy?", "sentence2": "High-glucose treatment resulted in increased intracellular calcium ([Ca2+]i) which was mobilized to the mitochondria. Concomitant intra-mitochondrial calcium ([Ca2+]m) increase resulted in enhanced reactive oxygen and nitrogen species generation. These events led to mitochondrial dysfunction and apoptosis., The novel findings of the study reveal that high glucose induces apoptosis by both mitochondria-dependent and independent pathways via concomitant rise in intracellular calcium., Diabetes-induced myocardial dysfunction has been attributed, in part, to calcium overload within individual myocytes., It seems that intracellular calcium overload is intimately involved in the development of diabetic cardiomyopathy;, BACKGROUND: It has been suggested that intracellular Ca2+ overload in cardiac myocytes leads to the development of diabetic cardiomyopathy., The results from the alloxan-rat model of diabetes support the view that membrane abnormalities with respect to Ca2+ handling may lead to the occurrence of intracellular Ca2+ overload and the development of diabetic cardiomyopathy., It seems that intracellular calcium overload is intimately involved in the development of diabetic cardiomyopathy; however, a concentrated research effort is required to understand the primary biochemical lesion in the pathogenesis of cardiac dysfunction in diabetes., It has been suggested that the occurrence of an intracellular Ca2+ overload may result in the development of diabetic cardiomyopathy, which is associated with depletion of high-energy phosphate stores and a derangement of ultrastructure and cardiac dysfunction.[SEP]Relations: cardiomyopathy diabetes deafness has relations: disease_disease with syndromic disease, disease_disease with syndromic disease. Abnormality of mitochondrial metabolism has relations: disease_phenotype_positive with reticular dysgenesis, disease_phenotype_positive with reticular dysgenesis, disease_phenotype_positive with atherosclerosis-deafness-diabetes-epilepsy-nephropathy syndrome, disease_phenotype_positive with atherosclerosis-deafness-diabetes-epilepsy-nephropathy syndrome. Type I diabetes mellitus has relations: disease_phenotype_positive with sclerosing cholangitis, disease_phenotype_positive with sclerosing cholangitis, disease_phenotype_positive with multicentric osteolysis-nodulosis-arthropathy spectrum, disease_phenotype_positive with multicentric osteolysis-nodulosis-arthropathy spectrum. Definitions: calcium defined as following: A dietary supplement containing the mineral calcium.. cardiac myocytes defined as following: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).. mitochondria defined as following: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed). 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.. diabetic cardiomyopathy defined as following: Diabetes complications in which VENTRICULAR REMODELING in the absence of CORONARY ATHEROSCLEROSIS and hypertension results in cardiac dysfunctions, typically LEFT VENTRICULAR DYSFUNCTION. The changes also result in myocardial hypertrophy, myocardial necrosis and fibrosis, and collagen deposition due to impaired glucose tolerance.. diabetes defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.. mitochondrial dysfunction defined as following: A functional anomaly of mitochondria. [ORCID:0000-0001-5208-3432].", "label": "yes"}
{"id": "converted_3260", "sentence1": "Can leuprorelin acetate be used as androgen deprivation therapy?", "sentence2": "We investigated the health-related quality of life (HRQoL) of long-term prostate cancer patients who received leuprorelin acetate in microcapsules (LAM) for androgen-deprivation therapy (ADT)., Long-term ADT with LAM is a well-accepted, tolerated, effective, and low-burden treatment option for patients with advanced, hormone-sensitive PCa.[SEP]Relations: lymphangioleiomyomatosis has relations: disease_phenotype_positive with Cognitive impairment, disease_phenotype_positive with Cognitive impairment, disease_phenotype_positive with Ascites, disease_phenotype_positive with Ascites, disease_phenotype_positive with Restrictive ventilatory defect, disease_phenotype_positive with Restrictive ventilatory defect, disease_phenotype_positive with Macule, disease_phenotype_positive with Macule, disease_phenotype_positive with Seizure, disease_phenotype_positive with Seizure. Definitions: LAM defined as following: A multifocal neoplasm with perivascular epithelioid cell differentiation affecting almost exclusively females of child-bearing age. It is characterized by the presence of smooth muscle and epithelioid cells and by the proliferation of lymphatic vessels. Sites of involvement include the lungs, mediastinum, and the retroperitoneum. It usually presents with chylous pleural effusion or ascites.. prostate cancer defined as following: A primary or metastatic malignant tumor involving the prostate gland. The vast majority are carcinomas.. microcapsules defined as following: microscopic spheres of organic polymer or other material, usually used for slow release drug delivery or to protect orally administered agents from destruction in digestive tract; do not confuse with BACTERIAL CAPSULE.. ADT defined as following: A protein complex that possesses glutamyl-tRNA(Gln) amidotransferase activity, and therefore creates Gln-tRNA by amidating Glu-tRNA; usually composed of 3 subunits: A, B, and C. Note that the C subunit may not be required in all organisms. [GOC:mlg]. 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)..", "label": "yes"}
{"id": "converted_3938", "sentence1": "Is carpal tunnel syndrome a type of nerve entrapment?", "sentence2": " Carpal tunnel syndrome (CTS) is a common entrapment neuropathy, often requiring carpal tunnel release (CTR) surgery., Carpal tunnel syndrome (CTS) is an entrapment neuropathy accounting for up to 90% of nerve compression syndromes, Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy in humans. , Carpal tunnel syndrome (CTS) is the most common focal entrapment mononeuropathy, comprising medium nerve chronic inflammation and fibrosis., Carpal tunnel syndrome (CTS) is the most common nerve entrapment neuropathy which is the result of the compression of the median nerve in the wrist. , Dear sir, one of the most common entrapment neuropathy syndromes in clinical practice is \"Entrapment of median nerve in carpal tunnel\" also called \"Carpal tunnel syndrome (CTS)\" (Aydin et al., 2007; Huisstede et al., 2010)., BACKGROUND: Carpal tunnel syndrome (CTS) is the most common type of peripheral nerve entrapment and is a significant cause of morbidity., BACKGROUND: Carpal tunnel syndrome and ulnar nerve entrapment at the elbow are the most common entrapment neuropathies seen in adults., Entrapment neuropathies are of various types, but the most common type is carpal tunnel syndrome., Carpal Tunnel Syndrome and Other Entrapment Neuropathies., Unlike Guyon's canal syndrome, carpal tunnel syndrome (CTS) is the most common nerve entrapment of the upper extremity., chronic renal failure tend to develop peripheral nerve entrapment and carpal tunnel syndrome is the best-known peripheral entrapment neuropathy among them. Contrary to ca, Carpal tunnel syndrome (CTS) is a common form of peripheral nerve entrapment, which is observed due to compression of the median nerve at the level of the carpal tunnel in the wrist. Bifi, INTRODUCTION: Carpal tunnel syndrome (CTS) is considered a simple entrapment of the median nerve at the carp, Compressive neuropathy of the median nerve at the level of the carpal tunnel, known as carpal tunnel syndrome, is the most common entrapment neuropathy, affecting about 0.1-1% of the general population. Magne, BACKGROUND: Carpal tunnel syndrome (CTS) is entrapment of median nerve in carpal tunnel of th, Dear sir, one of the most common entrapment neuropathy syndromes in clinical practice is \"Entrapment of median nerve in carpal tunnel\" also called \"Carpal tunnel syndrome (CTS)\" (Aydin et al., 2007; Huisstede et al., 2010). This syndr, OBJECTIVE: Carpal tunnel syndrome (CTS) is a common median nerve entrapment neuropathy characterized by pain, paresthesias, diminished peripheral nerve conduction velocity (NCV) and maladaptive functional brain neuroplastici, Carpal tunnel syndrome (CTS), caused by entrapment of the median nerve in the carpal tunnel, impairs hand function including dexterous manipulation. The , This review focuses on three of the most common entrapment neuropathies in the upper limbs: carpal tunnel syndrome (median nerve entrapment at the wrist), cubital tunnel syndrome (ulnar nerve entrapment at the elbow), and radial tunnel syndrome (posterior interosseous nerve entrapment)., Electrodiagnostic (EDX) testing is usually an essential part of the evaluation of entrapment neuropathies, and examinations for the most common entrapment neuropathies, carpal tunnel syndrome and ulnar neuropathy at the elbow, constitute a significant part of the daily work in EDX laboratories., This study reviews the existing, more or less, detailed EDX criteria or practice parameters that are suggested by consensus groups in peer-reviewed journals for the most common entrapment neuropathies: carpal tunnel syndrome, ulnar neuropathy at the elbow, common peroneal (fibular) neuropathy at the fibular head, and tibial neuropathy at the tarsal tunnel., This report demonstrates that the Semmes-Weinstein monofilament test and nerve conduction studies can identify entrapment of the palmar cutaneous branch of the median nerve concomitant with carpal tunnel syndrome., Entrapment neuropathy of the palmar cutaneous branch of the median nerve concomitant with carpal tunnel syndrome: a case report., A case of the entrapment neuropathy of the palmar cutaneous branch of the median nerve, concomitant with carpal tunnel syndrome is presented., The entrapment syndromes discussed are suprascapular nerve entrapment, carpal tunnel syndrome, cubital tunnel syndrome, meralgia paraesthetica, thoracic outlet syndrome and anterior interosseous nerve syndrome., Carpal tunnel syndrome is a neuropathy resulting from compression of the median nerve as it passes through a narrow tunnel in the wrist on its way to the hand., More typically, carpal tunnel syndrome is the most common peripheral entrapment neuropathy encountered in industry., Carpal tunnel syndrome is the most frequently encountered peripheral nerve entrapment., Carpal tunnel syndrome, an entrapment neuropathy of the median nerve, is rarely seen in childhood., Carpal tunnel syndrome (CTS) is the most common type of peripheral nerve entrapment and is a significant cause of morbidity., Carpal tunnel syndrome (CTS) is a nerve entrapment disorder, involving the median nerve when it passes the carpal tunnel at the wrist., The carpal tunnel syndrome is the most frequent entrapment syndrome of peripheral nerves., BACKGROUND: Compression of the median nerve at the wrist, or carpal tunnel syndrome, is the most commonly recognized nerve entrapme, Carpal tunnel syndrome is the most common of the median nerve entrapments., BACKGROUND: Carpal tunnel syndrome (CTS) is by far the most common entrapment neuropathy (, Introduction: Carpal tunnel syndrome, entrapment of median nerve at the wrist, is one of the most commonly encountered peripheral neuropathies in the up, Carpal tunnel syndrome, a median nerve entrapment neuropathy, is characterized by sensorimotor deficits., Carpal tunnel syndrome (CTS) is a common form of peripheral nerve entrapment, which is observed due to compression of the median nerve at the level of the carpal tunnel in the wrist., [Carpal tunnel syndrome and other nerve entrapment syndromes].[SEP]Relations: carpal tunnel syndrome has relations: disease_disease with nerve compression syndrome, disease_disease with nerve compression syndrome, disease_disease with nerve compression syndrome, disease_disease with nerve compression syndrome, disease_disease with genetic peripheral neuropathy, disease_disease with genetic peripheral neuropathy, disease_disease with genetic peripheral neuropathy, disease_disease with genetic peripheral neuropathy, disease_phenotype_positive with Constrictive median neuropathy, disease_phenotype_positive with Constrictive median neuropathy. Definitions: fibrosis defined as following: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.. cubital tunnel syndrome defined as following: Compression of the ULNAR NERVE in the cubital tunnel, which is formed by the two heads of the flexor carpi ulnaris muscle, humeral-ulnar aponeurosis, and medial ligaments of the elbow. This condition may follow trauma or occur in association with processes which produce nerve enlargement or narrowing of the canal. Manifestations include elbow pain and PARESTHESIA radiating distally, weakness of ulnar innervated intrinsic hand muscles, and loss of sensation over the hypothenar region, fifth finger, and ulnar aspect of the ring finger. (Joynt, Clinical Neurology, 1995, Ch51, p43). Neuropathies defined as following: A disorder affecting the cranial nerves or the peripheral nervous system. It manifests with pain, tingling, numbness, and muscle weakness. It may be the result of physical injury, toxic substances, viral diseases, diabetes, renal failure, cancer, and drugs.. CTS defined as following: Entrapment of the MEDIAN NERVE in the carpal tunnel, which is formed by the flexor retinaculum and the CARPAL BONES. This syndrome may be associated with repetitive occupational trauma (CUMULATIVE TRAUMA DISORDERS); wrist injuries; AMYLOID NEUROPATHIES; rheumatoid arthritis (see ARTHRITIS, RHEUMATOID); ACROMEGALY; PREGNANCY; and other conditions. Symptoms include burning pain and paresthesias involving the ventral surface of the hand and fingers which may radiate proximally. Impairment of sensation in the distribution of the median nerve and thenar muscle atrophy may occur. (Joynt, Clinical Neurology, 1995, Ch51, p45). humans defined as following: Members of the species Homo sapiens.. thoracic outlet syndrome defined as following: A neurovascular syndrome associated with compression of the BRACHIAL PLEXUS; SUBCLAVIAN ARTERY; and SUBCLAVIAN VEIN at the superior thoracic outlet. This may result from a variety of anomalies such as a CERVICAL RIB, anomalous fascial bands, and abnormalities of the origin or insertion of the anterior or medial scalene muscles. Clinical features may include pain in the shoulder and neck region which radiates into the arm, PARESIS or PARALYSIS of brachial plexus innervated muscles, PARESTHESIA, loss of sensation, reduction of arterial pulses in the affected extremity, ISCHEMIA, and EDEMA. (Adams et al., Principles of Neurology, 6th ed, pp214-5).. chronic renal failure defined as following: The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.. tibial neuropathy defined as following: Disease of the TIBIAL NERVE (also referred to as the posterior tibial nerve). The most commonly associated condition is the TARSAL TUNNEL SYNDROME. However, LEG INJURIES; ISCHEMIA; and inflammatory conditions (e.g., COLLAGEN DISEASES) may also affect the nerve. Clinical features include PARALYSIS of plantar flexion, ankle inversion and toe flexion as well as loss of sensation over the sole of the foot. (From Joynt, Clinical Neurology, 1995, Ch51, p32). fibular defined as following: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones.. elbow defined as following: A hinge joint connecting the FOREARM to the ARM.. ulnar neuropathy defined as following: Disease involving the ULNAR NERVE from its origin in the BRACHIAL PLEXUS to its termination in the hand. Clinical manifestations may include PARESIS or PARALYSIS of wrist flexion, finger flexion, thumb adduction, finger abduction, and finger adduction. Sensation over the medial palm, fifth finger, and ulnar aspect of the ring finger may also be impaired. Common sites of injury include the AXILLA, cubital tunnel at the ELBOW, and Guyon's canal at the wrist. (From Joynt, Clinical Neurology, 1995, Ch51 pp43-5). nerve defined as following: Part of the peripheral nervous system composed of bundles of nerve fibers running to various organs and tissues of the body using chemical and electrical signals to transmit sensory and motor information from one body part to another.. fibular head defined as following: The highest portion of the fibula that articulates with the patella.. paresthesias defined as following: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation..", "label": "yes"}
{"id": "converted_512", "sentence1": "Is vemurafenib effective for hairy-cell leukemia?", "sentence2": "CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia., Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL., The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option. , Successful re-treatment of a relapsed V600E mutated HCL patient with low-dose vemurafenib., Recent identification of the recurrent V600E BRAF mutation in a majority of HCL patients has led some teams to evaluate the clinical potential of vemurafenib, a BRAF V600 specific inhibitor in a limited number of refractory HCL patients. Recently, we published the case of an HCL patient successfully treated with a low dose of vemurafenib., We present here the successful retreatment of this patient with a second line of vemurafenib. Our data suggest for the first time that vemurafenib at the dose of 240 mg once a day could be sufficient to maintain a complete hematological remission after an initial induction treatment with low-dose vemurafenib (2 × 240 mg) daily without inducing major toxicity., The discovery of the BRAF mutation has created a therapeutic target exploited by oral inhibitors like vemurafenib and dabrafenib., [Successful use of vemurafenib in a patient with resistant hairy cell leukemia]., The frequent persistence of phosphorylated ERK-positive leukemic cells in bone marrow at the end of treatment suggests bypass reactivation of MEK and ERK as a resistance mechanism.CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia. , A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia., A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia., The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option.[SEP]Relations: Vemurafenib has relations: drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Afatinib, drug_drug with Afatinib, drug_drug with Vardenafil, drug_drug with Vardenafil, drug_drug with Ethanol, drug_drug with Ethanol, drug_drug with Ribociclib, drug_drug with Ribociclib. Definitions: MEK defined as following: A dual-specific protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.. vemurafenib defined as following: An orally bioavailable, ATP-competitive, small-molecule inhibitor of BRAF(V600E) kinase with potential antineoplastic activity. Vemurafenib selectively binds to the ATP-binding site of BRAF(V600E) kinase and inhibits its activity, which may result in an inhibition of an over-activated MAPK signaling pathway downstream in BRAF(V600E) kinase-expressing tumor cells and a reduction in tumor cell proliferation. Approximately 90% of BRAF gene mutations involve a valine-to-glutamic acid mutation at residue 600 (V600E); the oncogene protein product, BRAF(V600E) kinase, exhibits a markedly elevated activity that over-activates the MAPK signaling pathway. The BRAF(V600E) gene mutation has been found to occur in approximately 60% of melanomas, and in about 8% of all solid tumors, including melanoma, colorectal, thyroid and other cancers.. toxicity defined as following: The finding of bodily harm due to the poisonous effects of something.. ERK defined as following: A superfamily of PROTEIN SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).. 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.. HCL defined as following: A neoplastic disease of the lymphoreticular cells which is considered to be a rare type of chronic leukemia; it is characterized by an insidious onset, splenomegaly, anemia, granulocytopenia, thrombocytopenia, little or no lymphadenopathy, and the presence of \"hairy\" or \"flagellated\" cells in the blood and bone marrow.. dabrafenib defined as following: An orally bioavailable inhibitor of B-raf (BRAF) protein with potential antineoplastic activity. Dabrafenib selectively binds to and inhibits the activity of B-raf, which may inhibit the proliferation of tumor cells which contain a mutated BRAF gene. B-raf belongs to the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations.. BRAF defined as following: Serine/threonine-protein kinase B-raf (766 aa, ~84 kDa) is encoded by the human BRAF gene. This protein plays a role in protein phosphorylation, mitogenesis and neuronal signal transduction.. hairy-cell leukemia defined as following: A neoplastic disease of the lymphoreticular cells which is considered to be a rare type of chronic leukemia; it is characterized by an insidious onset, splenomegaly, anemia, granulocytopenia, thrombocytopenia, little or no lymphadenopathy, and the presence of \"hairy\" or \"flagellated\" cells in the blood and bone marrow..", "label": "yes"}
{"id": "converted_3899", "sentence1": "Is erabutoxin b usually found in plants?", "sentence2": "The variants are the curaremimetic toxin alpha from Naja nigricollis and erabutoxin a or b from Laticauda semifasciata, The three-dimensional structure of erabutoxin b, a short-chain neurotoxic peptide purified from the venom of the sea snake Laticauda semifasciata, , THe characteristic feature of the crystal structure of erabutoxin b, a short neurotoxin from Laticauda semifasciata, and alpha-cobratoxin, a long neurotoxin from Naja naja siamensis, is the presence of a triple-stranded antiparallel pleated beta-sheet structure formed by the central and the third peptide loops., Here we examine the actions of six snake neurotoxins (alpha-cobratoxin from Naja naja siamensis, erabutoxin-a and b from Laticauda semifasciata; CM12 from N. haje annulifera, toxin III 4 from Notechis scutatus and a long toxin from N. haje) on nicotinic acetylcholine receptors in the cercal afferent, giant interneuron 2 synapse of the cockroach, Periplaneta americana., The method was applied to a study of erabutoxin b molecule, a neurotoxic protein from a sea snake, to analyze the microenvironments of its single tryptophan and tyrosine residues., The area of greatest similarity centered on residue position 25 of erabutoxin b, a locale that is conserved throughout the snake alpha-neurotoxins and their homologues., A systematic computer search of the three-dimensional structure of erabutoxin b (an alpha-neurotoxin from the false sea snake Laticauda semifasciata) was performed to identify the locality that most closely matched the amino acid compositions of the smaller alpha-conotoxins (from the marine snails Conus magus and Conus geographus)., Erabutoxin b is one of a family of snake venom neurotoxins, all low-molecular-weight proteins, which block neuromuscular transmission at the postsynaptic membrane., Erabutoxins a and b are neurotoxins isolated from venom of a sea snake Laticauda semifasciata (erabu-umihebi)., The three-dimensional structure of erabutoxin b, a neurotoxin in the venom of the sea snake Laticauda semifasciata, has been determined from a 2.75 A resolution electron density map., Erabutoxin c, a minor neurotoxic component of the venom of a sea snake Laticauda semifasciata, was isolated in pure form by repeated column chromatography on CM-cellulose columns., The study has established complete structural identity of the two sea-snake venom toxins, erabutoxin b and neurotoxin b, isolated from Laticauda semifasciata snakes taken in different Pacific Ocean waters., Studies on sea-snake venoms. Crystallization of erabutoxins a and b from Laticauda semifasciata venom.[SEP]Relations: postsynaptic membrane has relations: cellcomp_protein with GABRG2, cellcomp_protein with GABRG2, cellcomp_protein with GABRB3, cellcomp_protein with GABRB3, cellcomp_protein with TMUB1, cellcomp_protein with TMUB1, cellcomp_protein with GABRB1, cellcomp_protein with GABRB1, cellcomp_protein with SRGAP2, cellcomp_protein with SRGAP2. Definitions: postsynaptic membrane defined as following: A specialized area of membrane facing the presynaptic membrane on the tip of the nerve ending and separated from it by a minute cleft (the synaptic cleft). Neurotransmitters cross the synaptic cleft and transmit the signal to the postsynaptic membrane. [ISBN:0198506732]. neurotoxin defined as following: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.. erabutoxins defined as following: Toxins isolated from the venom of Laticauda semifasciata, a sea snake (Hydrophid); immunogenic, basic polypeptides of 62 amino acids, folded by four disulfide bonds, block neuromuscular end-plates irreversibly, thus causing paralysis and severe muscle damage; they are similar to Elapid neurotoxins.. sea snake defined as following: A subfamily of marine elapid snakes comprising about 50 species with flattened oar-like tails used as sculls. They are found mostly in the coastal waters of south Asia and Australia. The largest reach a length of almost 9 feet but most species are only about a third as long. They are all venomous. (Goin, Goin, and Zug, Introduction to Herpetology, 3d ed, pp331-3; Moore: Poisonous Snakes of the World, 1980, p159). nicotinic acetylcholine receptors defined as following: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.. venom defined as following: A toxin used by animals and injected into their victims by a bite or sting. variants defined as following: An alteration or difference from a norm or standard.. plants defined as following: Multicellular, eukaryotic life forms of kingdom Plantae. Plants acquired chloroplasts by direct endosymbiosis of CYANOBACTERIA. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (MERISTEMS); cellulose within cells providing rigidity; the absence of organs of locomotion; absence of nervous and sensory systems; and an alternation of haploid and diploid generations. It is a non-taxonomical term most often referring to LAND PLANTS. In broad sense it includes RHODOPHYTA and GLAUCOPHYTA along with VIRIDIPLANTAE..", "label": "no"}
{"id": "converted_1865", "sentence1": "Is adalimumab effective for hidradenitis suppurativa?", "sentence2": "If patient is not improved, then Adalimumab 160 mg at week 0, 80 mg at week 2; then 40 mg subcutaneously weekly should be administered (LOE Ib, SOR A). If improvement occurs then therapy should be maintained as long as HS lesions are present., Reduction in pain scores and improvement in depressive symptoms in patients with hidradenitis suppurativa treated with adalimumab in a phase 2, randomized, placebo-controlled trial., Adalimumab treatment for 16 weeks improved HS lesions significantly versus placebo (NCT00918255)., CONCLUSION: Patients with moderate to severe HS had a high degree of pain and depressive symptoms at baseline. Adalimumabtherapy was associated with decreased pain and depressive symptoms compared to baseline., Spotlight on adalimumab in the treatment of active moderate-to-severe hidradenitis suppurativa., Adalimumab, a recombinant, fully humanized, anti-tumor necrosis factor alpha (anti-TNF-α) monoclonal antibody, is the only officially approved treatment for the management of moderate-to-severe HS. Case reports, concerning 42 patients who received adalimumab for severe HS (with the standard dose regimen for psoriasis), reported a cumulative response rate of 58% (≥50% in 23 patients) with a relapse rate of 71% (10 out of 14 patients). The most recent and most well-powered phase III, randomized placebo-controlled trials for the evaluation of the efficacy and safety of adalimumab in treatment of moderate-to-severe HS (PIONEER studies I and II) showed that the Hidradenitis Suppurativa Clinical Response (HiSCR) rate at week 12 was significantly higher for patients randomized to adalimumab compared to placebo., In conclusion, adalimumab, to date, holds the most robust data regarding treatment efficacy in HS. , Adalimumab (Humira) for the Treatment of Hidradenitis Suppurativa., Adalimumab (Humira®) is a novel therapy approved by the US Food and Drug Administration, Health Canada, and the European Commission for the treatment of hidradenitis suppurativa (HS)., Taken together, these data conclude that treatment of HS with adalimumab is a safe and effective therapy resulting in a significant decrease in abscess and inflammatory nodule counts within the first 12 weeks of treatment., Effective long-term control of refractory hidradenitis suppurativa with adalimumab after failure of conventional therapy., Hidradenitis suppurativa managed with adalimumab., Treatment of severe recalcitrant hidradenitis suppurativa with adalimumab., Long-term successful adalimumab therapy in severe hidradenitis suppurativa., Comparing treatment outcome of infliximab and adalimumab in patients with severe hidradenitis suppurativa., HiSCR (Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo-controlled portion of a phase 2 adalimumab study, Adalimumab in treatment-resistant hidradenitis suppurativa following recurrence after extensive affected area excision: a review of biologics therapy, Adalimumab (antitumour necrosis factor-α) treatment of hidradenitis suppurativa ameliorates skin inflammation: an in situ and ex vivo study, Treatment of severe recalcitrant hidradenitis suppurativa with adalimumab, In a phase 2 trial, adalimumab, an antibody against tumor necrosis factor α, showed efficacy against hidradenitis suppurativa.PIONEER I and II were similarly designed, phase 3 multicenter trials of adalimumab for hidradenitis suppurativa, with two double-blind, placebo-controlled periods., Here we report a case of a patient with severe recalcitrant hidradenitis suppurativa successfully treated with adalimumab., Recent reports have demonstrated that adalimumab, a tumor necrosis factor (TNF) antagonist, may be effective in the treatment of patients with HS who have failed conventional therapy., Conclusion Adalimumab appears to be an effective and safe treatment for refractory HS., Effective long-term control of refractory hidradenitis suppurativa with adalimumab after failure of conventional therapy., Hidradenitis suppurativa managed with adalimumab., Treatment of severe recalcitrant hidradenitis suppurativa with adalimumab., Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa., Adalimumab treatment for hidradenitis suppurativa associated with Crohn's disease., Long-term successful adalimumab therapy in severe hidradenitis suppurativa., Conclusion Adalimumab appears to be an effective and safe treatment for refractory HS.., Comparing treatment outcome of infliximab and adalimumab in patients with severe hidradenitis suppurativa., Here we report a case of a patient with severe recalcitrant hidradenitis suppurativa successfully treated with adalimumab.., Adalimumab is suitable for the long-term treatment of hidradenitis suppurativa and presents a further conservative treatment approach.., HiSCR (Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo-controlled portion of a phase 2 adalimumab study., Spotlight on adalimumab in the treatment of active moderate-to-severe hidradenitis suppurativa.[SEP]Relations: hidradenitis suppurativa has relations: disease_disease with hidradenitis, disease_disease with hidradenitis. Adalimumab has relations: drug_drug with Amatuximab, drug_drug with Amatuximab, drug_drug with Isatuximab, drug_drug with Isatuximab, drug_drug with Margetuximab, drug_drug with Margetuximab, drug_drug with Antipyrine, drug_drug with Antipyrine. Definitions: lesions defined as following: A localized pathological or traumatic structural change, damage, deformity, or discontinuity of tissue, organ, or body part.. 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.. Adalimumab defined as following: A recombinant, human IgG1 monoclonal antibody directed against tumor necrosis factor-alpha (TNF-alpha), with immunomodulating activity. Upon administration, adalimumab binds to TNF-alpha, thereby preventing its binding to the p55 and p75 TNF cell surface receptors and inhibiting TNF-mediated immune responses. TNF-alpha, a pro-inflammatory cytokine, is upregulated in various autoimmune diseases.. TNF defined as following: A recombinant therapeutic agent which is chemically identical to or similar to one of a number of endogenous tumor necrosis factor (TNF) proteins. TNF family cytokines bind to and activate specific cell-surface receptors, thereby mediating inflammatory processes, cell proliferation, immunity, angiogenesis, and tumor cell cytotoxicity. One primary antitumor effect of TNFs involves stimulation of T cell-mediated antitumor cytotoxicity.. tumor necrosis factor defined as following: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.. 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.. Hidradenitis Suppurativa defined as following: A chronic suppurative and cicatricial disease of the apocrine glands occurring chiefly in the axillae in women and in the groin and anal regions in men. It is characterized by poral occlusion with secondary bacterial infection, evolving into abscesses which eventually rupture. As the disease becomes chronic, ulcers appear, sinus tracts enlarge, fistulas develop, and fibrosis and scarring become evident.. 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]. hidradenitis suppurativa defined as following: A chronic suppurative and cicatricial disease of the apocrine glands occurring chiefly in the axillae in women and in the groin and anal regions in men. It is characterized by poral occlusion with secondary bacterial infection, evolving into abscesses which eventually rupture. As the disease becomes chronic, ulcers appear, sinus tracts enlarge, fistulas develop, and fibrosis and scarring become evident..", "label": "yes"}
{"id": "converted_124", "sentence1": "Is DITPA a thyroid hormone analog utilized in experimental and clinical studies", "sentence2": "DITPA normalized the elevated serum T(3) and TSH when the dose reached 1 mg/kg · d and T(4) and rT(3) increased to the lower normal range., The identification of 3,5-diiodothyropropionic acid (DITPA) that binds to both α- and β-type TRs with relatively low affinity was unique in that this analog improves left ventricular function in heart failure as well as lowers cholesterol., Treatment with DITPA attenuates the acute inflammatory response and reduces myocardial infarct size., Thus DITPA administration impairs baseline cardiac parameters in mice and can be fatal during in vivo acute myocardial I/R., DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure, The results suggested that DITPA can promote a healthy vasculature independently from its thyroid-related metabolic effects. , Moreover, DITPA and T(4) were efficacious in preventing effects of hypothyroidism on cardiac function and BVD, Both T4 and DITPA had beneficial effects on chamber remodeling, which was most likely due to beneficial changes in cell shape and improved vascular supply., The thyroid analog DITPA enhances endothelial nitric oxide and beta-adrenergic-mediated vasorelaxation by increasing nitric oxide in the vasculature.[SEP]Relations: 3,5-diiodothyropropionic acid has relations: drug_drug with Ethionamide, drug_drug with Ethionamide, drug_drug with Motesanib, drug_drug with Motesanib, drug_drug with Ritonavir, drug_drug with Ritonavir, drug_drug with Escitalopram, drug_drug with Escitalopram, drug_drug with Flumatinib, drug_drug with Flumatinib. Definitions: nitric oxide defined as following: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.. vasculature defined as following: Organ region cluster which consists of regions of arterial, venous and lymphatic trees and the capillary beds that connect them. Examples: Vasculature of head, vasculature of brain.. heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. 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.. TRs defined as following: Catalysis of the reaction: ATP + L-threonine + tRNA(Thr) = AMP + diphosphate + L-threonyl-tRNA(Thr). [EC:6.1.1.3]. thyroid hormone defined as following: Natural hormones secreted by the THYROID GLAND, such as THYROXINE, and their synthetic analogs..", "label": "yes"}
{"id": "converted_4131", "sentence1": "Can Panitumumab cause trichomegaly?", "sentence2": "Xerosis was present in two cases, and paronychia, pyogenic granuloma, trichomegaly, and madarosis were observed in one patient each. , Eyelash trichomegaly is an uncommon drug-associated sequelae experienced during treatment with epidermal growth factor receptor (EGFR) inhibitors. Elongation of the eyelashes induced by these agents has predominantly been observed in oncology patients with either colorectal or lung cancer. It is most frequently associated with cetuximab and erlotinib; however, it has also been described in individuals treated with gefitinib or panitumumab. , Trichomegaly of the eyelashes during therapy with epidermal growth factor receptor inhibitors: report of 3 cases., Trichomegaly of the eyelashes is a rare adverse effect of EGFR inhibitor therapy and is characterized by a paradoxical overgrowth of eyelashes.[SEP]Relations: Panitumumab has relations: drug_drug with Tregalizumab, drug_drug with Tregalizumab, drug_drug with Pertuzumab, drug_drug with Pertuzumab, drug_drug with Sonepcizumab, drug_drug with Sonepcizumab, drug_drug with Concizumab, drug_drug with Concizumab, drug_drug with Eculizumab, drug_drug with Eculizumab. Definitions: gefitinib defined as following: A selective tyrosine kinase inhibitor for the EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) that is used for the treatment of locally advanced or metastatic NON-SMALL CELL LUNG CANCER.. erlotinib defined as following: A quinazoline derivative with antineoplastic properties. Competing with adenosine triphosphate, erlotinib reversibly binds to the intracellular catalytic domain of epidermal growth factor receptor (EGFR) tyrosine kinase, thereby reversibly inhibiting EGFR phosphorylation and blocking the signal transduction events and tumorigenic effects associated with EGFR activation.. eyelashes defined as following: The hairs which project from the edges of the EYELIDS.. panitumumab defined as following: A human IgG2kappa monoclonal antibody specific for the epidermal growth factor receptor (EGFR). Monoclonal antibody E7.6.3 binds to the EGFR, blocking the binding of epidermal growth factor and transforming growth factor alpha to EGFR-expressing cancer cells and ultimately inhibiting EGFR-dependent cell activation and proliferation. (NCI). 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.. epidermal growth factor receptor inhibitors defined as following: Any tyrosine kinase inhibitor that targets the activity of the epidermal growth factor receptor (EGFR) tyrosine kinase. Inhibition of epidermal growth factor receptor tyrosine kinase may inhibit the growth of epidermal-lineage tumor cells, especially those that overexpress epidermal growth factor receptor..", "label": "yes"}
{"id": "converted_1899", "sentence1": "Have the promoter regions of the genes implicated in Rett Syndrome been characterized with CAGE?", "sentence2": "CAGE-defined promoter regions of the genes implicated in Rett Syndrome., Mutations in three functionally diverse genes cause Rett Syndrome. Although the functions of Forkhead box G1 (FOXG1), Methyl CpG binding protein 2 (MECP2) and Cyclin-dependent kinase-like 5 (CDKL5) have been studied individually, not much is known about their relation to each other with respect to expression levels and regulatory regions. Here we analyzed data from hundreds of mouse and human samples included in the FANTOM5 project, to identify transcript initiation sites, expression levels, expression correlations and regulatory regions of the three genes.RESULTS: Our investigations reveal the predominantly used transcription start sites (TSSs) for each gene including novel transcription start sites for FOXG1. We show that FOXG1 expression is poorly correlated with the expression of MECP2 and CDKL5. We identify promoter shapes for each TSS, the predicted location of enhancers for each gene and the common transcription factors likely to regulate the three genes. Our data imply Polycomb Repressive Complex 2 (PRC2) mediated silencing of Foxg1 in cerebellum.CONCLUSIONS: Our analyses provide a comprehensive picture of the regulatory regions of the three genes involved in Rett Syndrome., CAGE-defined promoter regions of the genes implicated in Rett Syndrome, CAGE-defined promoter regions of the genes implicated in Rett Syndrome.[SEP]Relations: Rett syndrome has relations: disease_protein with NTNG1, disease_protein with NTNG1, disease_phenotype_positive with Increased serum leptin, disease_phenotype_positive with Increased serum leptin, disease_disease with X-linked complex neurodevelopmental disorder, disease_disease with X-linked complex neurodevelopmental disorder, disease_protein with MECP2, disease_protein with MECP2, disease_phenotype_positive with Increased serum pyruvate, disease_phenotype_positive with Increased serum pyruvate. Definitions: gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. Polycomb Repressive Complex 2 defined as following: A multisubunit polycomb protein complex that catalyzes the METHYLATION of chromosomal HISTONE H3. It works in conjunction with POLYCOMB REPRESSIVE COMPLEX 1 to effect EPIGENETIC REPRESSION.. Forkhead box G1 defined as following: This gene is involved in transcriptional repression and may play a role in the development of the brain and telencephalon.. Rett Syndrome defined as following: This gene plays a role in both the recognition of DNA methylation and the regulation of transcription.. CDKL5 defined as following: This gene plays a role in protein metabolism.. regulatory regions defined as following: Nucleic acid sequences involved in regulating the expression of genes.. MECP2 defined as following: Methyl-CpG-binding protein 2 (486 aa, ~52 kDa) is encoded by the human MECP2 gene. This protein plays a role in the repression of transcription through binding methylated DNA.. Methyl CpG binding protein 2 defined as following: A DNA-binding protein that interacts with methylated CPG ISLANDS. It plays a role in repressing GENETIC TRANSCRIPTION and is frequently mutated in RETT SYNDROME.. human defined as following: Members of the species Homo sapiens.. transcription start sites defined as following: The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.. cerebellum defined as following: The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the \"little brain\" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. promoter regions defined as following: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"}
{"id": "converted_150", "sentence1": "Is PTEN involved in follicular thyroid carcinoma?", "sentence2": "Two of the 259 patients (0.8%), with both follicular thyroid carcinoma and macrocephaly, were found to carry a germline mutation in the PTEN gene. The PTEN mutation frequency in unselected cases of follicular thyroid carcinoma was 4.8%, The frequency of germline pathogenic PTEN mutations in an unselected series of patients with DTC is relatively low, but it is enriched by considering follicular histology and macrocephaly, Similarly, there is increasing evidence demonstrating that mutations leading to activation of the phosphatidylinositol 3- kinase (PI3K)/AKT effectors -PTEN and PI3KCa- are essential for the pathogenesis of follicular thyroid carcinoma (FTC), A single male with follicular thyroid carcinoma from one of these 64 (2%) CS-like families harboured a germline point mutation, c.209T-->C, Similarly, there is increasing evidence demonstrating that mutations leading to activation of the phosphatidylinositol 3- kinase (PI3K)/AKT effectors -PTEN and PI3KCa- are essential for the pathogenesis of follicular thyroid carcinoma (FTC)., The transcriptional silencing of PTEN was significantly associated with the anaplastic subtype, suggesting that PTEN is involved in the carcinogenesis of highly malignant or late-stage thyroid cancers, whereas this particular mechanism appears to be of minor importance in differentiated follicular thyroid tumors., These results show a high frequency of PTEN promoter hypermethylation, especially in follicular tumors, suggesting its possible role in thyroid tumorigenesis, Our findings suggest that the PTEN tumor suppressor gene is occasionally inactivated in sporadic follicular thyroid tumors, Germline mutations in the tumor suppressor gene PTEN, which encodes a dual-specificity phosphatase, have been found in up to 80% of patients with Cowden syndrome suggesting a role of PTEN in the pathogenesis of follicular thyroid tumors, The most common neoplasms in Cowden disease patients arise in the breast, skin, and thyroid (follicular subtype), The transcriptional silencing of PTEN was significantly associated with the anaplastic subtype, suggesting that PTEN is involved in the carcinogenesis of highly malignant or late-stage thyroid cancers, whereas this particular mechanism appears to be of minor importance in differentiated follicular thyroid tumors[SEP]Relations: PTEN has relations: disease_protein with thyroid gland carcinoma, disease_protein with thyroid gland carcinoma, disease_protein with thyroid cancer, disease_protein with thyroid cancer, anatomy_protein_present with thyroid gland, anatomy_protein_present with thyroid gland, disease_protein with carcinoma, disease_protein with carcinoma, disease_protein with prostate carcinoma, disease_protein with prostate carcinoma. Definitions: dual-specificity phosphatase defined as following: A sub-class of protein tyrosine phosphatases that contain an additional phosphatase activity which cleaves phosphate ester bonds on SERINE or THREONINE residues that are located on the same protein.. PTEN defined as following: Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (403 aa, ~47 kDa) is encoded by the human PTEN gene. This protein plays a role in signaling and as both a dual-specificity phosphoprotein phosphatase and a lipid phosphatase.. FTC defined as following: A synthetic fluoro derivative of thiacytidine with potent antiviral activity. Emtricitabine is phosphorylated to form emtricitabine 5'-triphosphate within the cell. This metabolite inhibits the activity of human immunodeficiency virus (HIV) reverse transcriptase both by competing with the natural substrate deoxycytidine 5'-triphosphate and by incorporation into viral DNA causing a termination of DNA chain elongation (due to the lack of the essential 3'-OH group).. 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.. follicular thyroid carcinoma defined as following: An adenocarcinoma of the thyroid gland, in which the cells are arranged in the form of follicles. (From Dorland, 27th ed). 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.. thyroid cancers defined as following: A primary or metastatic malignant neoplasm affecting the thyroid gland.. DTC defined as following: A chelating agent that has been used to mobilize toxic metals from the tissues of humans and experimental animals. It is the main metabolite of DISULFIRAM.. PTEN gene defined as following: This gene plays a role in signal transduction and apoptosis. It is also involved in the regulation of cell cycle progression.. macrocephaly defined as following: A congenital abnormality in which the occipitofrontal circumference is greater than two standard deviations above the mean for a given age. It is associated with HYDROCEPHALUS; SUBDURAL EFFUSION; ARACHNOID CYSTS; or is part of a genetic condition (e.g., ALEXANDER DISEASE; SOTOS SYNDROME).. Cowden disease defined as following: A hereditary disease characterized by multiple ectodermal, mesodermal, and endodermal nevoid and neoplastic anomalies. Facial trichilemmomas and papillomatous papules of the oral mucosa are the most characteristic lesions. Individuals with this syndrome have a high risk of BREAST CANCER; THYROID CANCER; and ENDOMETRIAL CANCER. This syndrome is associated with mutations in the gene for PTEN PHOSPHATASE.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA..", "label": "yes"}
{"id": "converted_1878", "sentence1": "Is there alternative polyadenylation during zebrafish development?", "sentence2": "Extensive alternative polyadenylation during zebrafish development., At 2 h post-fertilization, thousands of unique poly(A) sites appear at locations lacking a typical polyadenylation signal, which suggests a wave of widespread cytoplasmic polyadenylation of mRNA degradation intermediates. Our insights into the identities, formation, and evolution of zebrafish 3' UTRs provide a resource for studying gene regulation during vertebrate development., Extensive alternative polyadenylation during zebrafish development.[SEP]Relations: vertebra has relations: anatomy_anatomy with non-transverse process-bearing vertebra, anatomy_anatomy with non-transverse process-bearing vertebra, anatomy_anatomy with transverse process-bearing vertebra, anatomy_anatomy with transverse process-bearing vertebra, anatomy_anatomy with predorsal vertebra, anatomy_anatomy with predorsal vertebra, anatomy_anatomy with vertebral element, anatomy_anatomy with vertebral element, anatomy_anatomy with vertebral bone 2, anatomy_anatomy with vertebral bone 2. Definitions: zebrafish defined as following: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research.. vertebrate defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes..", "label": "yes"}
{"id": "converted_3960", "sentence1": "Is avelumab effective for urothelial carcinoma?", "sentence2": "ince then, additional checkpoint inhibitors, including avelumab, durvalumab, and nivolumab, have gained approval. , Avelumab, an anti-programmed death-ligand 1 monoclonal antibody approved for the treatment of metastatic Merkel cell carcinoma and platinum-treated urothelial carcinoma, was initially approved with a 10 mg/kg weight-based dose. , Five new PD-1/PD-L1 checkpoint inhibitors have been approved for the treatment of metastatic urothelial carcinoma (UC): pembrolizumab, atezolizumab, durvalumab, nivolumab, and avelumab. , We reviewed the literature for prospective studies evaluating PD-1/PD-L1 inhibitors in refractory urothelial carcinoma patients, which formed the basis for US Food and Drug Administration approval of 5 different antagonistic antibodies targeting PD-1 or PD-L1 (atezolizumab, durvalumab, avelumab, nivolumab, and pembrolizumab)., Nowadays, five immune checkpoint inhibitors blocking PD-1 (pembrolizumab, nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved by the United States Food and Drug Administration (US FDA) for the first- or second-line use in urothelial carcinoma, based on durable response and manageable safety profiles observed in relevant clinical trials. , RETATION: Avelumab showed antitumour activity in the treatment of patients with platinum-refractory metastatic urothelial carcinoma; a manageable safety profile was reported in all avelumab-treated patients. These, data provide the rationale for therapeutic use of avelumab in metastatic urothelial carcinoma and it has received accelerated US FDA approval in this setting on this basis.FUNDIN, BACKGROUND: Anti-programmed cell death ligand 1 (PD-L1)/programmed cell death 1 antibodies have shown clinical activity in platinum-treated metastatic urothelial carcinoma, resulting in regulatory approval of several agents, including avelumab (anti-PD-L1)., Avelumab as second-line therapy for metastatic, platinum-treated urothelial carcinoma in the phase Ib JAVELIN Solid Tumor study: 2-year updated efficacy and safety analysis., BACKGROUND: Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma., SIONS: Maintenance avelumab plus best supportive care significantly prolonged overall survival, as compared with best supportive care alone, among patients with urothelial cancer who had disease that had not progressed with first-line chemotherapy. (Fund, By the emergence of modern immunotherapies with active agents like PD-1 (nivolumab, pembrolizumab) and PD-L1 immune checkpoint blockers (atezolizumab, avelumab, durvalumab), new therapeutic options have become available for the treatment of patients with locally advanced and metastatic urothelial carcinoma., Avelumab, an anti-programmed death-ligand 1 monoclonal antibody approved for the treatment of metastatic Merkel cell carcinoma and platinum-treated urothelial carcinoma, was initially approved with a 10 mg/kg weight-based dose., By the emergence of modern immunotherapies with active agents like PD-1 (nivolumab, pembrolizumab) and PD-L1 immune checkpoint blockers (atezolizumab, avelumab, durvalumab), new therapeutic options have become available for the treatment of patients with locally advanced and metastatic urothelial carcinoma. Accor, ACQUISITION: Five antibodies including pembrolizumab (PD-L1 antibody), atezolizumab (PD-1 antibody), nivolumab (PD-1 antibody), avelumab and durvalumab (PD-L1 antibodies) have been approved in the treatment of advanced urothelial carcinoma in first- and second-line treatment setting., INTERPRETATION: Avelumab showed antitumour activity in the treatment of patients with platinum-refractory metastatic urothelial carcinoma; a manageable safety profile was reported in all avelumab-treated patients., Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC., Avelumab: A Novel Anti-PD-L1 Agent in the Treatment of Merkel Cell Carcinoma and Urothelial Cell Carcinoma., In early 2017, avelumab (BAVENCIO®), a PD-L1-blocking monoclonal antibody agent, was approved for the treatment of metastatic MCC and UC., Expert opinion: Avelumab has shown clinical efficacy for metastatic and advanced UC in phase I studies after the failure of platinum-based therapy with a well-tolerated safety profile., Avelumab has been approved by the U.S. FDA for the treatment of metastatic Merkel cell carcinoma and metastatic urothelial carcinoma that has progressed during or following treatment with a platinum-based regimen.[SEP]Relations: Nivolumab has relations: drug_drug with Avelumab, drug_drug with Avelumab, drug_drug with Urelumab, drug_drug with Urelumab, drug_drug with Cemiplimab, drug_drug with Cemiplimab. urothelial carcinoma has relations: disease_disease with urothelial neoplasm, disease_disease with urothelial neoplasm, disease_protein with HRAS, disease_protein with HRAS. Definitions: PD-1 defined as following: Human PDCD1 wild-type allele is located in the vicinity of 2q37.3 and is approximately 9 kb in length. This allele, which encodes programmed cell death protein 1, plays a role in the modulation of both apoptosis and cellular immunity. Mutation of the gene is associated with systemic lupus erythematosus type 2.. PD-L1 defined as following: Human CD274 wild-type allele is located in the vicinity of 9p24 and is approximately 20 kb in length. This allele, which encodes programmed cell death 1 ligand 1 protein, plays a role in the regulation of T cell stimulation and proliferation.. Merkel cell carcinoma defined as following: A carcinoma arising from MERKEL CELLS located in the basal layer of the epidermis and occurring most commonly as a primary neuroendocrine carcinoma of the skin. Merkel cells are tactile cells of neuroectodermal origin and histologically show neurosecretory granules. The skin of the head and neck are a common site of Merkel cell carcinoma, occurring generally in elderly patients. (Holland et al., Cancer Medicine, 3d ed, p1245). UC defined as following: Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.. nivolumab defined as following: A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Upon administration, nivolumab binds to and blocks the activation of PD-1, an immunoglobulin superfamily (IgSF) transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). This results in the activation of T-cells and cell-mediated immune responses against tumor cells. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity.. 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]. urothelial carcinoma defined as following: A malignant neoplasm derived from TRANSITIONAL EPITHELIAL CELLS, occurring chiefly in the URINARY BLADDER; URETERS; or RENAL PELVIS.. 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.. metastatic urothelial carcinoma defined as following: A carcinoma that arises from the urothelium and has spread from its original site of growth to another anatomic site..", "label": "yes"}
{"id": "converted_51", "sentence1": "Is peripheral neuroepithelioma related to Ewing sarcoma?", "sentence2": "The term \"small round-cell tumor\" describes a group of highly aggressive malignant tumors composed of relatively small and monotonous undifferentiated cells with high nuclear to cytoplasmic ratios. This group includes Ewing's sarcoma (ES), peripheral neuroepithelioma (aka, primitive neuroectodermal tumor or extraskeletal ES), peripheral neuroblastoma (\"classic-type\"), rhabdomyosarcoma, desmoplastic small round-cell tumor, lymphoma, leukemia, small-cell osteosarcoma, small-cell carcinoma (either undifferentiated or neuroendocrine), olfactory neuroblastoma, cutaneous neuroendocrine carcinoma (aka, Merkel-cell carcinoma), small-cell melanoma, and mesenchymal chondrosarcoma. Their clinical presentations often overlap, thus making a definitive diagnosis problematic in some cases, AIMS: To retrospectively study the DNA content in a series of childhood Ewing Family Tumors (EFT), and to investigate its prognostic value. METHODS: The study was performed on a series of 27 EFTs (osseous Ewing's sarcoma, 18 cases; extraosseous Ewing's sarcoma, 2; peripheral neuroepithelioma, 4; Askin Rosai tumors, 3, To improve the prognosis of patients with poor-risk peripheral primitive neuroectodermal tumors (pPNETs; including peripheral neuroepithelioma and Ewing's sarcoma), Large group of small-round-cell tumours of soft tissues and bone represents a complex diagnostic problem for the pathologists. Neuronal nature of many tumours from this group is proven by means of new methods--immunophenotypic analysis, tissue culture, cytogenetics. Peripheral neuroepithelioma, Ewing tumour, primitive neuroectodermal tumour (PNET), Askin tumour belong to these neoplasms, Comparison of Ewing's sarcoma of bone and peripheral neuroepithelioma. An immunocytochemical and ultrastructural analysis of two primitive neuroectodermal neoplasms, Ewing's sarcoma of bone (ESB) and peripheral neuroepithelioma (PN) are frequently considered to be different tumors. Some researchers have suggested that PN is morphologically a neuroectodermal Ewing's sarcoma. We sought to determine the extent of neuroectodermal features in conventional ESB on direct patient material (25 cases) and to compare these tumors with a similar group of readily diagnosed PNs (10 cases), Neuroectodermal antigens (neuron-specific enolase, Leu-7 [HNK-1], neurofilament 200 kd, and S100) were found in nine of 10 cases of PN and in 17 of 25 cases of ESB, These data support the concept that ESB and PN are both peripheral primitive neuroectodermal neoplasms, differing only in extent of neuroectodermal phenotype and morphological differentiation, Besides these antigenic features, Ewing sarcoma cells are characterized by a specific t(11;22)(q24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor, suggesting a possible evolutionary related origin., Ewings sarcoma (ES) and peripheral neuroepithelioma (PN) are closely related tumors, and it can be difficult to distinguish them from other small-round-cell tumors (SRCTs)., The presence of this translocation in Ewing sarcoma and peripheral primitive neuroectodermal tumor has been taken as evidence that these two tumors are related., Besides these antigenic features, Ewing sarcoma cells are characterized by a specific t(11;22)(q24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor, suggesting a possible evolutionary related origin., Indistinguishable patterns of protooncogene expression in two distinct but closely related tumors: Ewing's sarcoma and neuroepithelioma., Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are related tumors, possibly of neural crest origin, which are cytogenetically characterized by the specific translocation t(11;22)(q24;q12)., Ewing's sarcoma/peripheral primitive neuroectodermal tumors (ES/pPNET) are a group of small round cell sarcomas that show varying degrees of neuroectodermal differentiation characterized by translocation involving the EWS gene, Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are closely related tumors, and it can be difficult to distinguish them from other small-round-cell tumors (SRCTs), Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are related tumors, possibly of neural crest origin, which are cytogenetically characterized by the specific translocation t(11;22)(q24;q12), This genetical similarity further supports a nosological concept according to which Askin's tumour, Ewing's sarcoma and peripheral neuroepithelioma represent phenotypic variations of the same tumour, namely the peripheral primitive neuroectodermal tumour., Besides these antigenic features, Ewing sarcoma cells are characterized by a specific t(11;22)(q24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor, suggesting a possible evolutionary related origin[SEP]Relations: Ewing sarcoma/peripheral primitive neuroectodermal tumor has relations: disease_disease with Ewing sarcoma, disease_disease with Ewing sarcoma, disease_disease with extraskeletal Ewing sarcoma/peripheral primitive neuroectodermal tumor, disease_disease with extraskeletal Ewing sarcoma/peripheral primitive neuroectodermal tumor, disease_disease with peripheral primitive neuroectodermal tumor, disease_disease with peripheral primitive neuroectodermal tumor, disease_disease with Ewing sarcoma/peripheral primitive neuroectodermal tumor of bone, disease_disease with Ewing sarcoma/peripheral primitive neuroectodermal tumor of bone. Ewing sarcoma has relations: disease_disease with Ewing sarcoma/peripheral primitive neuroectodermal tumor, disease_disease with Ewing sarcoma/peripheral primitive neuroectodermal tumor. Definitions: Askin tumour defined as following: A primitive neuroectodermal tumor (small round blue cell tumor) of the thorax which can involve the periosteum, thoracic wall and/or pleura though it spares the lung parenchyma.. neuroectodermal tumour defined as following: Malignant neoplasms arising in the neuroectoderm, the portion of the ectoderm of the early embryo that gives rise to the central and peripheral nervous systems, including some glial cells.. peripheral neuroepithelioma defined as following: A small round cell tumor with neural differentiation arising from the bone. It may be associated with pain.. ESB defined as following: A family of enzymes that hydrolyze carboxylic esters.. 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).. lymphoma defined as following: A general term for various neoplastic diseases of the lymphoid tissue.. tumour defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. neurofilament defined as following: Neurofilament medium polypeptide (916 aa, ~102 kDa) is encoded by the human NEFM gene. This protein is involved in the regulation of neuronal process structure.. Ewing sarcoma defined as following: A small round cell tumor that lacks morphologic, immunohistochemical, and electron microscopic evidence of neuroectodermal differentiation. It represents one of the two ends of the spectrum called Ewing sarcoma/peripheral neuroectodermal tumor. It affects mostly males under age 20, and it can occur in soft tissue or bone. Pain and the presence of a mass are the most common clinical symptoms.. neuroepithelioma defined as following: A group of malignant tumors of the nervous system that feature primitive cells with elements of neuronal and/or glial differentiation. Use of this term is limited by some authors to central nervous system tumors and others include neoplasms of similar origin which arise extracranially (i.e., NEUROECTODERMAL TUMORS, PRIMITIVE, PERIPHERAL). This term is also occasionally used as a synonym for MEDULLOBLASTOMA. In general, these tumors arise in the first decade of life and tend to be highly malignant. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2059). desmoplastic small round-cell tumor defined as following: A rare, aggressive soft tissue sarcoma that primarily affects adolescents and young adults. It is most commonly found in the abdomen.. soft tissues defined as following: A general term comprising tissue that is not hardened or calcified; including muscle, fat, blood vessels, nerves, tendons, ligaments and fascia.. peripheral neuroblastoma defined as following: A neuroblastoma arising from the peripheral nervous system.. rhabdomyosarcoma defined as following: A malignant mesenchymal tumor with skeletal muscle differentiation affecting the anus.. Ewing's sarcoma defined as following: A small round cell bone tumor that lacks morphologic, immunohistochemical, and electron microscopic evidence of neuroectodermal differentiation. It represents one of the two ends of the spectrum called Ewing sarcoma/peripheral neuroectodermal tumor. It often affects the diaphysis or metaphyseal-diaphyseal portion of long bones. Clinical findings include pain and a mass in the involved area. Fever, anemia, leukocytosis, and an increased sedimentation rate are often seen. X-ray examination reveals osteolytic lesions. The prognosis depends on the stage, anatomic location, and size of the tumor.. mesenchymal chondrosarcoma defined as following: A rare aggressive variant of chondrosarcoma, characterized by a biphasic histologic pattern of small compact cells intermixed with islands of cartilaginous matrix. Mesenchymal chondrosarcomas have a predilection for flat bones; long tubular bones are rarely affected. They tend to occur in the younger age group and are highly metastatic. (DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1456). leukemia defined as following: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006). HNK-1 defined as following: A carbohydrate molecule that contains a sulfoglucuronyl residue and found predominantly on the surface of natural killer cells. It is involved in the modulation of cell-cell and cell-matrix interactions.. PNET defined as following: A group of highly cellular primitive round cell neoplasms which occur extracranially in soft tissue and bone and are derived from embryonal neural crest cells. These tumors occur primarily in children and adolescents and share a number of characteristics with EWING SARCOMA.. PNs defined as following: A minimally invasive form of electroanalgesia often used in neuropathic pain. For best effect, the stimulation is applied proximally to the site of the nerve lesion. (from White, Li, and Chiu). PN defined as following: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors.. neuroendocrine defined as following: A system of NEURONS that has the specialized function to produce and secrete HORMONES, and that constitutes, in whole or in part, an ENDOCRINE SYSTEM or organ.. peripheral defined as following: On or near an edge or constituting an outer boundary; the outer area.. cutaneous neuroendocrine carcinoma defined as following: A carcinoma arising from MERKEL CELLS located in the basal layer of the epidermis and occurring most commonly as a primary neuroendocrine carcinoma of the skin. Merkel cells are tactile cells of neuroectodermal origin and histologically show neurosecretory granules. The skin of the head and neck are a common site of Merkel cell carcinoma, occurring generally in elderly patients. (Holland et al., Cancer Medicine, 3d ed, p1245). S100 defined as following: Human S100A1 wild-type allele is located in the vicinity of 1q21 and is approximately 4 kb in length. This allele, which encodes protein S100-A1, is involved in the binding of zinc and calcium.. EWS gene defined as following: This gene may play a role in post-transcriptional regulation; however the function remains to be elucidated. Mutations in the gene result in Ewing sarcoma and other tumors..", "label": "yes"}
{"id": "converted_4434", "sentence1": "Is Satb1 a transcription factor?", "sentence2": "Special AT-rich sequence binding protein-1 (SATB1) is localized to the nucleus and remodels chromatin structure in T cells, chromatin organizers SATB2 and SATB1 , transcription factor complexes. These MYB complexes assemble aberrantly with LYL1, E2A, C/EBP family members, LMO2, and SATB1. , Staining for the transcription factors Foxp2, Satb1 and Satb2 labeled most ganglion cells in the avian ganglion cell layer.[SEP]Relations: Tat protein binding has relations: molfunc_protein with DNAJA1, molfunc_protein with DNAJA1, molfunc_protein with DNAJA1, molfunc_protein with DNAJA1, molfunc_protein with GABARAPL1, molfunc_protein with GABARAPL1, molfunc_protein with GABARAPL1, molfunc_protein with GABARAPL1. Protein S human has relations: drug_drug with Factor XIII (human), drug_drug with Factor XIII (human). Definitions: Satb1 defined as following: DNA-Binding Protein SATB1 (763 aa, ~86 kDa) is encoded by the human SATB1 gene. This protein binds DNA and may be involved in the regulation of transcription.. ganglion cells defined as following: A type of interneuron that conveys information to the brain.. LMO2 defined as following: Human LMO2 wild-type allele is located in the vicinity of 11p13 and is approximately 34 kb in length. This allele, which encodes rhombotin-2 protein, is involved in red blood cell development through the modulation of transcription by RNA polymerase II.. nucleus defined as following: The region of an atom that contains the protons and neutrons.. 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.. LYL1 defined as following: Protein lyl-1 (280 aa, ~30 kDa) is encoded by the human LYL1 gene. This protein is involved in blood vessel maturation and transcriptional regulation.. Satb2 defined as following: DNA-binding protein SATB2 (733 aa, ~83 kDa) is encoded by the human SATB2 gene. This protein is involved in both DNA binding and transcriptional regulation.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. Foxp2 defined as following: This gene is involved in brain development.. E2A defined as following: Human TCF3 wild-type allele is located in the vicinity of 19p13.3 and is approximately 43 kb in length. This allele, which encodes transcription factor E2-alpha protein, plays a role in the mediation of embryological cell fate. Chromosomal aberrations involving the gene are associated with forms of pre-B-cell acute lymphoblastic leukemia.. transcription factor defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process..", "label": "yes"}
{"id": "converted_3068", "sentence1": "Has the protein SIRT2 been associated to cervical cancer?", "sentence2": " A progressive increase in the expression of both SIRT2 and SIRT7 was noted during cancer progression in the following order: normal < preneoplasia < cancer., We demonstrate that treatment of cervical cancer cells with a RhoGDIα-derived K52-trifluoroacetylated, substrate-derived peptidic sirtuin inhibitor severely impairs cell proliferation. [SEP]Relations: PPP1R1A has relations: disease_protein with liver cancer, disease_protein with liver cancer, protein_protein with ACTA2, protein_protein with ACTA2, protein_protein with ZPBP2, protein_protein with ZPBP2, anatomy_protein_present with spinal cord, anatomy_protein_present with spinal cord. NAD-dependent protein deacetylase activity has relations: molfunc_protein with SIRT2, molfunc_protein with SIRT2. Definitions: SIRT7 defined as following: NAD-dependent protein deacetylase sirtuin-7 (400 aa, ~45 kDa) is encoded by the human SIRT7 gene. This protein plays a role in protein deacetylation.. SIRT2 defined as following: A sirtuin family member found primarily in the CYTOPLASM. It is a multifunctional enzyme that contains a NAD-dependent deacetylase activity that is specific for HISTONES and a mono-ADP-ribosyltransferase activity.. cervical cancer defined as following: A primary or metastatic malignant neoplasm involving the cervix..", "label": "yes"}
{"id": "converted_2140", "sentence1": "Is it feasible to obtain DNA read lengths that exceed 30 Kb?", "sentence2": "Single-molecule, real-time sequencing (SMRT) developed by Pacific BioSciences produces longer reads than secondary generation sequencing technologies such as Illumina. The long read length enables PacBio sequencing to close gaps in genome assembly, reveal structural variations, and identify gene isoforms with higher accuracy in transcriptomic sequencing., Third-generation sequencing, with read lengths>10 kb, will improve the assembly of complex genomes, but these techniques require high-molecular-weight genomic DNA (gDNA), and gDNA extraction protocols used for obtaining smaller fragments for short-read sequencing are not suitable for this purpose., The emergence and development of so called third generation sequencing platforms such as PacBio has permitted exceptionally long reads (over 20 kb) to be generated.[SEP]Definitions: genomic DNA defined as following: The DNA that is part of the normal chromosomal complement of an organism.. fragments defined as following: A physical quality in which the entity or structure is broken into pieces.. SMRT defined as following: Human NCOR2 wild-type allele is located in the vicinity of 12q24 and is approximately 194 kb in length. This allele, which encodes nuclear receptor corepressor 2 protein, plays a role in both chromatin structural alteration and transcriptional regulation.. genome assembly defined as following: An annotated assembly of genome sequences created by the assimilation of data pieces from numerous sources.. 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": "no"}
{"id": "converted_2871", "sentence1": "Are de novo mutations in regulatory elements responsible for neurodevelopmental disorders?", "sentence2": "The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism., We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism., Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders., We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. , Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. , De novo mutations in regulatory elements in neurodevelopmental disorders.We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. [SEP]Relations: complex neurodevelopmental disorder has relations: disease_disease with developmental and epileptic encephalopathy, disease_disease with developmental and epileptic encephalopathy, disease_disease with nervous system disorder, disease_disease with nervous system disorder, disease_disease with pervasive developmental disorder, disease_disease with pervasive developmental disorder, disease_disease with Prader-Willi syndrome, disease_disease with Prader-Willi syndrome. developmental disability has relations: disease_protein with NTRK2, disease_protein with NTRK2. Definitions: developmental disorders defined as following: Disorders in which there is a delay in development based on that expected for a given age level or stage of development. These impairments or disabilities originate before age 18, may be expected to continue indefinitely, and constitute a substantial impairment. Biological and nonbiological factors are involved in these disorders. (From American Psychiatric Glossary, 6th ed). fetal defined as following: Care provided the pregnant woman in order to prevent complications, and decrease the incidence of maternal and prenatal mortality.. 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.. pathogenic defined as following: A genetic variant that is known to directly contribute to the development of disease.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. neurodevelopmental disorders defined as following: A childhood disorder that has a neurological basis and manifests as a developmental disability..", "label": "yes"}
{"id": "converted_159", "sentence1": "Is glycyl-tRNA synthetase gene involved in the development of Charcot-Marie-Tooth disease?", "sentence2": "Charcot-Marie-Tooth disease type 2D (CMT2D) is an autosomal-dominant axonal peripheral neuropathy characterized by impaired motor and sensory function in the distal extremities. Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D, Dominant mutations in GARS cause rare forms of Charcot-Marie-Tooth disease and distal spinal muscular atrophy, Using exome sequencing she was found to harbor compound heterozygous mutations within the glycyl-tRNA synthetase (GARS) gene, mutations of human GlyRS (hGlyRS) were also found to be associated with Charcot-Marie-Tooth disease, Dominant mutations in GARS, encoding the essential enzyme glycyl-tRNA synthetase (GlyRS), result in a form of Charcot-Marie-Tooth disease, type 2D (CMT2D), predominantly characterized by lower motor nerve degeneration, A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement, Here we describe a 45-year-old woman with a long course of motor-dominant neuropathy. Distal weakness appeared in childhood and became worse with age. After a diagnosis of CMT type 2, the symptoms progressed, and in her fourth decade, facial and respiratory muscle weakness appeared, ultimately requiring non-invasive mechanical ventilation. There was no family history of CMT. Comprehensive analysis of known CMT-related genes revealed a novel heterozygous c.815T>A, p.L218Q mutation in glycyl-tRNA synthetase (GARS), a causative gene for both CMT type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V), Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS)., Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase., Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V., [A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement]., Glycyl-tRNA synthetase (GARS), which encodes the enzyme responsible for charging tRNA(Gly) with glycine in both the cytoplasm and mitochondria, is implicated to Charcot-Marie-Tooth disease 2D (CMT2D) and distal hereditary motor neuropathy type V (dHMN-V)., These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system., Here, we report the identification of four disease-associated missense mutations in the glycyl tRNA synthetase gene in families with CMT2D and dSMA-V., Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D., Of the many inherited Charcot-Marie-Tooth peripheral neuropathies, type 2D (CMT2D) is caused by dominant point mutations in the gene GARS, encoding glycyl tRNA synthetase (GlyRS)., Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS), Charcot-Marie-Tooth disease type 2D is a hereditary axonal and glycyl-tRNA synthetase (GARS)-associated neuropathy that is caused by a mutation in GARS, Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase, These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system, A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement., Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS). , Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D. , An ENU-induced mutation in mouse glycyl-tRNA synthetase (GARS) causes peripheral sensory and motor phenotypes creating a model of Charcot-Marie-Tooth type 2D peripheral neuropathy., We previously implicated mutations in the gene encoding glycyl-tRNA synthetase (GARS) as the cause of CMT2D and dSMA-V. , An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model., Charcot-Marie-Tooth disease type 2D is a hereditary axonal and glycyl-tRNA synthetase (GARS)-associated neuropathy that is caused by a mutation in GARS. , Dominant mutations in GARS, encoding the essential enzyme glycyl-tRNA synthetase (GlyRS), result in a form of Charcot-Marie-Tooth disease, type 2D (CMT2D), predominantly characterized by lower motor nerve degeneration. , Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS). In addition to GARS, mutations in three other tRNA synthetase genes cause similar neuropathies, although the underlying mechanisms are not fully understood., These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease,, Charcot-Marie-Tooth disease type 2D (CMT2D) is an autosomal-dominant axonal peripheral neuropathy characterized by impaired motor and sensory function in the distal extremities. Mutations in the glycyl-tRNA synthetase (GARS) gene cause CMT2D., Of the many inherited Charcot-Marie-Tooth peripheral neuropathies, type 2D (CMT2D) is caused by dominant point mutations in the gene GARS, encoding glycyl tRNA synthetase (GlyRS)., Charcot-Marie-Tooth disease type 2D (CMT2D) is a dominantly inherited peripheral neuropathy caused by missense mutations in the glycyl-tRNA synthetase gene (GARS)., Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase., Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V., These additional functions may explain why dominant mutations in glycyl-tRNA synthetase (GlyRS) and tyrosyl-tRNA synthetase cause Charcot-Marie-Tooth (CMT) disease, the most common heritable disease of the peripheral nervous system., A novel mutation in glycyl-tRNA synthetase caused Charcot-Marie-Tooth disease type 2D with facial and respiratory muscle involvement., An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model., Glycyl-tRNA synthetase (GARS), which encodes the enzyme responsible for charging tRNA(Gly) with glycine in both the cytoplasm and mitochondria, is implicated to Charcot-Marie-Tooth disease 2D (CMT2D) and distal hereditary motor neuropathy type V (dHMN-V).[SEP]Relations: Charcot-Marie-Tooth disease has relations: disease_protein with GDAP1, disease_protein with GDAP1, disease_protein with GDAP1, disease_protein with GDAP1, disease_protein with LMNA, disease_protein with LMNA, disease_protein with LMNA, disease_protein with LMNA, disease_protein with PNPLA6, disease_protein with PNPLA6. Definitions: glycyl tRNA synthetase defined as following: An enzyme that activates glycine with its specific transfer RNA. EC 6.1.1.14.. mitochondria defined as following: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed). Charcot-Marie-Tooth disease type 2D defined as following: Charcot-Marie-Tooth disease inherited in an autosomal dominant pattern. It is caused by mutations in the GARS gene. It results in axonal peripheral neuropathy.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. neuropathy defined as following: A disorder affecting the cranial nerves or the peripheral nervous system. It manifests with pain, tingling, numbness, and muscle weakness. It may be the result of physical injury, toxic substances, viral diseases, diabetes, renal failure, cancer, and drugs.. Charcot-Marie-Tooth disease defined as following: A hereditary motor and sensory neuropathy transmitted most often as an autosomal dominant trait and characterized by progressive distal wasting and loss of reflexes in the muscles of the legs (and occasionally involving the arms). Onset is usually in the second to fourth decade of life. This condition has been divided into two subtypes, hereditary motor and sensory neuropathy (HMSN) types I and II. HMSN I is associated with abnormal nerve conduction velocities and nerve hypertrophy, features not seen in HMSN II. (Adams et al., Principles of Neurology, 6th ed, p1343). distal hereditary motor neuropathy type V defined as following: A rare autosomal dominant distal hereditary motor neuropathy disease characterized by muscle weakness and wasting predominantly affecting the hands, in particular the thenar and first dorsal interosseus muscles, and/or marked foot deformity and gait disturbance. Sensation is normal, although reduced response to vibration has been described. The disease is slowly progressive with an age of onset within the first few decades of life.. 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). CMT defined as following: brand name of choline magnesium trisalicylate. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. point mutations defined as following: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.. 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.. glycyl-tRNA synthetase gene defined as following: Human GARS1 wild-type allele is located in the vicinity of 7p14.3 and is approximately 39 kb in length. This allele, which encodes glycine-tRNA ligase protein, is involved in the synthesis of glycyl-tRNA. Mutation of the gene is associated with type 2D Charcot-Marie-Tooth disease and distal hereditary motor neuropathy, type Va..", "label": "yes"}
{"id": "converted_4001", "sentence1": "Should nerinetide be used for treatment of ischaemic stroke?", "sentence2": "337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups., INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo.[SEP]Definitions: ischaemic stroke defined as following: An acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of brain tissue..", "label": "no"}
{"id": "converted_4100", "sentence1": "Are synonymous sites in primates and rodents functionally constrained?", "sentence2": "To resolve this contradiction between expectations and observations, we used processed pseudogenes as a model for strict neutral evolution, and estimated selective constraint on synonymous sites using the rate of substitution at pseudosynonymous and pseudononsynonymous sites in pseudogenes as the neutral expectation. After controlling for the effects of GC content, our results were similar to those from previous studies, i.e., synonymous sites in primates exhibited evidence for higher selective constraint that those in rodents. Specifically, our results indicated that in primates up to 24% of synonymous sites could be under purifying selection, while in rodents synonymous sites evolved neutrally. [SEP]Definitions: rodents defined as following: A mammalian order which consists of 29 families and many genera.. 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.. substitution defined as following: Definition: Indicates that the subject Act has undergone or should undergo substitution of a type indicated by Act.code.
Rationale: Used to specify \"allowed\" substitution when creating orders, \"actual\" susbstitution when sending events, as well as the reason for the substitution and who was responsible for it.
. primates defined as following: An order of mammals consisting of more than 300 species that include LEMURS; LORISIDAE; TARSIERS; MONKEYS; and HOMINIDS. They are characterized by a relatively large brain when compared with other terrestrial mammals, forward-facing eyes, the presence of a CALCARINE SULCUS, and specialized MECHANORECEPTORS in the hands and feet which allow the perception of light touch..", "label": "no"}
{"id": "converted_2433", "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).
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.
, 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: 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, drug_protein with AKT1, drug_protein with AKT1. Definitions: peripheral blood mononuclear cells defined as following: A peripheral blood cell with a single nucleus. This category includes lymphocytes and monocytes.. hematologic defined as following: Pertaining to or related to the blood and blood-forming organs.. lymphopenia defined as following: An abnormally small number of lymphocytes in the circulating blood.. lomustine defined as following: An alkylating agent of value against both hematologic malignancies and solid tumors.. temsirolimus defined as following: An ester analog of rapamycin. Temsirolimus binds to and inhibits the mammalian target of rapamycin (mTOR), resulting in decreased expression of mRNAs necessary for cell cycle progression and arresting cells in the G1 phase of the cell cycle. mTOR is a serine/threonine kinase which plays a role in the PI3K/AKT pathway that is upregulated in some tumors.. cilengitide defined as following: A cyclic Arg-Gly-Asp peptide with potential antineoplastic activity. Cilengitide binds to and inhibits the activities of the alpha(v)beta(3) and alpha(v)beta(5) integrins, thereby inhibiting endothelial cell-cell interactions, endothelial cell-matrix interactions, and angiogenesis. (NCI04). toxicities defined as following: The finding of bodily harm due to the poisonous effects of something.. 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.. 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.. 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.. hypophosphatemia defined as following: A condition of an abnormally low level of PHOSPHATES in the blood.. glioblastomas defined as following: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.. temozolomide defined as following: A dacarbazine derivative that is used as an alkylating antineoplastic agent for the treatment of MALIGNANT GLIOMA and MALIGNANT MELANOMA.. 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). 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.. death defined as following: Irreversible cessation of all bodily functions, manifested by absence of spontaneous breathing and total loss of cardiovascular and cerebral functions.. tumors defined as following: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.. bevacizumab defined as following: An anti-VEGF humanized murine monoclonal antibody. It inhibits VEGF RECEPTORS and helps to prevent PATHOLOGIC ANGIOGENESIS.. seizures defined as following: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or \"seizure disorder.\".", "label": "no"}
{"id": "converted_347", "sentence1": "Could the Menzerath-Altmann law be proved mathematically trivial in genomes?", "sentence2": "Here we review the statistical foundations of that test and consider three non-parametric tests based upon different correlation metrics and one parametric test to evaluate if Z ∼ 1/X in genomes. The most powerful test is a new non-parametric one based upon the correlation ratio, which is able to reject Z ∼ 1/X in nine out of 11 taxonomic groups and detect a borderline group. Rather than a fact, Z ∼ 1/X is a baseline that real genomes do not meet. The view of Menzerath-Altmann law as inevitable is seriously flawed., The view of Menzerath-Altmann law as inevitable is seriously flawed., The view of Menzerath-Altmann law as inevitable is seriously flawed., The view of Menzerath-Altmann law as inevitable is seriously flawed.[SEP]Relations: Increased upper to lower segment ratio has relations: disease_phenotype_positive with Turner syndrome due to structural X chromosome anomalies, disease_phenotype_positive with Turner syndrome due to structural X chromosome anomalies, disease_phenotype_positive with Aarskog-Scott syndrome, X-linked, disease_phenotype_positive with Aarskog-Scott syndrome, X-linked, disease_phenotype_positive with Turner syndrome, disease_phenotype_positive with Turner syndrome, disease_phenotype_positive with mosaic monosomy X, disease_phenotype_positive with mosaic monosomy X, disease_phenotype_positive with monosomy X, disease_phenotype_positive with monosomy X. Definitions: genomes defined as following: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA..", "label": "yes"}
{"id": "converted_2347", "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.. respiratory tract infections defined as following: Invasion of the host RESPIRATORY SYSTEM by microorganisms, usually leading to pathological processes or diseases.. 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.. 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.. 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.. respiratory infections defined as following: Invasion of the host RESPIRATORY SYSTEM by microorganisms, usually leading to pathological processes or diseases..", "label": "yes"}
{"id": "converted_2455", "sentence1": "Is LDB1-mediated enhancer looping dependent on cohesin?", "sentence2": "LDB1-mediated enhancer looping can be established independent of mediator and cohesin., Moreover, ENCODE data and our chromatin immunoprecipitation results indicate that cohesin is almost completely absent from validated and predicted LDB1-regulated erythroid enhancer-gene pairs. Thus, lineage specific factors largely mediate enhancer-promoter looping in erythroid cells independent of mediator and cohesin., Moreover, ENCODE data and our chromatin immunoprecipitation results indicate that cohesin is almost completely absent from validated and predicted LDB1-regulated erythroid enhancer-gene pairs., Moreover, ENCODE data and our chromatin immunoprecipitation results indicate that cohesin is almost completely absent from validated and predicted LDB1-regulated erythroid enhancer-gene pairs., LDB1-mediated enhancer looping can be established independent of mediator and cohesin.[SEP]Definitions: ENCODE defined as following: To assign a code to represent data.. erythroid cells defined as following: The series of cells in the red blood cell lineage at various stages of differentiation..", "label": "no"}
{"id": "converted_4691", "sentence1": "Is HYDIN (Hydrocephalus-inducing protein homolog) an axonemal protein?", "sentence2": "Hydin was recently identified as an axonemal protein; however, its function is as yet unknown., precise axonemal location of hydin, a protein that, when mutated, causes hydrocephalus, and defined a unique role for hydin in ciliary motility.[SEP]Relations: Hydrocephalus has relations: disease_phenotype_positive with isotretinoin-like syndrome, disease_phenotype_positive with isotretinoin-like syndrome, disease_phenotype_positive with methylmalonic aciduria/acidemia and homocystinuria, disease_phenotype_positive with methylmalonic aciduria/acidemia and homocystinuria, disease_phenotype_positive with methylmalonic acidemia with homocystinuria, disease_phenotype_positive with methylmalonic acidemia with homocystinuria, disease_phenotype_positive with Noonan syndrome-like disorder with loose anagen hair, disease_phenotype_positive with Noonan syndrome-like disorder with loose anagen hair, drug_effect with Glatiramer, drug_effect with Glatiramer. Definitions: 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.. hydrocephalus defined as following: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, INTRACRANIAL HYPERTENSION; HEADACHE; lethargy; URINARY INCONTINENCE; and ATAXIA..", "label": "yes"}
{"id": "converted_4488", "sentence1": "Is Algenpantucel-L effective for pancreatic cancer?", "sentence2": " Median (IQR) overall survival was 14.9 (12.2-17.8) months in the standard group (N=158) and 14.3 (12.6-16.3) months in the experimental group (N = 145) (hazard ratio [HR] 1.02, 95% CI 0.66-1.58; P = 0.98). Median progression-free survival was 13.4 months in the standard group and 12.4 months in the experimental group (HR 1.33, 95% CI 0.72-1.78; P = 0.59). Grade 3 or higher adverse events occurred in 105 of 140 patients (75%) in the standard group and in 115 of 142 patients (81%) in the experimental group (P > 0.05).CONCLUSIONS: Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiation., CONCLUSIONS: The addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival. A multi-institutional, phase 3 study is ongoing, CONCLUSIONS: The addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve surviva, CONCLUSIONS: Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiatio[SEP]Relations: malignant exocrine pancreas neoplasm has relations: disease_disease with pancreatoblastoma, disease_disease with pancreatoblastoma, disease_disease with exocrine pancreatic carcinoma, disease_disease with exocrine pancreatic carcinoma, disease_disease with pancreatic exocrine neoplasm, disease_disease with pancreatic exocrine neoplasm, disease_disease with pancreatic intraductal papillary-mucinous neoplasm, disease_disease with pancreatic intraductal papillary-mucinous neoplasm, disease_disease with malignant pancreatic neoplasm, disease_disease with malignant pancreatic neoplasm. Definitions: pancreatic cancer defined as following: A primary or metastatic malignant tumor involving the pancreas. Representative examples include carcinoma and lymphoma.. HR defined as following: The rapid, localized death of plant cells in response to invasion by a pathogen. [ISBN:0582227089]. PDAC defined as following: A rare clinical entity including as main characteristics anophthalmia or severe microphthalmia, and pulmonary hypoplasia or aplasia. Only five cases have been reported so far, two of who were siblings. In the three nonfamilial cases, unilateral pulmonary agenesis and microphthalmia were associated with diaphragmatic hernia and pulmonary vessel agenesis. It has been suggested that two different entities can be distinguished: on one hand, the association of anophthalmia-pulmonary hypoplasia with/without anomalies of the face, heart, spleen and uterus, which may be due to a putative autosomal recessive gene with pleiotropic effects; on the other hand, a sporadic association including pulmonary hypoplasia, anophthalmia, unilateral diaphragmatic defect and agenesis of the pulmonary trunk, which may represent the expression of a developmental field defect. There is evidence that syndromic microphthalmia- is caused by homozygous or compound heterozygous mutation in the STRA6 gene on chromosome 15q24..", "label": "no"}
{"id": "converted_2315", "sentence1": "Is propranolol used for treatment of infantile hemangioma?", "sentence2": "Low-dose propranolol for infantile hemangioma of the head and neck: Analysis of 23 consecutive patients., BACKGROUND: More and more infantile hemangiomas (IH) are being treated with propranolol, but the effectiveness, dosage, and treatment course are still in dispute., CONCLUSIONS: Low-dose propranolol appears to be effective and safe for IH, especially for those patients previously treated with corticosteroid and who had no response or severe side-effects., Cardiovascular Profile of Propranolol after Multiple Dosing in Infantile Hemangioma., Propranolol is becoming the treatment of choice for complicated infantile hemangioma., In conclusion, propranolol 2 mg/kg of body weight daily causes a statistically though not clinically relevant decrease in blood pressure and heart rate in cardially healthy infants affected by infantile hemangioma. , Importance: Propranolol hydrochloride has become the primary medical treatment for problematic infantile hemangioma; however, the expression of propranolol's target receptors during growth, involution, and treatment of hemangioma remains unclear., BACKGROUND: Infantile hemangiomas (IHs) are the most common benign vascular tumors of childhood. Propranolol is an effective drug in treating IH. , Ultrasonography as an objective tool for assessment of infantile hemangioma treatment with propranolol., CONCLUSION: Ultrasonographic measurements contribute to demonstrate tumor regression and IH response to propranolol., Propranolol treatment was recently reported to be successful for the management of severe infantile hemangioma., We conclude that the initial use of propranolol as the sole treatment for infantile airway hemangioma is promising., Propranolol has been proposed for the treatment of infantile hemangiomas., Propranolol therapy is changing the treatment paradigm for infantile hemangioma., Propranolol has been successfully used recently in a limited number of children with Infantile hemangioma., Propranolol has been proposed for the treatment of infantile hemangiomas., CONCLUSIONS This is the first report of successful therapy of an intracranial infantile hemangioma with propranolol., PURPOSE The successful use of nadolol as an alternative to propranolol therapy in three cases of infantile hemangioma is reported., Propranolol has been used successfully in a limited number of children with infantile hemangiomas., CONCLUSIONS High-dose Propranolol is very effective in the treatment of infantile hemangioma with minor side effects and short disease period., Propranolol is novel and safe medication for treatment of infantile hemangioma., Propranolol is the only Food and Drug Administration approved therapy for treatment of patients with this vascular anomaly and should be considered first-line therapy for genital infantile hemangiomas., CONCLUSION Propranolol may be a promising therapeutic modality for infantile hemangioma., Propranolol, which is often used to treat cutaneous infantile hemangiomas, is not currently standard treatment for intracranial infantile hemangiomas., Preliminary results of propranolol treatment for patients with infantile hemangioma., Propranolol therapy is changing the treatment paradigm for infantile hemangioma., Propranolol should be considered as a first-line treatment of infantile hemangiomas.., Propranolol, a non-selective beta-blocker, has recently been introduced as a treatment for infantile hemangiomas.[SEP]Relations: Propranolol has relations: contraindication with muscular disease, contraindication with muscular disease, contraindication with bronchial disease, contraindication with bronchial disease, drug_drug with Propiomazine, drug_drug with Propiomazine, contraindication with neonatal jaundice, contraindication with neonatal jaundice, contraindication with myopathy, contraindication with myopathy. Definitions: drug defined as following: Any natural, endogenously-derived, synthetic or semi-synthetic compound with pharmacologic activity. A pharmacologic substance has one or more specific mechanism of action(s) through which it exerts one or more effect(s) on the human or animal body. They can be used to potentially prevent, diagnose, treat or relieve symptoms of a disease. Formulation specific agents and some combination agents are also classified as pharmacologic substances.. corticosteroid defined as following: HORMONES produced by the ADRENAL CORTEX, including both steroid and peptide hormones. The major hormones produced are HYDROCORTISONE and ALDOSTERONE.. nadolol defined as following: A non-selective beta-adrenergic antagonist with a long half-life, used in cardiovascular disease to treat arrhythmias, angina pectoris, and hypertension. Nadolol is also used for MIGRAINE DISORDERS and for tremor.. Infantile hemangiomas defined as following: A dull red, firm, dome-shaped hemangioma, sharply demarcated from surrounding skin, usually located on the head and neck, which grows rapidly and generally undergoes regression and involution without scarring. It is caused by proliferation of immature capillary vessels in active stroma, and is usually present at birth or occurs within the first two or three months of life. (Dorland, 27th ed). IH defined as following: Isolated hemihyperplasia is a rare overgrowth syndrome characterized by an asymmetric regional body overgrowth, involving at least one limb, and associated with an increased risk of developing embryonal tumors, principally nephroblastoma (see this term) and hepoblastoma.. IHs defined as following: Syndrome with characteristics of congenital ichthyosis and hypotrichosis. It has been described in three members of a consanguineous Arab Israeli family. The syndrome is transmitted as an autosomal recessive trait and is caused by a missense mutation in the ST14 gene, encoding the recently identified protease, matriptase on chromosome 11q24. Analysis of skin samples from the patients suggests that this enzyme plays a role in epidermal desquamation.. infantile hemangioma defined as following: A dull red, firm, dome-shaped hemangioma, sharply demarcated from surrounding skin, usually located on the head and neck, which grows rapidly and generally undergoes regression and involution without scarring. It is caused by proliferation of immature capillary vessels in active stroma, and is usually present at birth or occurs within the first two or three months of life. (Dorland, 27th ed). hydrochloride defined as following: A salt that is comprised of a hydrogen and chloride ion that can be linked to a base form of a drug making it water-soluble. (NCI). intracranial defined as following: Administration of a drug within the skull.. hemangioma defined as following: A vascular anomaly due to proliferation of BLOOD VESSELS that forms a tumor-like mass. The common types involve CAPILLARIES and VEINS. It can occur anywhere in the body but is most frequently noticed in the SKIN and SUBCUTANEOUS TISSUE. (from Stedman, 27th ed, 2000). Low-dose defined as following: A reduced quantity of a therapeutic agent prescribed to be taken at one time or at stated intervals.. propranolol defined as following: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.. beta-blocker defined as following: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety..", "label": "yes"}
{"id": "converted_642", "sentence1": "Are Alu elements transcribed?", "sentence2": "Alu RNAs in the human transcriptome, Alu elements can be transcribed in two different ways, by two independent polymerases, 'Free Alu RNAs' are transcribed by Pol III from their own promoter, 'embedded Alu RNAs' are transcribed by Pol II as part of protein- and non-protein-coding RNAs, Recent studies have demonstrated that both free and embedded Alu RNAs play a major role in post transcriptional regulation of gene expression, Alu RNAs transcribed from these elements are present at low levels at normal cell growth but various stress conditions increase their abundance, Alu RNAs are known to bind the cognate proteins SRP9/14, Increased level of polymerase III transcribed Alu RNA in hepatocellular carcinoma tissue, we used primer extension analysis to determine the level of polymerase III directed Alu RNA and found an increased expression of Alu RNA in hepatocellular carcinoma, Widespread RNA editing of embedded alu elements in the human transcriptome, Transcribed Alu sequences can alter splicing patterns by generating new exons, In the vast majority of edited RNAs, A-to-I substitutions are clustered within transcribed sense or antisense Alu sequences, Alu-associated RNA editing may be a mechanism for marking nonstandard transcripts, not destined for translation, the case of transcribed Alus, Differential levels of Alu RNA during different conditions of stress also await clear functional understanding, Alu expression in human cell lines and their retrotranspositional potential, Alu expression likely varies by cell type, growth conditions and transformation state, The vast majority of Alu loci potentially transcribed by RNA pol III lack important sequence features for retrotransposition and the majority of potentially active Alu loci in the genome (scored high ERP) belong to young Alu subfamilies, We suggest that the genomic sequences upstream from most Alu elements and 7SL pseudogenes do not contain this element, and consequently that only a small subset of such sequences can be transcribed in vivo., These similarities suggest that some Alu family sequences are mobile genetic elements that can transpose to new chromosomal loci using as an intermediate a cDNA copy of an RNA transcribed from the Alu family element by RNA polymerase III., Primate and rodent genomes are populated with hundreds of thousands copies of Alu and B1 elements dispersed by retroposition, i.e., by genomic reintegration of their reverse transcribed RNAs., Members of this family are readily transcribed in vitro by RNA polymerase III, but RNA corresponding to only a small sub-set of Alu elements has been found in vivo., Alu interspersed repetitive elements possess internal RNA polymerase III promoters which are strongly transcribed in vitro, yet these elements are nearly silent in somatic cells., The amplification of genomic Alu elements by retroposition, i.e. by reintegration of reverse-transcribed RNA, suggests that Alu RNA plays an important role in this process., We report enzymatic studies of the secondary structure of Alu RNAs transcribed in vitro from two recently retroposed Alu elements., The results of this study indicate that Alu and 7SL RNA gene sequences interact with cellular factors that are important for HeLa cell proliferation and suggest that these pol III-transcribed elements may be involved in the regulation of cellular growth., Then we used primer extension analysis to determine the level of polymerase III directed Alu RNA and found an increased expression of Alu RNA in hepatocellular carcinoma, Alu interspersed repetitive elements possess internal RNA polymerase III promoters which are strongly transcribed in vitro, yet these elements are nearly silent in somatic cells, 'Free Alu RNAs' are transcribed by Pol III from their own promoter, while 'embedded Alu RNAs' are transcribed by Pol II as part of protein- and non-protein-coding RNAs, We report enzymatic studies of the secondary structure of Alu RNAs transcribed in vitro from two recently retroposed Alu elements, Transcribed Alu sequences can alter splicing patterns by generating new exons, but other impacts of intragenic Alu elements on their host RNA are largely unexplored, Both 7SL genes and Alu elements are transcribed by RNA polymerase III, and we show here that the internal 7SL promoter lies within the Alu-like part of the 7SL gene, Each group revealed a divergent pattern of transcribed Alu elements[SEP]Relations: DNA secondary structure binding has relations: molfunc_protein with RAD51AP1, molfunc_protein with RAD51AP1, molfunc_protein with CLSPN, molfunc_protein with CLSPN. promoter clearance from RNA polymerase I promoter has relations: bioprocess_bioprocess with promoter clearance during DNA-templated transcription, bioprocess_bioprocess with promoter clearance during DNA-templated transcription. RNA polymerase III complex has relations: cellcomp_protein with POLR2L, cellcomp_protein with POLR2L, cellcomp_protein with POLR3G, cellcomp_protein with POLR3G. Definitions: sequences defined as following: The sequence of nucleotide residues along a DNA chain.. 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.. Pol II defined as following: A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure and transcribes DNA into RNA. It has different requirements for cations and salt than RNA polymerase I and is strongly inhibited by alpha-amanitin. EC 2.7.7.6.. Alu elements defined as following: The Alu sequence family (named for the restriction endonuclease cleavage enzyme Alu I) is the most highly repeated interspersed repeat element in humans (over a million copies). It is derived from the 7SL RNA component of the SIGNAL RECOGNITION PARTICLE and contains an RNA polymerase III promoter. Transposition of this element into coding and regulatory regions of genes is responsible for many heritable diseases.. genomic defined as following: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.. ERP defined as following: Fiberoptic endoscopy designed for duodenal observation and cannulation of VATER'S AMPULLA, in order to visualize the pancreatic and biliary duct system by retrograde injection of contrast media. Endoscopic (Vater) papillotomy (SPHINCTEROTOMY, ENDOSCOPIC) may be performed during this procedure.. 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). 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.. 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.. RNA editing defined as following: A process that changes the nucleotide sequence of mRNA from that of the DNA template encoding it. Some major classes of RNA editing are as follows: 1, the conversion of cytosine to uracil in mRNA; 2, the addition of variable number of guanines at pre-determined sites; and 3, the addition and deletion of uracils, templated by guide-RNAs (RNA, GUIDE, KINETOPLASTIDA).. promoter defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. exons defined as following: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.. RNA polymerase III defined as following: A DNA-dependent RNA polymerase present in bacterial, plant, and animal cells. It functions in the nucleoplasmic structure where it transcribes DNA into RNA. It has specific requirements for cations and salt and has shown an intermediate sensitivity to alpha-amanitin in comparison to RNA polymerase I and II.. cDNA defined as following: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.. primer defined as following: Short DNA oligonucleotide chains used to prime DNA (and in some cases RNA) synthesis.. human defined as following: Members of the species Homo sapiens.. genome defined as following: Anatomical set of genes in all the chromosomes.. somatic cells defined as following: Nucleated cell which has one or more diploid sets (46 pairs) of chromosomes.. secondary structure defined as following: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to ALPHA-HELICES; BETA-STRANDS (which align to form BETA-SHEETS), or other types of coils. This is the first folding level of protein conformation..", "label": "yes"}
{"id": "converted_1242", "sentence1": "Is nimodipine recommended for prevention of vasospasm in aneurysmal subarachnoid hemorrhage patients?", "sentence2": "This article discusses some of these unresolved issues, including the use of medications such as nimodipine, antifibrinolytics, statins, and magnesium; coiling or clipping for aneurysm securement; and the prevention and treatment of potential complications., The results of this study were as follows: nimodipine demonstrated benefit following aneurysmal SAH; other calcium channel blockers, including nicardipine, do not provide unequivocal benefit; triple-H therapy, fasudil, transluminal balloon angioplasty, thrombolytics, endothelin receptor antagonists, magnesium, statins, and miscellaneous therapies such as free radical scavengers and antifibrinolytics require additional study., The present results suggest that fasudil is equally or more effective than nimodipine for the prevention of cerebral vasospasm and subsequent ischemic injury in patients undergoing surgery for SAH., Three studies (2 meta-analyses and 1 randomized controlled trial) demonstrated that nimodipine use confers benefits (reduced morbidity and mortality) for patients with aneurysmatic subarachnoid hemorrhage., Nimodipine is the only preventative treatment that can be recommended., Nimodipine (Nimotop), HMG Co-A reductase inhibitor (statins) and enoxaparin (Lovenox) were the only drugs with level-1 evidence available for the treatment of vasospasm from aneurysmal subarachnoid hemorrhage as defined by the US Preventative Services Task Force., The calcium antagonist nimodipine has been shown to reduce the incidence of ischemic complications following aneurysmal subarachnoid hemorrhage (SAH)., There was no significant difference in the incidence of DINDs (28 vs 30% in the peroral and intravenous groups, respectively) or middle cerebral artery blood flow velocities (> 120 cm/second, 50 vs 45%, respectively)., Clinical outcome according to the Glasgow Outcome Scale was the same in both groups, and there was no difference in the number of patients with new infarctions on MR imaging., The results suggest that there is no clinically relevant difference in efficacy between peroral and intravenous administration of nimodipine in preventing DINDs or cerebral vasospasm following SAH., the risk of delayed cerebral ischemia is reduced with nimodipine and avoiding hypovolemia, A recommendations (standard) for the prophylaxis and treatment of cerebral vasospasm with oral Nimodipine in good grade patients., Of the 75 patients initially considered for active treatment, 83% underwent surgery within 48 hours of rupture, all received nimodipine, 16% received tissue plasminogen activator to lyse subarachnoid or intraventricular clots, 40% underwent hypertensive treatment, and 7% underwent transluminal balloon angioplasty for vasospasm., All patients with aneurysmal SAH should be treated with the calcium antagonist nimodipine, and in certain circumstances patients should receive anticonvulsants., The following review gives an account of pathophysiological mechanisms; the importance of treatment with calcium antagonists, hypervolaemic haemodilution, and induced arterial hypertension is discussed in light of the current literature., Seven placebo-controlled clinical studies have shown that nimodipine improves the outcome of patients with severe neurological damage due to cerebral vasospasm., In a series of 100 individuals with a ruptured supratentorial aneurysm, who were subjected to aneurysm operation in the acute stage and who subsequently received intravenous treatment with the calcium channel blocker nimodipine, the occurrence of DID with FND was reduced to 5%., There are many possible successful treatment options for preventing vasospasm, delayed ischemic neurologic deficits, and poor neurologic outcome following aneurysmal subarachnoid hemorrhage; however, further multicenter RCTs need to be performed to determine if there is a significant benefit from their use. Nimodipine is the only treatment that provided a significant benefit across multiple studies., Absence of symptomatic vasospasm, occurrence of low density areas associated with vasospasm on CT, and occurrence of adverse events were similar between the two groups. The clinical outcomes were more favorable in the fasudil group than in the nimodipine group (p = 0.040). The proportion of patients with good clinical outcome was 74.5% (41/55) in the fasudil group and 61.7% (37/60) in the nimodipine group., Cerebral vasospasm is the classic cause of delayed neurological deterioration leading to cerebral ischemia and infarction, and thus, poor outcome and occasionally death, after aneurysmal subarachnoid hemorrhage (SAH). Advances in diagnosis and treatment, principally nimodipine, intensive care management, hemodynamic manipulations, and endovascular neuroradiology procedures, have improved the prospects for these patients, but outcomes remain disappointing., Cerebral vasospasm is the classic cause of delayed neurological deterioration after aneurysmal subarachnoid hemorrhage, leading to cerebral ischemia and infarction, and thus to poor outcome and occasionally death. Advances in diagnosis and treatment-principally the use of nimodipine, intensive care management, hemodynamic manipulations and endovascular neuroradiology procedures-have improved the prospects for these patients, but outcomes remain disappointing., Cerebral vasospasm and delayed cerebral ischemia remain common complications of aneurysmal subarachnoid hemorrhage (SAH), and yet therapies for cerebral vasospasm are limited. Despite a large number of clinical trials, only calcium antagonists have strong evidence supporting their effectiveness., The only proven therapy for vasospasm is nimodipine., nimodipine is indicated after SAH and tirilazad is not effective., Fasudil hydrochloride and nimodipine both showed inhibitory effects on cerebral vasospasm. The incidence of symptomatic vasospasm was five of 33 patients in the fasudil group and nine of 32 patients in the nimodipine group. Good recovery evaluated by the Glasgow Outcome Scale was achieved by 23 of 33 patients in the fasudil group and 19 of 34 patients in the nimodipine group. Both drugs significantly improved consciousness levels and neurological deficits such as aphasia. However, fasudil hydrochloride improved motor disturbance more than nimodipine.[SEP]Relations: Nimodipine has relations: drug_effect with Gastrointestinal hemorrhage, drug_effect with Gastrointestinal hemorrhage, drug_drug with Nitroprusside, drug_drug with Nitroprusside, drug_effect with Erythema, drug_effect with Erythema, drug_drug with Nitroaspirin, drug_drug with Nitroaspirin, drug_drug with Chlorpropamide, drug_drug with Chlorpropamide. Definitions: Lovenox defined as following: brand name of enoxaparin. hydrochloride defined as following: A salt that is comprised of a hydrogen and chloride ion that can be linked to a base form of a drug making it water-soluble. (NCI). hypovolemia defined as following: An abnormally low volume of blood circulating through the body. It may result in hypovolemic shock (see SHOCK).. Nimodipine defined as following: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure.. nicardipine defined as following: A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents.. enoxaparin defined as following: Low-molecular-weight fragment of heparin, having a 4-enopyranosuronate sodium structure at the non-reducing end of the chain. It is prepared by depolymerization of the benzylic ester of porcine mucosal heparin. Therapeutically, it is used as an antithrombotic agent. (From Merck Index, 11th ed). endothelin receptor antagonists defined as following: Compounds and drugs that bind to and inhibit or block the activation of ENDOTHELIN B RECEPTORS.. 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.. SAH defined as following: A Turkic language spoken by the Yakut people in the Sakha Republic in the Russian Federation.. infarctions 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.. statins defined as following: Compounds that inhibit HYDROXYMETHYLGLUTARYL COA REDUCTASES. They have been shown to directly lower CHOLESTEROL synthesis.. vasospasm defined as following: spasm of the blood vessels resulting in decrease in their caliber.. cerebral ischemia defined as following: The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).. neurological damage defined as following: Traumatic injuries to the brain, cranial nerves, spinal cord, autonomic nervous system, or neuromuscular system, including iatrogenic injuries induced by surgical procedures.. aphasia defined as following: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia.. neurological deficits defined as following: Loss of movement function.. rupture defined as following: Forcible or traumatic tear or break of an organ or other soft part of the body.. free radical scavengers defined as following: Substances that eliminate free radicals. Among other effects, they protect PANCREATIC ISLETS against damage by CYTOKINES and prevent myocardial and pulmonary REPERFUSION INJURY.. nimodipine defined as following: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure..", "label": "yes"}
{"id": "converted_1274", "sentence1": "Is Fanconi anemia presented as a genetically and clinically heterogeneous disease entity?", "sentence2": "Fanconi anaemia (FA) is a rare, autosomal recessive, genetically complex, DNA repair deficiency syndrome in man. Patients with FA exhibit a heterogeneous spectrum of clinical features. The most significant and consistent phenotypic characteristics are stem cell loss, causing progressive bone marrow failure and sterility, diverse developmental abnormalities and a profound predisposition to neoplasia. To date, 15 genes have been identified, biallelic disruption of any one of which results in this clinically defined syndrome, Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder, Significant phenotypic differences were found. FA-G patients had more severe cytopenia and a higher incidence of leukemia. Somatic abnormalities were less prevalent in FA-C, but more common in the rare groups FA-D, FA-E, and FA-F. In FA-A, patients homozygous for null mutations had an earlier onset of anemia and a higher incidence of leukemia than those with mutations producing an altered protein, Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. At least eight complementation groups (FA-A to FA-H) have been identified, Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease. At least eight complementation groups (FA-A to FA-H) have been identified with their relative prevalence varying among the ethnical backgrounds, Fanconi anemia is a rare autosomal recessive disorder characterized clinically by congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancy. FA cells are sensitive to DNA cross-linking agents. Complementation analysis of FA cells using somatic cell fusion has facilitated the identification of eight complementation groups, suggesting that FA is a genetically heterogeneous disorder. Six genes (FANCA, FANCC, FANCD2, FANCE, FANGF, FANCG) have been cloned so far, Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease., Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease., Among patients with bone marrow failure (BMF) syndrome, some are happened to have underlying Fanconi anemia (FA), a genetically heterogeneous disease, which is characterized by progressive pancytopenia and cancer susceptibility., Fanconi anemia (FA) is a genetically and phenotypically heterogeneous inherited disease., Fanconi anemia is a genetically heterogeneous recessive disease characterized mainly by bone marrow failure and cancer predisposition., INTRODUCTION: Fanconi anemia (FA) is a genetically and phenotypically heterogeneous inherited disease., Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies., Fanconi anemia (FA) is a heterogeneous disease associated with a bone marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents., Fanconi anemia is a genetically heterogeneous chromosomal instability syndrome, characterized by multiple congenital anomalies, progressive bone marrow failure, and a predisposition to malignancy., Fanconi anemia (FA) is a heterogeneous disease characterized by spontaneous chromosomal breaks and abnormal DNA repair., Fanconi anemia (FA) is a genetically heterogeneous disease with at least eight genes on the basis of complementation groups (FAA to FAH)., Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder., Fanconi anaemia (FA) is a genetically heterogeneous disease with at least eight complementation groups (A-H)., FA is a genetically heterogeneous disease with at least seven genes so far identified., Fanconi anemia (FA) is an autosomal recessive rare disease characterized by progressive pancytopenia, congenital malformations and predisposition to acute myeloid leukemia., Fanconi anemia is genetically heterogeneous, with at least eight complementation groups of FA (FAA to FAD2)., Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease, Fanconi anemia (FA), an autosomal recessive disorder characterized by a progressive pancytopenia associated with congenital anomalies and high predisposition to malignancies, is a genetically and clinically heterogeneous disease, The disease is clinically heterogeneous; eight different complementation groups (FA A-H) and, thus, genetic loci have been discovered, The hereditary genetic disorder Fanconi anemia (FA) belongs to the heterogeneous group of diseases associated with defective DNA damage repair, The clinical manifestations of FA are heterogeneous, but one common outcome in the majority of patients is the development of life-threatening hematologic disease, Fanconi anemia is a genetically heterogeneous chromosomal breakage disorder exhibiting a high degree of clinical variability, Fanconi anemia (FA) is a genetically heterogeneous chromosomal instability syndrome associated with multiple congenital abnormalities, aplastic anemia, and cancer, Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive syndrome associated with chromosomal instability, hypersensitivity to DNA cross-linking agents, and predisposition to malignancy, Fanconi anemia (FA) is a rare autosomal recessive disease characterized by progressive pancytopenia, congenital malformations, and predisposition to acute myeloid leukemia, Fanconi anemia (FA) is a heterogeneous disease characterized by spontaneous chromosomal breaks and abnormal DNA repair, Fanconi anemia (FA) is a genetically and phenotypically heterogeneous recessive disorder characterized by diverse congenital malformations, progressive pancytopenia and predisposition to both hematologic malignancies and solid tumors, Fanconi anemia is a genetically heterogeneous chromosomal instability syndrome, characterized by multiple congenital anomalies, progressive bone marrow failure, and a predisposition to malignancy[SEP]Relations: Fanconi anemia has relations: disease_disease with congenital anemia, disease_disease with congenital anemia, disease_disease with genetic skin disease, disease_disease with genetic skin disease. Fanconi anemia complementation group has relations: disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia, disease_disease with Fanconi anemia. Definitions: FANCA defined as following: Fanconi anemia caused by mutations of the FANCA gene. FANCA gene mutations are the most common cause of Fanconi anemia. This gene provides instructions for making a protein that is involved in the Fanconi anemia (FA) pathway.. autosomal recessive disorder defined as following: An inherited disorder manifested only when two copies of a mutated gene are present.. cancer defined as following: A malignant tumor at the original site of growth.. acute myeloid leukemia defined as following: Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.. FANCC defined as following: Fanconi anemia caused by mutations of the FANCC gene. This gene provides instructions for making a protein that delays the onset of apoptosis and promotes homologous recombination repair of damaged DNA.. FAH defined as following: Human FANCA wild-type allele is located in the vicinity of 16q24.3 and is approximately 79 kb in length. This allele, which encodes Fanconi anemia group A protein, may play a role in the regulation of both DNA repair and the cell cycle. Mutation of the gene is associated with Fanconi anemia.. FANCD2 defined as following: Fanconi anemia caused by mutations of the FANCD2 gene. This gene is involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing.. leukemia defined as following: A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006). hematologic malignancies defined as following: Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.. hypersensitivity defined as following: Heightened emotional reactivity to environmental stimuli, including emotions of others. [PMID:23250816]. 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.. congenital malformations defined as following: Malformations of organs or body parts during development in utero.. pancytopenia defined as following: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets.. genetic loci defined as following: Specific regions that are mapped within a GENOME. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of CHROMOSOME 6. Many well known genetic loci are also known by common names that are associated with a genetic function or HEREDITARY DISEASE.. FANCG defined as following: Fanconi anemia caused by mutations of the FANCG gene.. FANCE defined as following: Fanconi anemia caused by mutations of the FANCE gene. This is a protein coding gene. It is required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2.. malignancies defined as following: A tumor composed of atypical neoplastic, often pleomorphic cells that invade other tissues. Malignant neoplasms often metastasize to distant anatomic sites and may recur after excision. The most common malignant neoplasms are carcinomas, Hodgkin and non-Hodgkin lymphomas, leukemias, melanomas, and sarcomas.. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. autosomal recessive defined as following: A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). [HPO:probinson]. aplastic anemia defined as following: A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.. mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. hematologic disease defined as following: Disorders of the blood and blood forming tissues.. bone marrow failure defined as following: A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat. [DDD:wouwehand, HPO:probinson]. Fanconi anaemia defined as following: Congenital disorder affecting all bone marrow elements, resulting in ANEMIA; LEUKOPENIA; and THROMBOPENIA, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous CHROMOSOME BREAKAGE is a feature of this disease along with predisposition to LEUKEMIA. There are at least 7 complementation groups in Fanconi anemia: FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227650, August 20, 2004). 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.. cytopenia defined as following: A laboratory test result indicating an abnormally low quantity of circulating blood cells.. 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..", "label": "yes"}
{"id": "converted_1057", "sentence1": "Are there clinical trials on stem cells in multiple sclerosis", "sentence2": "Cells are generally given intravenously. Multiple sclerosis, rheumatoid arthritis and lupus have been successfully treated in human clinical trials, Human multipotent mesenchymal stem cell (MSC) therapies are currently being tested in clinical trials for Crohn's disease, multiple sclerosis, graft-versus-host disease, type 1 diabetes, bone fractures, cartilage damage, and cardiac diseases., Based on these results, several small pilot clinical trials in subjects with advanced MS have demonstrated that MSC administration is safe and provided an early signal of clinical effectiveness. The current aim of clinicians and scientists interested in the development of MSC-based strategies for the treatment of MS is to have the ultimate demonstration in large clinical trials that MSC can inhibit CNS inflammation and foster tissue repair, Mesenchymal stem cells (MSC) promote functional recovery in experimental models of central nervous system (CNS) pathology and are currently being tested in clinical trials for stroke, multiple sclerosis and CNS injury., Autologous bone marrow stromal cells (BMSCs) offer significant practical advantages for potential clinical applications in multiple sclerosis (MS). Based on recent experimental data, a number of clinical trials have been designed for the intravenous (IV) and/or intrathecal (ITH) administration of BMSCs in MS patients., Fingolimod is a S1P receptor modulator in MS clinical trials due to systemic anti-inflammatory properties, yet may impact cells within the CNS by crossing the blood-brain barrier., Their development in vitro and their use in vivo in animal models of degenerative neurological disease and recent first efforts in human clinical trials were the topics of a recent international meeting sponsored by the Multiple Sclerosis International Federation and the National Multiple Sclerosis Society on \"Stem Cells & MS: Prospects and Strategies\", Here we discuss key observations and questions emerging from clinical trials of hematopoietic stem cell transplantation for MS, Another possibility to achieve remyelination is the transplantation of myelinating cells into the central nervous system. Proof of principle and demonstration of the functionality were shown in numerous experiments, and a first clinical trial in patients with MS has started, This first trial will show if cell transplantation is a feasible concept in MS and whether the transplanted cells will survive and form new myelin.[SEP]Relations: multiple sclerosis has relations: disease_disease with brain disease, disease_disease with brain disease, disease_disease with multiple sclerosis, susceptibility to, disease_disease with multiple sclerosis, susceptibility to, disease_protein with IL12A, disease_protein with IL12A, disease_protein with SELE, disease_protein with SELE, disease_protein with IL1RN, disease_protein with IL1RN. Definitions: 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.. 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.. human defined as following: Members of the species Homo sapiens.. graft-versus-host disease defined as following: The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION.. MSC defined as following: A naturally occurring organoselenium compound found in many plants, including garlic, onions, and broccoli, with potential antioxidant and chemopreventive activities. Se-Methyl-seleno-L-cysteine (MSC) is an amino acid analogue of cysteine in which a methylselenium moiety replaces the sulphur atom of cysteine. This agent acts as an antioxidant when incorporated into glutathione peroxidase and has been shown to exhibit potent chemopreventive activity in animal models.. 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). Mesenchymal stem cells defined as following: An undifferentiated stromal cell with the ability to develop into the cells that form distinct mesenchymal tissues; such as bone, muscle, connective tissue, blood vessels, and lymphatic tissue.. Fingolimod defined as following: An orally available derivate of myriocin and sphingosine-1-phosphate receptor 1 (S1PR1, S1P1) modulator, with potential anti-inflammatory and immunomodulating activities. Upon oral administration, fingolimod, as a structural analogue of sphingosine, selectively targets and binds to S1PR1 on lymphocytes and causes transient receptor activation followed by S1PR1 internalization and degradation. This results in the sequestration of lymphocytes in lymph nodes. By preventing egress of lymphocytes. fingolimod reduces both the amount of circulating peripheral lymphocytes and the infiltration of lymphocytes into target tissues. This prevents a lymphocyte-mediated immune response and may reduce inflammation. S1PR1, a G-protein coupled receptor, plays a key role in lymphocyte migration from lymphoid tissues. Fingolimod also shifts macrophages to an anti-inflammatory M2 phenotype, and modulates their proliferation, morphology, and cytokine release via inhibition of the transient receptor potential cation channel, subfamily M, member 7 (TRPM7).. 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.. 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). myelin defined as following: The lipid-rich sheath surrounding AXONS in both the CENTRAL NERVOUS SYSTEMS and PERIPHERAL NERVOUS SYSTEM. The myelin sheath is an electrical insulator and allows faster and more energetically efficient conduction of impulses. The sheath is formed by the cell membranes of glial cells (SCHWANN CELLS in the peripheral and OLIGODENDROGLIA in the central nervous system). Deterioration of the sheath in DEMYELINATING DISEASES is a serious clinical problem.. CNS defined as following: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.. lupus defined as following: chronic form of cutaneous lupus erythematosus in which the skin lesions mimic those of the systemic form but in which systemic signs are rare; characterized by the presence of discoid skin plaques showing varying degrees of edema, erythema, scaliness, follicular plugging, and skin atrophy; lesions are surrounded by an elevated erythematous border; the condition typically involves the face and scalp, but widespread dissemination may occur.. cardiac diseases defined as following: Pathological conditions involving the HEART including its structural and functional abnormalities.. stem cells defined as following: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells..", "label": "yes"}
{"id": "converted_1800", "sentence1": "Does Vitamin D induce autophagy?", "sentence2": " 1,25(OH)2D treatment was accompanied by autophagy activation , Autophagy signaling pathway was regulated by vitamin D3, vitamin D induces autophagy, Vitamin D shows promise for the prevention and amelioration of pathologic responses in IBD, an effect that is mediated, at least in part, by the induction and modulation of autophagy.[SEP]Relations: Ergocalciferol has relations: drug_drug with Vitamin D, drug_drug with Vitamin D, contraindication with familial isolated deficiency of vitamin E, contraindication with familial isolated deficiency of vitamin E, drug_protein with VDR, drug_protein with VDR. Cholecalciferol has relations: drug_drug with Vitamin D, drug_drug with Vitamin D, contraindication with familial isolated deficiency of vitamin E, contraindication with familial isolated deficiency of vitamin E. Definitions: vitamin D defined as following: Vitamin D2, a fat-soluble vitamin important for many biochemical processes including the absorption and metabolism of calcium and phosphorus. In vivo, ergocalciferol is formed after sun (ultraviolet) irradiation of plant-derived ergosterol, another form of vitamin D. Ergocalciferol is the form of vitamin D usually found in vitamin supplements. (NCI04). vitamin D3 defined as following: Derivative of 7-dehydroxycholesterol formed by ULTRAVIOLET RAYS breaking of the C9-C10 bond. It differs from ERGOCALCIFEROL in having a single bond between C22 and C23 and lacking a methyl group at C24.. IBD defined as following: Gastrointestinal symptoms characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause.. Vitamin D defined as following: Vitamin D2, a fat-soluble vitamin important for many biochemical processes including the absorption and metabolism of calcium and phosphorus. In vivo, ergocalciferol is formed after sun (ultraviolet) irradiation of plant-derived ergosterol, another form of vitamin D. Ergocalciferol is the form of vitamin D usually found in vitamin supplements. (NCI04).", "label": "yes"}
{"id": "converted_1505", "sentence1": "Is it possible to visualize subtahalamic nucleus by using transcranial ultrasound?", "sentence2": "After measuring thermal effects of TCS and imaging artefact sizes of DBS lead using a skull phantom, we prospectively enrolled 34 patients with DBS of globus pallidus internus, ventro-intermediate thalamic or subthalamic nucleus. TCS had no influence on lead temperature, electrical parameters of DBS device or clinical state of patients. TCS measures of lead coordinates agreed with MRI measures in anterior-posterior and medial-lateral axis. Lead dislocation requiring reinsertion was reliably detected., TCS may therefore become a first-choice modality to monitor lead location., Two pilot studies have demonstrated that the intraoperative visualization with TCS and the TCS-assisted insertion of deep-brain stimulation (DBS) electrodes into the subthalamic nucleus and the globus pallidus interna are feasible and safe provided there is exact knowledge on the extent of electrode TCS imaging artifacts. , Peroperative transcranial sonography for electrode placement into the targeted subthalamic nucleus of patients with Parkinson disease: technical note, The correct anatomic position of the electrode tip could be indirectly assessed thanks to the topographic relationship of the STN with the hyperechogenic substantia nigra and the nucleus ruber., CONCLUSIONS: Transcranial sonography is easily feasible during stereotactic surgery. In combination with the clinical effects of electrostimulation on the symptoms of Parkinson's disease and with stereotactic x-ray images, it enables the assessment and the documentation of the correct position of implanted STN electrodes in real time., After measuring thermal effects of TCS and imaging artefact sizes of DBS lead using a skull phantom, we prospectively enrolled 34 patients with DBS of globus pallidus internus, ventro-intermediate thalamic or subthalamic nucleus, Two pilot studies have demonstrated that the intraoperative visualization with TCS and the TCS-assisted insertion of deep-brain stimulation (DBS) electrodes into the subthalamic nucleus and the globus pallidus interna are feasible and safe provided there is exact knowledge on the extent of electrode TCS imaging artifacts[SEP]Relations: subthalamic nucleus has relations: anatomy_anatomy with nucleus of ventral thalamus, anatomy_anatomy with nucleus of ventral thalamus. medial globus pallidus has relations: anatomy_protein_present with MTPAP, anatomy_protein_present with MTPAP, anatomy_protein_present with PCNP, anatomy_protein_present with PCNP, anatomy_protein_present with CRTAP, anatomy_protein_present with CRTAP, anatomy_protein_present with RNMT, anatomy_protein_present with RNMT. Definitions: TCS defined as following: A hereditary disorder occurring in two forms: the complete form (Franceschetti's syndrome) is characterized by antimongoloid slant of the palpebral fissures, COLOBOMA of the lower lid, MICROGNATHIA and hypoplasia of the ZYGOMATIC ARCHES, and CONGENITAL MICROTIA. It is transmitted as an autosomal trait. The incomplete form (Treacher Collins syndrome) is characterized by the same anomalies in less pronounced degree. It occurs sporadically, but an autosomal dominant mode of transmission is suspected. (Dorland, 27th ed). STN defined as following: Human EEF1A2 wild-type allele is located in the vicinity of 20q13.3 and is approximately 11 kb in length. This allele, which encodes elongation factor 1-alpha 2 protein, is involved in the promotion of protein elongation. The gene is expressed aberrantly at elevated levels in many ovarian cancers.. position defined as following: A reference to the alignment of an object, a particular situation or view of a situation, or the location of an object.. insertion defined as following: Something inserted or to be inserted.. Parkinson's disease defined as following: A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75). subthalamic nucleus defined as following: Lens-shaped structure on the inner aspect of the INTERNAL CAPSULE. The SUBTHALAMIC NUCLEUS and pathways traversing this region are concerned with the integration of somatic motor function.. globus defined as following: A feeling of a lump in the throat that occurs between meals in the absence of other gastrointestinal and motility disorders (e.g., DYSPHAGIA; GASTROESOPHAGEAL REFLUX)..", "label": "yes"}
{"id": "converted_1778", "sentence1": "Is NADPH oxidase 5 expressed in rodents?", "sentence2": "Because the Nox5 gene is absent in rodents, we generated transgenic mice expressing human Nox5 in a podocyte-specific manner (Nox5(pod+)). , The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents. , The data document that the NOX5 gene was expressed in cells of lagomorphs unlike rodents, making the rabbit an interesting model to study NOX5 functions., Nox5 was lost in rodents, and Nox3, which functions in the inner ear in gravity perception, emerged the most recently, corresponding to full-time adaptation of vertebrates to land. , NOX expression patterns in animals are complex and ancestral NOXes, NOX5-like isoforms and DUOXes are generally found. But there are exceptions; for example rodents lack NOX5 and Caenorhabditis elegans expresses only DUOXes., The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents., The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents, NADPH oxidases are the major sources of reactive oxygen species in cardiovascular, neural, and kidney cells. The NADPH oxidase 5 (NOX5) gene is present in humans but not rodents., But there are exceptions; for example rodents lack NOX5 and Caenorhabditis elegans expresses only DUOXes., Because the Nox5 gene is absent in rodents, we generated transgenic mice expressing human Nox5 in a podocyte-specific manner (Nox5(pod+))., The data document that the NOX5 gene was expressed in cells of lagomorphs unlike rodents, making the rabbit an interesting model to study NOX5 functions., The most recently identified member of the Nox family, Nox5, has for the most part been overlooked in renal disease, partly owing to its absence from the rodent genome.[SEP]Relations: NADPH oxidase complex has relations: cellcomp_protein with NOX4, cellcomp_protein with NOX4, cellcomp_protein with NOX3, cellcomp_protein with NOX3, cellcomp_protein with NOXA1, cellcomp_protein with NOXA1, cellcomp_protein with NOX1, cellcomp_protein with NOX1, cellcomp_protein with CYBA, cellcomp_protein with CYBA. Definitions: NADPH oxidases defined as following: A family of membrane-associated flavoprotein NADPH-dependent oxidoreductases that catalyze the univalent reduction of OXYGEN to create SUPEROXIDES. Structurally, they are characterized by six N-terminal transmembrane ALPHA-HELICES, a FLAVIN-ADENINE DINUCLEOTIDE (FAD)-binding region, and a C-terminal NADPH-binding region. They are expressed primarily by EPITHELIAL CELLS in gut, kidney, colon, and smooth muscle tissues, as well as GRANULOCYTES and function to transfer electrons across membranes to molecular oxygen. Defects in the production of superoxide ions by some NADPH oxidases result in GRANULOMATOUS DISEASE, CHRONIC.. rodents defined as following: A mammalian order which consists of 29 families and many genera.. reactive oxygen species 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.. humans defined as following: Members of the species Homo sapiens.. kidney cells defined as following: any of the cells comprising the kidney, functioning in filtering the blood.. renal disease defined as following: Pathological processes of the KIDNEY or its component tissues.. lagomorphs defined as following: An order of small mammals comprising two families, Ochotonidae (pikas) and Leporidae (RABBITS and HARES). Head and body length ranges from about 125 mm to 750 mm. Hares and rabbits have a short tail, and the pikas lack a tail. Rabbits are born furless and with both eyes and ears closed. HARES are born fully haired with eyes and ears open. All are vegetarians. (From Nowak, Walker's Mammals of the World, 5th ed, p539-41). neural defined as following: Of or relating to neurons or the nervous system.. 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.. Caenorhabditis elegans defined as following: A species of nematode that is widely used in biological, biochemical, and genetic studies.. transgenic mice defined as following: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.. vertebrates defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes..", "label": "no"}
{"id": "converted_3931", "sentence1": "Is cadherin a plasma membrane marker?", "sentence2": "the plasma membrane-bound E-cadherin protein, VE-cadherin protein levels were also increased in the plasma membrane fraction. , recycling of VE-cadherin to the plasma membrane,, E-cadherin, a central component of the adherens junction (AJ), is a single-pass transmembrane protein [SEP]Relations: plasma membrane has relations: cellcomp_protein with CADM3, cellcomp_protein with CADM3, cellcomp_protein with CADM2, cellcomp_protein with CADM2, cellcomp_protein with CADM1, cellcomp_protein with CADM1, cellcomp_protein with FURIN, cellcomp_protein with FURIN, cellcomp_protein with ACIN1, cellcomp_protein with ACIN1. Definitions: plasma membrane defined as following: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.. adherens junction defined as following: A cell-cell adherens junction which forms a continuous belt near the apex of epithelial cells. [ISBN:0815316208]. cadherin defined as following: This gene plays a role in cell-cell adhesion and loss of function contributes to the progression of many carcinomas..", "label": "yes"}
{"id": "converted_1544", "sentence1": "Could Hyperthermic intraperitoneal chemotherapy (HIPEC) be effective for the treatment of recurrent ovarian cancer?", "sentence2": "The use of HIPEC after aggressive cytoreductive surgery in patients with ovarian cancer with peritoneal dissemination can be performed with acceptable postoperative morbidity rates. Knowledge of the factors associated with the onset of these postoperative adverse events allows better management of the same and offers the patient a safe procedure, These results showed that the association of HIPEC with a complete cytoreduction for recurrent ovarian cancer presents acceptable morbidity and survival, There is level-one evidence suggesting the benefit of postoperative adjuvant intraperitoneal chemotherapy for patients with advanced ovarian cancer after cytoreductive surgery, albeit catheter-related complications resulted after treatment discontinuation. Studies report the use of HIPEC predominantly in the setting of recurrent disease and have demonstrated encouraging results, which merits further investigation in future clinical trials, The combination of SCR and HIPEC seems to improve survival rate in patients suffering from platinum-sensitive EOC recurrence with respect to no-HIPEC treatments. This result further supports the need of a randomized trial, Cautious extrapolation of data from standard normothermic, nonintraoperative, intraperitoneal chemotherapy and data from Phase II and nonrandomized comparative studies suggest that HIPEC delivered at the time of surgery for ovarian cancer has definite potential, The available evidence suggests that a potential survival benefit of adding HIPEC may be largest in the settings of secondary CRS for stage III ovarian cancer and salvage CRS for recurrent ovarian cancer, two time-points representing failure of initial standard therapy. There is much less evidence for a potential benefit of HIPEC for less advanced stages (I-II) and for earlier time-points in the treatment of ovarian cancer (upfront, interval and consolidation), Survival benefit of adding Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at the different time-points of treatment of ovarian cancer, Patients suffering from peritoneal recurrence of ovarian cancer should be considered for radical reoperation with HIPEC in a center with expertise in multimodal therapeutic options. Organ-preserving cytoreductive surgery allows complete cytoreduction with the goal of decreasing morbidity, In recurrent platinum-sensitive ovarian cancer patients, the use of CRS plus HIPEC represents a safe treatment, able to significantly influence the survival rates compared to chemotherapy alone or surgery plus standard chemotherapy, The results of our study indicate the feasibility and the potential benefit of a protocol including systemic chemotherapy, surgical cytoreduction and HIPEC in patients with peritoneal carcinomatosis from ovarian cancer. A phase III trial to compare this approach with conventional treatment is needed, In selected patients with heavily pretreated recurrent ovarian cancer, cytoreduction combined with HIPEC may provide a meaningful OS with acceptable morbidity. Optimal results are achieved in patients with a macroscopically complete resection and biologically favorable disease, HIPEC is a complement to radical surgery/ peritonectomy, which has been shown to be a surgical procedure with high tolerability, low morbimortality, enhanced survival and prolonged disease-free interval in patients with peritoneal carcinomatosis for recurrent ovarian cancer, Despite the heterogeneity of the studies reviewed, current evidence suggest that complete CRS and HIPEC may be a feasible option with potential benefits that are comparable with the current standard of care. A randomized trial is required to establish the role of HIPEC in ovarian cancer, in the majority of patients with primary and recurrent advanced ovarian cancer, cytoreductive surgery combined with HIPEC can lead to a substantial increase in subsequent rates of disease-free and overall survival, Peritonectomy procedures combined with HIPEC offer promising long-term survival in patients with diffuse peritoneal ovarian carcinomatosis. They achieve high adequate primary and secondary surgical cytoreduction rates with acceptable morbidity and mortality, Cytoreduction surgery with hyperthermic intraperitoneal chemotherapy in recurrent ovarian cancer improves progression-free survival, especially in BRCA-positive patients- a case-control study., Survival benefit of adding Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at the different time-points of treatment of ovarian cancer: review of evidence., Some encouraging results have been reported by the treatment of peritoneal carcinomatosis (PC) from ovarian cancer by complete surgical cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC)., Although standard treatment for advanced epithelial ovarian cancer (EOC) consists of surgical debulking and intravenous platinum- and taxane-based chemotherapy, favorable oncological outcomes have been recently reported with the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)., Trabectedin, Hyperthermic intraperitoneal chemotherapy (HIPEC) and chemo-immunotherapy may be become a promising therapy for the treatment of ovarian cancer., Hyperthermic intraperitoneal chemotherapy (HIPEC) represents a new treatment strategy aimed to improve outcome of patients with advanced ovarian cancer., Favorable oncological outcomes have been reported in several trials with the introduction of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the treatment of Advanced Epithelial Ovarian Cancer (EOC)., Based on theoretical and experimental basis, HIPEC should stand as an effective treatment for ovarian cancer., Some encouraging results have been reported by the treatment of peritoneal carcinomatosis (PC) from ovarian cancer by complete surgical cytoreduction, peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC), Based on theoretical and experimental basis, HIPEC should stand as an effective treatment for ovarian cancer, Hyperthermic intraperitoneal chemotherapy (HIPEC) represents a new treatment strategy aimed to improve outcome of patients with advanced ovarian cancer, [Importance of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer].[SEP]Relations: ovarian epithelial tumor has relations: disease_disease with ovarian squamous cell neoplasm, disease_disease with ovarian squamous cell neoplasm, disease_disease with ovarian neoplasm, disease_disease with ovarian neoplasm, disease_disease with ovarian serous tumor, disease_disease with ovarian serous tumor, disease_disease with epithelial neoplasm, disease_disease with epithelial neoplasm, disease_disease with ovarian seromucinous tumor, disease_disease with ovarian seromucinous tumor. Definitions: Trabectedin defined as following: A tetrahydroisoquinoline alkaloid isolated from the marine tunicate Ecteinascidia turbinata with potential antineoplastic activity. Binding to the minor groove of DNA, trabectedin interferes with the transcription-coupled nucleotide excision repair machinery to induce lethal DNA strand breaks and blocks the cell cycle in the G2 phase.. HIPEC defined as following: A procedure performed in combination with abdominal surgery for cancer that has spread to the abdomen. It involves the infusion of a heated chemotherapy solution that circulates into the abdominal cavity.. ovarian cancer defined as following: A primary or metastatic malignant neoplasm involving the ovary. Most primary malignant ovarian neoplasms are either carcinomas (serous, mucinous, or endometrioid adenocarcinomas) or malignant germ cell tumors. Metastatic malignant neoplasms to the ovary include carcinomas, lymphomas, and melanomas.. CRS defined as following: Transplacental infection of the fetus with rubella usually in the first trimester of pregnancy, as a consequence of maternal infection, resulting in various developmental abnormalities in the newborn infant. They include cardiac and ocular lesions, deafness, microcephaly, mental retardation, and generalized growth retardation. (From Dorland, 27th ed). SCR defined as following: The confirmed disappearance of all signs of cancer, and absence of molecular or cytogenetic marker of disease, in response to treatment with additional biochemical, immunological and histopathological analyses to verify the CR.. platinum-sensitive ovarian cancer defined as following: Ovarian carcinoma that has a documented response to platinum-based chemotherapy.. 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..", "label": "yes"}
{"id": "converted_2843", "sentence1": "Is ADP-ribosylation a PTM?", "sentence2": "ADP-ribosylation is a PTM, in which ADP-ribosyltransferases use nicotinamide adenine dinucleotide (NAD+) to modify target proteins with ADP-ribose, Poly-ADP-ribosylation (PARylation) is a protein posttranslational modification (PTM) that is critically involved in many biological processes that are linked to cell stress responses., ADP-ribosylation is a post-translational modification (PTM) implicated in several crucial cellular processes, ranging from regulation of DNA repair and chromatin structure to cell metabolism and stress responses.[SEP]Relations: DNA ADP-ribosylation has relations: bioprocess_protein with PARP2, bioprocess_protein with PARP2, bioprocess_protein with PARP1, bioprocess_protein with PARP1, bioprocess_protein with PARP3, bioprocess_protein with PARP3, bioprocess_bioprocess with DNA modification, bioprocess_bioprocess with DNA modification. regulation of protein ADP-ribosylation has relations: bioprocess_protein with ADNP, bioprocess_protein with ADNP. Definitions: ADP-ribosyltransferases defined as following: This gene is involved in cellular repair and apoptosis.. nicotinamide adenine dinucleotide defined as following: A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed). ADP-ribose defined as following: An ester formed between the aldehydic carbon of RIBOSE and the terminal phosphate of ADENOSINE DIPHOSPHATE. It is produced by the hydrolysis of nicotinamide-adenine dinucleotide (NAD) by a variety of enzymes, some of which transfer an ADP-ribosyl group to target proteins.. protein posttranslational modification defined as following: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.. Poly-ADP-ribosylation defined as following: The transfer of multiple ADP-ribose molecules to amino acids within target proteins.. ADP-ribosylation defined as following: The transfer of ADP-ribose to amino acids within proteins or to the amino group at N2 of a 2'-deoxyguanosine residue in double-stranded DNA..", "label": "yes"}
{"id": "converted_2215", "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: 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]. yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. DNA defined as following: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).. 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.. HAT 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.. H4 defined as following: This gene plays a role in mitogenesis and differentiation.. 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.. 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). chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. 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]. modification defined as following: Respond with exceptions, completions and modifications or revisions done before completion
. organisms defined as following: A living entity.. nucleus defined as following: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). 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.. 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)..", "label": "no"}
{"id": "converted_1871", "sentence1": "Can NEECHAM Confusion Scale be used for evaluation of postoperative delirium?", "sentence2": "Sampling was achieved in a nonrandomized targeted manner and delirium was assessed using NeeCham questionnaire. , Delirium in older patients: a diagnostic study of NEECHAM Confusion Scale in surgical intensive care unit., AIMS AND OBJECTIVES: To estimate the diagnostic value and determine the feasibility of the NEECHAM Confusion Scale on critically ill older patients., CONCLUSIONS: Findings from this study confirm the good diagnostic value and ease of application of the NEECHAM scale with nonventilated intensive care patients.RELEVANCE TO CLINICAL PRACTICE: The NEECHAM scale can be used to detect delirium during the routine nursing assessment of nonintubated older patients as it requires minimal demand and stress on the patient as well as on the bedside nurse., The NEECHAM Confusion Scale and the validated chart review instrument were used for diagnosis of delirium. , Among the various screening instruments, NEECHAM confusion scale and delirium observation scale appear to be most suitable screening instrument for patients' in general medical and surgical wards, depending on the type of rater (physician or nurse). , Use of NEECHAM scaling enabled medical staff to identify cases of possible confusion early, indicating that the NEECHAM confusion scale should be useful for the detection of postoperative delirium and confusion in the surgical ward., Early detection of postoperative delirium and confusion in a surgical ward using the NEECHAM confusion scale., In this study, we investigated whether the early detection of postoperative delirium in elderly patients is possible using a simple, useful behavior-assessing scale, the NEECHAM Confusion Scale, and a method for comprehensively evaluating elderly persons' stress related to surgery, E-PASS., Assessment of the risk of postoperative delirium in elderly patients using E-PASS and the NEECHAM Confusion Scale., The aim of this study was to determine which of the two delirium observation screening scales, the NEECHAM Confusion Scale or the Delirium Observation Screening (DOS) scale, has the best discriminative capacity for diagnosing delirium and which is more practical for daily use by nurses., For delirium diagnosis and severity assessment, we used the NEECHAM Confusion Scale., Use of NEECHAM scaling enabled medical staff to identify cases of possible confusion early, indicating that the NEECHAM confusion scale should be useful for the detection of postoperative delirium and confusion in the surgical ward., The NEECHAM Confusion Scale was performed upon admission and prior to discharge.RESULTS: The incidence of DSM-IV related delirium was 24%., A comparison of the CAM-ICU and the NEECHAM Confusion Scale in intensive care delirium assessment: an observational study in non-intubated patients., Predictive value and validation of the NEECHAM Confusion Scale using DSM-IV criteria for delirium as gold standard., Early detection of postoperative delirium and confusion in a surgical ward using the NEECHAM confusion scale, The aim of this study was to determine which of the two delirium observation screening scales, the NEECHAM Confusion Scale or the Delirium Observation Screening (DOS) scale, has the best discriminative capacity for diagnosing delirium and which is more practical for daily use by nurses.The project was conducted on four wards of a university hospital; 87 patients were included, In addition, we scored the participants on the NEECHAM Scale and evaluated their postoperative delirium and postoperative arrhythmia.On the nights of Days 4 and 5, the amount of activity of the exposure group was significantly lower and The sympathetic nervous index was significantly lower on the night of Day 5, In this study, we investigated whether the early detection of postoperative delirium in elderly patients is possible using a simple, useful behavior-assessing scale, the NEECHAM Confusion Scale, and a method for comprehensively evaluating elderly persons' stress related to surgery, E-PASS. , The cut-off value of the NEECHAM score was established as 20 points, and patients showing values less than this after surgery were regarded as having postoperative delirium. , Identification of delirium was based on evaluation of the level of consciousness with the NEECHAM Confusion Scale and/or a chart-based instrument for delirium., For delirium diagnosis and severity assessment, we used the NEECHAM Confusion Scale., In this study, we investigated whether the early detection of postoperative delirium in elderly patients is possible using a simple, useful behavior-assessing scale, the NEECHAM Confusion Scale, and a method for comprehensively evaluating elderly persons' stress related to surgery, E-PASS.The subjects were 160 patients aged more than 75 years who underwent surgery., In this study a nursing screening instrument, the NEECHAM confusion scale, was studied for early recognition of delirium ICU patients., The psychometric characteristics and the ease of use of the NEECHAM confusion scale enables ICU nurses to early recognize delirium., The trends of the NEECHAM scores in the 3 groups were compared, and the relationship between the NEECHAM scores and suspected clinical risk factors for delirium was investigated., In groups showing an MMSE score of less than 25 or a preoperative NEECHAM score of less than 27, the incidence of postoperative delirium was 76%.CONCLUSION: The results suggest that E-PASS and the NEECHAM score facilitate assessment of the risk of postoperative delirium in elderly patients, contributing to early prevention/treatment., In this study, we investigated whether the early detection of postoperative delirium in elderly patients is possible using a simple, useful behavior-assessing scale, the NEECHAM Confusion Scale, and a method for comprehensively evaluating elderly persons' stress related to surgery, E-PASS., Use of NEECHAM scaling enabled medical staff to identify cases of possible confusion early, indicating that the NEECHAM confusion scale should be useful for the detection of postoperative delirium and confusion in the surgical ward.., Early detection of postoperative delirium and confusion in a surgical ward using the NEECHAM confusion scale., Assessment of the risk of postoperative delirium in elderly patients using E-PASS and the NEECHAM Confusion Scale., For delirium diagnosis and severity assessment, we used the NEECHAM Confusion Scale., The Neecham Confusion Scale and the Delirium Observation Screening Scale: capacity to discriminate and ease of use in clinical practice., The aim of this study was to determine which of the two delirium observation screening scales, the NEECHAM Confusion Scale or the Delirium Observation Screening (DOS) scale, has the best discriminative capacity for diagnosing delirium and which is more practical for daily use by nurses.[SEP]Relations: delirium has relations: contraindication with Trolnitrate, contraindication with Trolnitrate, disease_disease with cognitive disorder, disease_disease with cognitive disorder, disease_disease with subacute delirium, disease_disease with subacute delirium, contraindication with Tacrolimus, contraindication with Tacrolimus, contraindication with Olanzapine, contraindication with Olanzapine. Definitions: delirium defined as following: A disorder characterized by CONFUSION; inattentiveness; disorientation; ILLUSIONS; HALLUCINATIONS; agitation; and in some instances autonomic nervous system overactivity. It may result from toxic/metabolic conditions or structural brain lesions. (From Adams et al., Principles of Neurology, 6th ed, pp411-2). postoperative delirium defined as following: A form of DELIRIUM which occurs after GENERAL ANESTHESIA.. critically ill defined as following: A disease or state in which death is possible or imminent..", "label": "yes"}
{"id": "converted_2096", "sentence1": "Is Cryptococcus neoformans a frequent cause of isolated skin infections in immunocompromised individuals", "sentence2": " Cryptococcus is an opportunistic yeast with a worldwide distribution that primarily causes significant infections in immunocompromised individuals, generally by affecting the respiratory tract. But primary cutaneous cryptococcosis (PCC) without systemic infection is rare. , Cryptococcus is a ubiquitous fungus and is known for causing meningitis and cutaneous infections in immunocompromised individuals., Cryptococcus neoformans is an encapsulated yeast that can cause primary pulmonary infections or disseminate and cause infections of the central nervous system, meninges, skin, and bone in the immunocompromised host., The authors report a male patient, a seller with no detected immunosuppression, with an extensive ulcerated skin lesion localized on the left forearm, caused by Cryptococcus neoformans var.[SEP]Relations: Recurrent skin infections has relations: phenotype_phenotype with Recurrent bacterial skin infections, phenotype_phenotype with Recurrent bacterial skin infections, phenotype_phenotype with Recurrent viral skin infections, phenotype_phenotype with Recurrent viral skin infections, phenotype_phenotype with Recurrent cutaneous fungal infections, phenotype_phenotype with Recurrent cutaneous fungal infections, disease_phenotype_positive with immunodeficiency, disease_phenotype_positive with immunodeficiency, disease_phenotype_positive with acquired ichthyosis, disease_phenotype_positive with acquired ichthyosis. Definitions: yeast defined as following: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as \"baker's\" or \"brewer's\" yeast. The dried form is used as a dietary supplement.. Cryptococcus neoformans defined as following: An acute or chronic, localized or disseminated infection by Cryptococcus neoformans. Sites of involvement include the lungs, central nervous system and meninges, skin, and visceral organs.--2004. systemic infection defined as following: Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.. 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). meninges defined as following: The three membranes that cover the BRAIN and the SPINAL CORD. They are the dura mater, the arachnoid, and the pia mater.. cutaneous infections defined as following: Infections of the skin that happen multiple times. [HPO:curators]. skin infections defined as following: Skin diseases caused by bacteria, fungi, parasites, or viruses..", "label": "no"}
{"id": "converted_1408", "sentence1": "Could Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) cause sudden cardiac death?", "sentence2": "Here we refine our approach, and apply it to novel variants found in 2266 patients across two large cohorts with inherited sudden death syndromes, namely catecholaminergic polymorphic ventricular tachycardia (CPVT) or Brugada syndrome (BrS)., Calsequestrin-associated catecholaminergic polymorphic ventricular tachycardia (CPVT2) can cause sudden death in young individuals in response to stress. , Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. The arrhythmias may cause syncope or degenerate into cardiac arrest and sudden death which usually occurs during childhood, In many cases the cause of death can be elucidated by medico-legal autopsy, however, a significant number of these cases remain unexplained despite a detailed postmortem investigation and are labeled as sudden unexplained death (SUD). Post-mortem genetic testing, so called molecular autopsy, revealed that primary arrhythmogenic disorders including long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT) may account for a certain number of these cases., We report a family with repeat events of sudden cardiac death and recurrent ventricular fibrillation in a teenage girl, where autopsy data and clinical investigations were inconclusive. The diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) was established only following finding a gene mutation in the cardiac ryano, Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating inherited disorder characterized by episodic syncope and/or sudden cardiac arrest during exercise or acute emotion in individuals without structural cardiac abnormalities. Although rare, CPVT is suspected to cause a substantial part of sudden cardiac deaths in young individuals. , In conclusion, patients with CASQ2-associated CPVT should be recommended to receive ICDs to prevent sudden death when medical therapy is not effective., Cardiac channelopathies associated with structurally normal hearts such as long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS) yield no evidence to be found at autopsy, leaving coroners, medical examiners, and forensic pathologists only to speculate that a lethal arrhythmia might lie at the heart of a sudden unexplained death (SUD)., Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare adrenergically mediated arrhythmogenic disorder classically induced by exercise or emotional stress and found in structurally normal hearts. It is an important cause of cardiac syncope and sudden death in childhood., We also compare CPVT to other notable cardiomyopathic and channelopathic causes of sudden death in youth including hypertrophic cardiomyopathy, arrhythmogenic right ventricular dysplasia, long QT syndrome, short QT syndrome, and Brugada syndrome., Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease that can cause sudden cardiac death due to ventricular fibrillation (VF)., Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease that manifests as syncope or sudden death during high adrenergic tone in the absence of structural heart defects., Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a cardiac channelopathy characterized by altered intracellular calcium handling resulting in ventricular arrhythmias and high risk of cardiac sudden death in young cases with normal structural hearts, Early detection of CPVT is crucial because opportune medical intervention prevents sudden cardiac death. , If untreated, CPVT is highly lethal, as approximately 30% of affected individuals experience at least one cardiac arrest and up to 80% one or more syncopal spells. Sudden death may be the first manifestation of the disease. , Hereditary non-structural diseases such as catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT, and the Brugada syndrome as well as structural disease such as hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) cause a significant percentage of sudden cardiac deaths in the young, Patients with CPVT present with exercise-induced syncope and sudden cardiac death but normal resting electrocardiograms., Although structural cardiovascular abnormalities explain most cases of sudden cardiac death in young people, the cause of death remains unexplained after autopsy in 10% to 30% of cases. Potentially lethal ion channel disorders (channelopathies) such as the long QT syndromes (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and the Brugada syndrome (BrS) may account for at least one-third of these unexplained cases. , Based on these data, we propose that CPVT is a combined neurocardiac disorder in which leaky RyR2 channels in the brain cause epilepsy, and the same leaky channels in the heart cause exercise-induced sudden cardiac death., The inherited arrhythmogenic diseases associated with the transmembranous ionic channels, anchoring proteins or intracellular calcium regulating proteins are thought to be responsible for sudden cardiac death in infants, children, and young adults who have structurally normal hearts. Recent genetic analyses have identified congenital diseases such as the long-QT syndrome (LQTS), the Jervell and Lange-Nielsen syndrome (JLNS), the Brugada syndrome (BrS), the short-QT syndrome (SQTS), the arrhythmogenic right ventricular cardiomyopathy type 2 (ARVC2), and the catecholamine-induced polymorphic ventricular tachycardia (CPVT) /familial polymorphic ventricular tachycardia (FPVT). , At least some cases of sudden, unexplained death in young individuals may be ascribed to CPVT[SEP]Relations: catecholaminergic polymorphic ventricular tachycardia has relations: disease_phenotype_positive with Sudden cardiac death, disease_phenotype_positive with Sudden cardiac death, disease_phenotype_positive with Sudden death, disease_phenotype_positive with Sudden death, disease_phenotype_positive with Cardiac arrest, disease_phenotype_positive with Cardiac arrest. Sudden cardiac death has relations: disease_phenotype_positive with catecholaminergic polymorphic ventricular tachycardia, disease_phenotype_positive with catecholaminergic polymorphic ventricular tachycardia. Sudden death has relations: disease_phenotype_positive with catecholaminergic polymorphic ventricular tachycardia, disease_phenotype_positive with catecholaminergic polymorphic ventricular tachycardia. Definitions: BrS defined as following: A scale developed by Smith, et al, designed to assess an individual's ability to recover from stressful circumstances.. cardiac abnormalities defined as following: Developmental abnormalities involving structures of the heart. These defects are present at birth but may be discovered later in life.. CPVT2 defined as following: An autosomal recessive condition caused by mutation(s) in the CASQ2 gene, encoding calsequestrin-2. It is characterized by a relative resting bradycardia and a slight prolongation of the QTc interval. Polymorphic ventricular tachycardia may be induced with exercise stress testing or isoproterenol infusion.. arrhythmia defined as following: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.. 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). ICDs defined as following: Implantable devices which continuously monitor the electrical activity of the heart and automatically detect and terminate ventricular tachycardia (TACHYCARDIA, VENTRICULAR) and VENTRICULAR FIBRILLATION. They consist of an impulse generator, batteries, and electrodes.. 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.. cardiac arrest defined as following: Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.. 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.. HCM defined as following: A form of CARDIAC MUSCLE disease, characterized by left and/or right ventricular hypertrophy (HYPERTROPHY, LEFT VENTRICULAR; HYPERTROPHY, RIGHT VENTRICULAR), frequent asymmetrical involvement of the HEART SEPTUM, and normal or reduced left ventricular volume. Risk factors include HYPERTENSION; AORTIC STENOSIS; and gene MUTATION; (FAMILIAL HYPERTROPHIC CARDIOMYOPATHY).. 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). polymorphic defined as following: The quality or state of being able to assume different forms.. SQTS defined as following: Ventricular tachyarrhythmias occurring in association with short QT syndrome.. congenital diseases defined as following: existing at, and usually before, birth; referring to conditions that are present at birth, regardless of their causation; inborn metabolism disorders are generally not treed here.. arrhythmogenic right ventricular cardiomyopathy defined as following: A congenital cardiomyopathy that is characterized by infiltration of adipose and fibrous tissue into the RIGHT VENTRICLE wall and loss of myocardial cells. Primary injuries usually are at the free wall of right ventricular and right atria resulting in ventricular and supraventricular arrhythmias.. cardiovascular abnormalities defined as following: Congenital, inherited, or acquired anomalies of the CARDIOVASCULAR SYSTEM, including the HEART and BLOOD VESSELS.. calcium defined as following: A dietary supplement containing the mineral calcium.. long QT syndrome defined as following: A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.. 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). ventricular fibrillation defined as following: An electrocardiographic finding of a rapid grossly irregular ventricular rhythm with marked variability in QRS cycle length, morphology, and amplitude. The rate is typically greater than 300 bpm. (CDISC). 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.. sudden cardiac arrest defined as following: Sudden suspension of cardiac activity that is usually due to ARRHYTHMIA, in contrast to heart attack (MYOCARDIAL INFARCTION) which occurs due to blockage. The sudden suspension of cardiac activity generally requires RESUSCITATION.. variants defined as following: An alteration or difference from a norm or standard.. gene mutation defined as following: A change in the nucleotide sequence of the TAF1 gene.. cardiac channelopathy defined as following: A disorder that affects the myocardial ion channels, altering the electrical properties of the heart and changing the ECG and/or predisposing the subject to pro-arrhythmic events.. channelopathies defined as following: A variety of neuromuscular conditions resulting from MUTATIONS in ION CHANNELS manifesting as episodes of EPILEPSY; HEADACHE DISORDERS; and DYSKINESIAS.. LQTS defined as following: A rare group of genetic, cardiac rhythm diseases characterized by a prolongation of the QT interval at basal electrocardiography (ECG) and by a high risk of life-threatening arrhythmias.. CPVT defined as following: An electrocardiographic finding of ventricular tachycardia that is associated with syncope and/or cardiac arrest triggered by emotion or exercise in patients whose baseline ECG is normal. (ACC). Lange-Nielsen syndrome defined as following: A form of long QT syndrome that is associated with congenital deafness. It is characterized by abnormal cardioelectrophysiology involving the VOLTAGE-GATED POTASSIUM CHANNEL. It results from mutation of KCNQ1 gene (Subtype 1 or JLN1) or the KCNE1 gene (Subtype 2 or JLN2).. 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).", "label": "yes"}
{"id": "converted_509", "sentence1": "Is phospholamban a regulatory/inhibitory protein of the Ca ATPase SERCA?", "sentence2": "The membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes, thereby modulating cardiac contractility. β-Adrenergic-stimulated phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown mechanism., Phospholamban (PLN) is a type II membrane protein that inhibits the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), thereby regulating calcium homeostasis in cardiac muscle. In membranes, PLN forms pentamers that have been proposed to function either as a storage for active monomers or as ion channels., Regulation of the SERCA calcium pump by phospholamban (PLB) is largely due to interactions between their respective transmembrane domains. In spite of numerous mutagenesis and kinetic studies, we still do not have a clear mechanistic picture of how PLB influences the calcium transport cycle of SERCA., Calcium transport across the membrane of the sarcoplasmic reticulum (SR) plays an important role in the regulation of heart muscle contraction and relaxation. The sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA) 2a is responsible for Ca(2+) up-take by this organelle and is inhibited in a reversible manner by phospholamban, another SR membrane protein. Thus, alleviation of phospholamban-mediated inhibition of SERCA2a is a potential therapeutic option for heart failure and cardiomyopathy., Phospholamban has been suggested to be a key regulator of cardiac sarcoplasmic reticulum (SR) Ca cycling and contractility and a potential therapeutic target in restoring the depressed Ca cycling in failing hearts., In larger mammals, a higher fraction of SERCA2a pumps are regulated by phospholamban, and this may influence therapeutic strategies to enhance cardiac contractility and functional cardiac reserve., Phospholamban (PLB) inhibits the sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA), and this inhibition is relieved by Ca(2+) calmodulin-dependent protein kinase II (CaM kinase II) phosphorylation, These findings suggest that PLB is an important modulator of gastric antrum smooth muscle contractility by modulation of SR Ca(2+) release and CaM kinase II activity., The function of the SERCA pump is modulated by the endogenous molecules phospholamban (PLB) and sarcolipin (SLN), expressed in cardiac and skeletal muscles. The mechanism of action of PLB on SERCA is well characterized, whereas that of SLN is only beginning to be understood. , Phospholamban (PLB) is an inhibitor of the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA)., These results show that alteration of the PLB:SERCA ratio can significantly modulate smooth muscle [Ca2+]i., Phospholamban expressed in cardiac muscle and sarcolipin expressed in skeletal muscle regulate SERCA activity., Phospholamban (PLB) is a 24- to 27-kDa phosphoprotein that modulates activity of the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA). Expression of PLB is reportedly limited to cardiac, slow-twitch skeletal and smooth muscle in which PLB is an important regulator of [Ca2+]i and contractility in these muscles., Regulation of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA 2a) depends on the phosphorylation state of phospholamban (PLB). When PLB is phosphorylated, its inhibitory effect towards SERCA 2a is relieved, leading to an enhanced myocardial performance. , Ca(2+) reuptake occurs via sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA) and is regulated by the inhibitory protein phospholamban (PLB) in many cell types., Phospholamban (PLN) is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (SERCA) in the sarcoplasmic reticulum., Phospholamban (PLN) is the endogenous inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), the integral membrane enzyme responsible for 70�% of the removal of Ca(2+) from the cytosol, inducing cardiac muscle relaxation in humans., Phospholamban (PLB) is an integral membrane protein regulating Ca(2+) transport through inhibitory interaction with sarco(endo)plasmic reticulum calcium ATPase (SERCA)., Phosphorylation by protein kinase A and dephosphorylation by protein phosphatase 1 modulate the inhibitory activity of phospholamban (PLN), the endogenous regulator of the sarco(endo)plasmic reticulum calcium Ca(2+) ATPase (SERCA)., Phosphorylation by protein kinase A and dephosphorylation by protein phosphatase 1 modulate the inhibitory activity of phospholamban (PLN), the endogenous regulator of the sarco(endo)plasmic reticulum calcium Ca(2+) ATPase (SERCA), We used EPR spectroscopy to probe directly the interaction between phospholamban (PLB) and its regulatory target, the sarcoplasmic reticulum Ca-ATPase (SERCA)[SEP]Relations: phosphoprotein phosphatase activity has relations: molfunc_protein with PPP2CA, molfunc_protein with PPP2CA, molfunc_protein with PPP1CA, molfunc_protein with PPP1CA, molfunc_protein with PTEN, molfunc_protein with PTEN, molfunc_protein with PPP5C, molfunc_protein with PPP5C. membrane has relations: cellcomp_protein with CACNB3, cellcomp_protein with CACNB3. Definitions: Phospholamban defined as following: free sarcoplasmic reticulum polymeric proteolipid which modulates sarcoplasmic reticulum function; phosphorylated by cAMP-dependent, calcium-calmodulin-dependent, and calcium-phospholipid-dependent protein kinases.. organelle defined as following: Cell part which consists of macromolecules aggregated into discrete structures in the protoplasm. (Digital Anatomist Foundational Model). cardiomyocytes defined as following: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).. mutagenesis defined as following: Production of genetic alterations by any technique, including chemicals, radiation, recombination, or other molecular biology methods.. CaM kinase II defined as following: A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.. heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. skeletal muscles defined as following: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.. 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).. protein kinase A 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.. smooth muscle defined as following: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed). 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.. membrane protein 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.. membranes defined as following: Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures.. muscles defined as following: Contractile tissue that produces movement in animals.. SR defined as following: Human SNCG wild-type allele is located within10q23.2-q23.3 and is approximately 13 kb in length. This allele, which encodes gamma-synuclein protein, plays a role in the modulation of axonal architecture and neurofilament integrity. This gene is highly expessed in advanced breast carcinomas, suggesting a correlation between SNCG overexpression and breast tumor development.. sarcoplasmic reticulum Ca(2+)-ATPase defined as following: Calcium-transporting ATPases that catalyze the active transport of CALCIUM into the SARCOPLASMIC RETICULUM vesicles from the CYTOPLASM. They are primarily found in MUSCLE CELLS and play a role in the relaxation of MUSCLES.. protein phosphatase 1 defined as following: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992). heart muscle 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.. cytosol defined as following: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.. 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]. mammals defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. humans defined as following: Members of the species Homo sapiens.. membrane defined as following: A device that is made from or resembles a thin flexible sheet of material.. integral membrane defined as following: The component of a 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:go_curators].", "label": "yes"}
{"id": "converted_3362", "sentence1": "Is CTCF bound at nucleosome free regions?", "sentence2": "Nucleosome depletion at 5'-HS4 was dependent on interaction of the insulator protein CCCTC-binding factor (CTCF) and was required for enhancer blocking. , Here, we show that promoter classes are significantly differentiated by nucleosome organization and chromatin structure. Dispersed promoters display higher associations with well-positioned nucleosomes downstream of the TSS and a more clearly defined nucleosome free region upstream, while focused promoters have a less organized nucleosome structure, yet higher presence of RNA polymerase II., hese differences extend to histone variants (H2A.Z) and marks (H3K4 methylation), as well as insulator binding (such as CTCF), independent of the expression levels of affected genes., nucleosome occupancy at nucleosome-free regions (NFRs), many of which are located at sites occupied by the multivalent factors Ctcf and cohesin. , This general architectural change correlates with enhanced binding of CTCF and cohesins and more pronounced insulation of contacts across chromatin boundaries in lineage-committed cells. , robust inter-nucleosomal interactions exist around transcription start site (TSS), transcription termination sites (TTS) or around CTCF binding sites[SEP]Relations: nucleosome has relations: cellcomp_protein with IRF4, cellcomp_protein with IRF4, cellcomp_protein with CENPA, cellcomp_protein with CENPA, cellcomp_protein with H3C15, cellcomp_protein with H3C15, cellcomp_protein with H3C14, cellcomp_protein with H3C14, cellcomp_protein with H4C15, cellcomp_protein with H4C15. Definitions: H2A.Z defined as following: Human H2AZ1 wild-type allele is located in the vicinity of 4q24 and is approximately 2 kb in length. This allele, which encodes histone H2A.Z protein, plays a role in chromatin packaging.. nucleosomes defined as following: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4.. TSS defined as following: A rare acute life-threatening systemic bacterial noncontagious illness caused by any of several related staphylococcal exotoxins. It is characterized by high fever, hypotension, rash, multi-organ dysfunction, and cutaneous desquamation during the early convalescent period. The toxins affect the host immune system, causing an exuberant and pathological host inflammatory response. Laboratory findings include leukocytosis, elevated prothrombin time, hypoalbuminemia, hypocalcemia, and pyuria.. CTCF defined as following: CCN family member 2 (349 aa, ~38kDa) is encoded by the human CCN2 gene. This protein plays a role in the promotion of proliferation and differentiation of chondrocytes and also mediates heparin- and divalent cation-dependent cell adhesion in many different cell types.. 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.. sites defined as following: A position in relation to its surroundings.. transcription start site defined as following: The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.. promoters defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. H3K4 defined as following: The lysine residue found at amino acid position 4 in the histone H3 protein. Methylation of this residue may be a marker for transcriptionally active genes.. enhancer defined as following: A 50-150bp DNA sequence that increases the rate of transcription of coding sequences. It may be located at various distances and in either orientation upstream from, downstream from or within a structural gene. When bound by a specific transcription factor it increases the levels of expression of the gene, but is not sufficient alone to cause expression. Distinguished from a promoter, that is alone sufficient to cause expression of the gene when bound.. binding sites defined as following: The parts of a macromolecule that directly participate in its specific combination with another molecule.. Nucleosome defined as following: A complex comprised of DNA wound around a multisubunit core and associated proteins, which forms the primary packing unit of DNA into higher order structures. [GOC:elh]. genes defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms..", "label": "yes"}
{"id": "converted_2476", "sentence1": "Can canagliflozin cause euglycemic diabetic ketoacidosis?", "sentence2": "CASE REPORT: We present a case of a 57-year-old woman with type 2 diabetes mellitus taking a combination of canagliflozin and metformin who presented with progressive altered mental status over the previous 2 days. Her work-up demonstrated a metabolic acidosis with an anion gap of 38 and a venous serum pH of 7.08. The serum glucose was 168 mg/dL. The urinalysis showed glucose>500 mg/dL and ketones of 80 mg/dL. Further evaluation demonstrated an elevated serum osmolality of 319 mOsm/kg and an acetone concentration of 93 mg/dL. She was treated with intravenous insulin and fluids, and the metabolic abnormalities and her altered mental status resolved within 36 h. This was the first episode of diabetic ketoacidosis (DKA) for this patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Diabetic patients on SGLT2 inhibitor medications are at risk for ketoacidosis. Due to the renal glucose-wasting properties of these drugs, they may present with ketoacidosis with only mild elevations in serum glucose, potentially complicating the diagnosis. , Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin., We herein report the case of a 27-year-old Asian woman with type 2 diabetes who was treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin) who developed euglycemic diabetic ketoacidosis and persistent diuresis in the absence of hyperglycemia., Canagliflozin raised the risk of amputations and the rate of fractures in the CANVAS trial, although more data are necessary before drawing definite conclusions. The risk of euglycemic diabetic ketoacidosis seems to be minimal when the drugs are prescribed properly., Severe Ketoacidosis Associated with Canagliflozin (Invokana): A Safety Concern., However, some serious side effects, including severe anion gap metabolic acidosis and euglycemic diabetic ketoacidosis (DKA), have been reported. , At present, the Food and Drug Administration (FDA) has only approved three medications (canagliflozin, dapagliflozin and empagliflozin) in this drug class for the management of Type 2 diabetes. In May 2015, the FDA issued a warning of ketoacidosis with use of this drug class., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient., Nonconvulsive Status Epilepticus in Elderly Patients Receiving SSRIs; Euglycemic Diabetic Ketoacidosis Associated with Canagliflozin Use in a Type 1 Diabetic Patient; Duloxetine-Induced Galactorrhea; Canagliflozin-Associated Severe Hypercalcemia and Hypernatremia; Vemurafenib-Induced Fanconi Syndrome., Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin., We are reporting a timely case of atypical euglycemic diabetic ketoacidosis in a type 1 diabetic patient treated with sodium-glucose cotransporter-2 (SGLT-2) inhibitor canagliflozin., Euglycemic ketoacidosis did not recur in our patient after discontinuing canagliflozin. , Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin., In this article, we present a case of a 50-year-old woman with type 2 diabetes who developed euglycemic DKA after initiating therapy with canagliflozin. , SGLT2 inhibitors such as canagliflozin may predispose patients not only to diabetic ketoacidosis but also to prolonged glucosuria., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.
, We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient., CONCLUSION Treatment with canagliflozin was associated with development of euglycemic ketoacidosis., Euglycemic Diabetic Ketoacidosis with Persistent Diuresis Treated with Canagliflozin., We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.., Euglycemic Diabetic Ketoacidosis With Prolonged Glucosuria Associated With the Sodium-Glucose Cotransporter-2 Canagliflozin., Euglycemic Diabetic Ketoacidosis in a 27 year-old female patient with type-1-Diabetes treated with sodium-glucose cotransporter-2 (SGLT2) inhibitor Canagliflozin.[SEP]Relations: Canagliflozin has relations: drug_drug with Carbetocin, drug_drug with Carbetocin, drug_drug with Ketobemidone, drug_drug with Ketobemidone. diabetic ketoacidosis has relations: contraindication with Norfloxacin, contraindication with Norfloxacin, contraindication with Inositol, contraindication with Inositol, contraindication with Inositol nicotinate, contraindication with Inositol nicotinate. Definitions: renal defined as following: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.. SSRIs defined as following: Any agent that increases the extracellular level of the neurotransmitter serotonin (5-HT) by inhibiting its reuptake into the presynaptic cell. Increased level in the synaptic cleft prolongs the action of 5-HT on the postsynaptic receptor. This type of agent is typically used as an antidepressant and in the treatment of anxiety disorders and some personality disorders. They are also typically effective and used in treating some cases of insomnia.. metformin defined as following: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289). DKA defined as following: A life-threatening complication of diabetes mellitus, primarily of TYPE 1 DIABETES MELLITUS with severe INSULIN deficiency and extreme HYPERGLYCEMIA. It is characterized by KETOSIS; DEHYDRATION; and depressed consciousness leading to COMA.. ketones defined as following: Organic compounds containing a carbonyl group =C=O bonded to two hydrocarbon groups.. Canagliflozin defined as following: A C-glucoside with a thiophene ring that is an orally available inhibitor of sodium-glucose transporter 2 (SGLT2) with antihyperglycemic activity. Canagliflozin is also able to reduce body weight and has a low risk for hypoglycemia.. ketoacidosis defined as following: Acidosis resulting from accumulation of ketone bodies. [HPO:probinson]. sodium-glucose cotransporter 2 defined as following: The founding member of the sodium glucose transport proteins. It is predominately expressed in the INTESTINAL MUCOSA of the SMALL INTESTINE.. acetone defined as following: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis.. empagliflozin defined as following: An orally available competitive inhibitor of sodium-glucose co-transporter 2 (SGLT2; SLC5A2) with antihyperglycemic activity. Upon oral administration, empagliflozin selectively and potently inhibits SGLT2 in the kidneys, thereby suppressing the reabsorption of glucose in the proximal tubule. Inhibition of SGLT2 increases urinary glucose excretion by the kidneys, resulting in a reduction of plasma glucose levels in an insulin-independent manner. Inhibition of SGLT2 in the kidneys also suppresses the renal reabsorption of 1,5-anhydroglucitol (1,5AG). This lowers serum 1,5AG and neutrophil 1,5-anhydroglucitol-6-phosphate (1,5AG6P) levels, which may improve neutropenia and neutrophil dysfunction in patients with glycogen storage disease type Ib (GSD Ib). SGLT2, a transport protein exclusively expressed in the proximal renal tubules, mediates approximately 90% of renal glucose reabsorption from tubular fluid.. dapagliflozin defined as following: A selective sodium-glucose co-transporter subtype 2 (SGLT2) inhibitor with antihyperglycemic activity. Dapagliflozin selectively and potently inhibits SGLT2 compared to SGLT1, which is the cotransporter of glucose in the gut.. Hypernatremia defined as following: Higher than normal levels of sodium in the circulating blood.. SGLT2 defined as following: Human SLC5A2 wild-type allele is located in the vicinity of 16p11.2 and is approximately 8 kb in length. This allele, which encodes sodium/glucose cotransporter 2 protein, plays a role in sodium-dependent glucose transport. Mutation of the gene is associated with renal glucosuria.. glucosuria defined as following: The appearance of an abnormally large amount of GLUCOSE in the urine, such as more than 500 mg/day in adults. It can be due to HYPERGLYCEMIA or genetic defects in renal reabsorption (RENAL GLYCOSURIA).. woman defined as following: An adult, female human.. Type 2 diabetes defined as following: A type of diabetes mellitus that is characterized by insulin resistance or desensitization and increased blood glucose levels. This is a chronic disease that can develop gradually over the life of a patient and can be linked to both environmental factors and heredity.. Hypercalcemia defined as following: Abnormally high level of calcium in the blood.. amputations defined as following: The surgical removal of part of, or all of, a limb or other appendage or outgrowth of the body.. metabolic acidosis defined as following: Increased acidity in the blood secondary to acid base imbalance. Causes include diabetes, kidney failure and shock.. fractures defined as following: A traumatic injury to the bone in which the continuity of the bone is broken..", "label": "yes"}
{"id": "converted_1941", "sentence1": "Is NSD-1015 an inhibitor of Aromatic L-Amino Acid Decarboxylase?", "sentence2": "When pretreated with a central AADC inhibitor (NSD-1015), further application of l-dopa failed to increase the motoneuron activity although the expression of DA in the AADC cells was not completely inhibited. , Inhibition of Ddc by AADC inhibitor NSD-1015 or anti-sense morpholino oligonucleotides (MO) reduced brain volume and body length. , We evaluated this in vivo by reverse dialysis of the aromatic-l-amino-acid decarboxylase (EC 4.1.1.28) inhibitor NSD-1015 (20μM) and selected concentrations of l- or d-tyrosine. , Neurochemical study of effects of the new anxiolytic drugs afobazol and ladasten on the synthesis and metabolism of monoamines and their metabolites in the brain structures of Wistar rat on the model of monoamine synthesis blockade induced by aromatic amino acid decarboxylase inhibitor NSD-1015, To establish the neurotransmitter role(s) of L-3,4-dihydroxyphenylalanine (DOPA) in its own right, we attempted to clarify whether i.p. injection of a DOPA antagonist, DOPA cyclohexyl ester (CHE), would antagonize the behavioral responses of conscious rats to DOPA in the presence of 3-hydroxybenzylhydrazine (NSD-1015) (100 mg/kg i.p.), a central aromatic L-amino acid decarboxylase (AADC) inhibitor., TH and TPH activities were determined in tissue extracts by measuring the accumulation of L-Dopa and 5-HTP respectively, following the administration of the aromatic L-amino acid decarboxylase inhibitor, NSD-1015. , Results of a neurochemical study of the effects of the new anxiolytic drugs afobazole and ladasten on the synthesis and metabolism of monoamines and their metabolites determined by HPLC on the model of monoamine synthesis blockade induced by NSD-1015 (aromatic L-amino acid decarboxylase) in the brain structures of Wistar rats are reported. , . When pretreated with a central AADC inhibitor (NSD-1015), NSD 1015 (general AADC inhibitor), monoamine synthesis blockade induced by NSD-1015 (aromatic L-amino acid decarboxylase) , the aromatic-l-amino-acid decarboxylase (EC 4.1.1.28) inhibitor NSD-1015, An accumulation of L-dihydroxyphenylalanine (DOPA) in the median eminence of female rats treated with 3-hydroxybenzylhydrazine (NSD 1015), and inhibitor of aromatic L-amino acid decarboxylase (DOPA decarboxylase) activity, was associated with a decreased concentration of dopamine in the median eminence and pronounced reduction in the release of dopamine into hypophysial portal blood., 6S-BH4 increased extracellular DOPA levels in the presence of NSD 1015, an inhibitor of aromatic L-amino acid decarboxylase (an index of in vivo tyrosine hydroxylase activity), to an extent similar to the increase induced by 6R-BH4., 5-HT synthesis was estimated by measuring the accumulation of the 5-HT precursor, 5-hydroxytryptophan (5-HTP), in the neurointermediate lobe of male Long-Evans rats following the administration of NSD 1015, an inhibitor of aromatic L-amino acid decarboxylase., Monoamine synthesis was studied in different parts of the brain by measuring the accumulated dopa and 5-hydroxytryptophan (5-HTP), 30 min after NSD 1015 (3-hydroxybenzylhydrazine HCl, 100 mg/kg) an inhibitor of aromatic L-amino-acid decarboxylase, given i.p., HPLC coupled with electrochemical detection was used to make concurrent measurements of the rate of accumulation of 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine in selected brain regions (striatum, nucleus accumbens, septum, medial periventricular hypothalamus) and thoracic spinal cords of rats treated with NSD 1015, an inhibitor of aromatic-L-amino-acid decarboxylase., The activity of 5-hydroxytryptaminergic neurons has been estimated from measurements of: concentrations of 5-hydroxyindoleacetic acid; the ratio of the concentrations of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine; the rate of accumulation of 5-hydroxytryptophan following the administration of an aromatic L-amino acid decarboxylase inhibitor (e.g., NSD 1015); the rate of accumulation of 5-hydroxytryptamine, and the rate of decline of 5-hydroxyindoleacetic acid following the administration of a monoamine oxidase inhibitor (e.g., pargyline)., The accumulation of dopa (3,4-dihydroxyphenylalanine) after administration of NSD 1015 to inhibit aromatic l-amino acid decarboxylase was determined as an index of NE synthesis., The central aromatic amino acid DOPA decarboxylase inhibitor, NSD-1015, does not inhibit L-DOPA-induced circling in unilateral 6-OHDA-lesioned-rats., The centrally acting aromatic amino acid dopa decarboxylase (AADC) inhibitor, 3-hydroxybenzyl hydrazine (NSD-1015), is widely used to study the neurotransmitter-like actions of L-DOPA., The aromatic amino acid decarboxylase inhibitor, NSD-1015, increases release of dopamine: response characteristics., The aromatic amino acid decarboxylase inhibitor NSD 1015 markedly increased the dopa concentration., Using a microdialysis technique, the rat striatum was perfused with NSD-1015, an inhibitor of aromatic L-amino acid decarboxylase, and the amount of L-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytryptophan (5-HTP) accumulating in dialysate was measured as an index of in vivo activities of tyrosine hydroxylase and tryptophan hydroxylase., Also, we studied the effect of MnCl2 on extracellular levels of l-Dopa in the presence of aromatic amino acid decarboxylase (AADC) inhibitor 3-hydroxybencilhydracine-HCl (NSD 1015)., The role of L-DOPA itself was investigated by administering several doses of an aromatic L-amino acid decarboxylase inhibitor, NSD 1015, prior to 100 mg/kg L-DOPA to 5-day-old rats., An accumulation of L-dihydroxyphenylalanine (DOPA) in the median eminence of female rats treated with 3-hydroxybenzylhydrazine (NSD 1015), and inhibitor of aromatic L-amino acid decarboxylase (DOPA decarboxylase) activity, was associated with a decreased concentration of dopamine in the median eminence and pronounced reduction in the release of dopamine into hypophysial portal blood. , [Neurochemical study of effects of the new anxiolytic drugs afobazol and ladasten on the synthesis and metabolism of monoamines and their metabolites in the brain structures of Wistar rat on the model of monoamine synthesis blockade induced by aromatic amino acid decarboxylase inhibitor NSD-1015]., DOPA was measured in the anterior pituitary and hypothalamic-hypophysial portal blood after treatment with NSD-1015, a DOPA decarboxylase inhibitor. , Central action of an inhibitor of brain dopa-decarboxylase, NSD-1015, on cyanamide-induced alcohol drinking in rats., The role of L-DOPA itself was investigated by administering several doses of an aromatic L-amino acid decarboxylase inhibitor, NSD 1015, prior to 100 mg/kg L-DOPA to 5-day-old rats. , The centrally acting aromatic amino acid dopa decarboxylase (AADC) inhibitor, 3-hydroxybenzyl hydrazine (NSD-1015), is widely used to study the neurotransmitter-like actions of L-DOPA. , Furthermore, the ethanol-induced enhancement of 3,4-dihydroxyphenylalanine accumulation in the mesolimbic dopamine terminal area after NSD 1015 (an inhibitor of l-aromatic amino acid decarboxylase) was completely antagonized by mecamylamine in doses (3.0 and 6.0 mg/kg) that exerted no effects per se., The acetylcholinesterase inhibitor physostigmine (0.5 mg/kg s.c.) enhanced L-dihydroxyphenylalanine (DOPA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in both the corpus striatum and limbic areas (nucleus accumbens) after inhibition of aromatic amino acid decarboxylase with NSD-1015, indicating an enhanced synthesis of dopamine in these brain regions., Estradiol benzoate-treated rats had significantly lower anterior pituitary DOPA accumulation after intraperitoneal administration of 3,4-hydroxybenzyl-hydrazine dihydrochloride (NSD-1015), an irreversible inhibitor of L-aromatic amino acid decarboxylase whereas methylene blue did not affect anterior pituitary DOPA accumulation when compared to controls., The accumulation of dihydroxyphenylalanine (DOPA) following administration of the L-aromatic amino acid decarboxylase inhibitor, NSD 1015, was used to estimate DA synthesis., Inhibition of PE synthesis by i.p. injection of the aromatic L-amino acid decarboxylase inhibitor, NSD 1015, produced a reversal of the effects of MDL 72,145 and Ro 19-6327., After 42 hr of abstinence, rats were challenged with either cocaine (15 mg/kg, ip) or saline, followed by the aromatic L-amino acid decarboxylase inhibitor 3-hydroxybenzylhydrazine (NSD-1015; 100 mg/kg, ip)., Following motor activity observations, the cerebral aromatic L-amino acid decarboxylase inhibitor NSD-1015 (100 mg kg-1 intraperitoneally) was administered and 30 min. later the animals were decapitated for subsequent analysis of the accumulated forebrain DOPA and 5-HTP levels, as an estimate of the rate of monoamine synthesis., The utility of this technique was demonstrated by comparing the effects on the scans of halothane and pentobarbital anesthesia and by the administration of NSD 1015, a peripheral and central inhibitor of L-aromatic amino-acid decarboxylase, between back-to-back scans., Addition of the aromatic amino acid decarboxylase inhibitor, 3-hydroxybenzylhydrazine (NSD 1015), prevented the formation of N-acetylcompounds from L-[3H]tyrosine, without resulting in an accumulation of label in L-DOPA., The effects of the peripheral aromatic amino acid decarboxylase (AADC) inhibitors, carbidopa and benserazide, and the central AADC inhibitor, 3-hydroxybenzylhydrazine (NSD-1015) on peripheral and brain monoamine oxidase (MAO) A and B activity were investigated in the rat., Although the putative role of NSD-1015 is as an aromatic amino acid decarboxylase inhibitor, the present results demonstrate that, either as a result of this function and/or in addition to this role, NSD-1015 is a potent activator of the release of dopamine., The aromatic amino acid decarboxylase inhibitor, NSD-1015, increases release of dopamine: response characteristics., The central aromatic amino acid DOPA decarboxylase inhibitor, NSD-1015, does not inhibit L-DOPA-induced circling in unilateral 6-OHDA-lesioned-rats., The L-aromatic amino acid decarboxylase inhibitor, NSD-1015 (3-hydroxybenzylhydrazine dihydrochloride) was then given ICV twice daily in a volume of 5.0 microliters in the following doses: 0.005, 0.01, 0.1 and 1.0 micrograms., Although the putative role of NSD-1015 is as an aromatic amino acid decarboxylase inhibitor, the present results demonstrate that, either as a result of this function and/or in addition to this role, NSD-1015 is a potent activator of the release of dopamine..[SEP]Relations: aromatic L-amino acid decarboxylase deficiency has relations: disease_protein with DDC, disease_protein with DDC, disease_disease with neurometabolic disease, disease_disease with neurometabolic disease, disease_phenotype_positive with Nasal obstruction, disease_phenotype_positive with Nasal obstruction, disease_phenotype_positive with Gastroesophageal reflux, disease_phenotype_positive with Gastroesophageal reflux. aromatic-L-amino-acid decarboxylase activity has relations: molfunc_protein with DDC, molfunc_protein with DDC. Definitions: saline defined as following: A crystalloid solution that contains 9.0g of SODIUM CHLORIDE per liter of water. It has a variety of uses, including: as a CONTACT LENS SOLUTION, in OPHTHALMIC SOLUTIONS and NASAL LAVAGE, in wound irrigation, and for FLUID THERAPY.. l-dopa defined as following: The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.. DOPA defined as following: A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific.. tryptophan hydroxylase defined as following: An enzyme that catalyzes the hydroxylation of TRYPTOPHAN to 5-HYDROXYTRYPTOPHAN in the presence of NADPH and molecular oxygen. It is important in the biosynthesis of SEROTONIN.. pargyline defined as following: A monoamine oxidase inhibitor with antihypertensive properties.. 5-HTP defined as following: A racemic mixture of 5-hydroxytryptophan (5-HTP), a precursor to the neurotransmitter serotonin with anti-depressant, analgesic and appetite-suppressant activities. DL-5-HTP is decarboxylated to serotonin by aromatic-L-amino-acid decarboxylase, and results in increased serotonin levels within the brain. Mediated through serotonin receptors, elevated levels of serotonin causes increased serotonin neurotransmissions, hence leading to release of depression, pain and appetite.. TPH defined as following: Human TPH1 wild-type allele is located within 11p15.3-p14 and is approximately 25 kb in length. This allele, which encodes tryptophan 5-hydroxylase 1 protein, is involved in tryptophan metabolism.. AADC defined as following: Human DDC wild-type allele is located in the vicinity of 7p12.2 and is approximately 107 kb in length. This allele, which encodes aromatic-L-amino-acid decarboxylase protein, is involved in monoamine neurotransmitter synthesis. Mutation of the gene is associated with aromatic L-amino-acid decarboxylase deficiency (AADCD).. aromatic L-amino acid decarboxylase defined as following: Aromatic-L-amino-acid decarboxylase (480 aa, ~54 kDa) is encoded by the human DDC gene. This protein plays a role in the conversion of amino acids to monoamine neurotransmitters.. acetylcholinesterase inhibitor defined as following: Any substance that inhibits acetylcholinesterase (AchE), an enzyme that breaks down acetylcholine (Ach) in the synaptic cleft. Inhibition of acetylcholinesterase results in an increase in the level and duration of action of acetylcholine.. tyrosine hydroxylase defined as following: An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 1.14.16.2.. 3,4-dihydroxyphenylacetic acid defined as following: A deaminated metabolite of LEVODOPA.. 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.. neurotransmitter defined as following: Endogenous signaling molecules secreted by neurons that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, neurohormones, and neurohumors, whether or not acting at synapses.. TH defined as following: Tyrosine 3-monooxygenase (528 aa, ~59 kDa) is encoded by the human TH gene. This protein plays a role in the synthesis of dopamine from L-tyrosine.. dopamine defined as following: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.. rat defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. MnCl2 defined as following: The dichloride salt of manganese, an essential trace element and a cofactor for many enzymes involved in a variety of biological activities in cells, with potential immunomodulating activity. Upon administration, manganese may act as an adjuvant and induce both humoral and cellular immune responses.. DOPA decarboxylase defined as following: One of the AROMATIC-L-AMINO-ACID DECARBOXYLASES, this enzyme is responsible for the conversion of DOPA to DOPAMINE. It is of clinical importance in the treatment of Parkinson's disease.. carbidopa defined as following: An inhibitor of DOPA DECARBOXYLASE that prevents conversion of LEVODOPA to dopamine. It is used in PARKINSON DISEASE to reduce peripheral adverse effects of LEVODOPA. It has no anti-parkinson activity by itself.. aromatic amino acid decarboxylase defined as following: An enzyme group with broad specificity. The enzymes decarboxylate a range of aromatic amino acids including dihydroxyphenylalanine (DOPA DECARBOXYLASE); TRYPTOPHAN; and HYDROXYTRYPTOPHAN.. 5-hydroxytryptamine defined as following: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.. methylene blue defined as following: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits GUANYLATE CYCLASE, and has been used to treat cyanide poisoning and to lower levels of METHEMOGLOBIN.. 5-hydroxytryptophan defined as following: The immediate precursor in the biosynthesis of SEROTONIN from tryptophan. It is used as an antiepileptic and antidepressant.. 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]. benserazide defined as following: An inhibitor of DOPA DECARBOXYLASE that does not enter the central nervous system. It is often given with LEVODOPA in the treatment of parkinsonism to prevent the conversion of levodopa to dopamine in the periphery, thereby increasing the amount that reaches the central nervous system and reducing the required dose. It has no antiparkinson actions when given alone.. PE defined as following: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to an ethanolamine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and ethanolamine and 2 moles of fatty acids.. mecamylamine defined as following: A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool.. aromatic amino acid decarboxylase inhibitor defined as following: Compounds and drugs that block or inhibit the enzymatic action of AROMATIC AMINO ACID DECARBOXYLASES. Pharmaceutical agents in this category are used in conjunction with LEVODOPA in order to slow its metabolism.. halothane defined as following: A nonflammable, halogenated, hydrocarbon anesthetic that provides relatively rapid induction with little or no excitement. Analgesia may not be adequate. NITROUS OXIDE is often given concomitantly. Because halothane may not produce sufficient muscle relaxation, supplemental neuromuscular blocking agents may be required. (From AMA Drug Evaluations Annual, 1994, p178). monoamine oxidase inhibitor defined as following: A chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines. (From Gilman, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p414). CHE defined as following: A Northeast Caucasian language spoken mostly in the Chechen Republic.. physostigmine defined as following: A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity.. peripheral defined as following: On or near an edge or constituting an outer boundary; the outer area.. metabolites defined as following: Any substance involved in metabolism, either as a product of metabolism or as necessary for metabolism.. Aromatic L-Amino Acid Decarboxylase defined as following: This gene plays a role in the synthesis of monoamine neurotransmitters..", "label": "yes"}
{"id": "converted_3321", "sentence1": "Is there a vaccine for rotavirus?", "sentence2": "Safety and Immunogenicity of Pentavalent Rotavirus Vaccine (RV5), This study compares the safety and immunogenicity of pentavalent rotavirus vaccine (RV5), Effectiveness of rotavirus pentavalent vaccine, rotavirus pentavalent vaccine (RotaTeq®) as a sole vaccine, We describe rotavirus vaccine coverage and missed opportunities for rotavirus vaccination., CONCLUSIONS\n\nAddressing missed opportunities for rotavirus vaccination is essential to achieving the 80% rotavirus vaccine coverage target outlined by Healthy People 2020., Complete rotavirus vaccine coverage could be improved to 81% if all missed opportunities within the ACIP-recommended schedule were addressed., RESULTS\n\nThe national coverage for rotavirus vaccine achieved a year after the introduction was 89% for one dose and 82% for two doses, respectively., CONCLUSIONS\n\nNorway achieved a high national coverage and excellent adherence with the strict age limits for rotavirus vaccine administration during the first year of introduction, indicating robustness of the national immunisation programme., Upper age limit recommendations for rotavirus vaccine administration contributed to suboptimal vaccination coverage., Catching-up with pentavalent vaccine: Exploring reasons behind lower rotavirus vaccine coverage in El Salvador., US Rotavirus Vaccine Efficacy Group., We describe rotavirus vaccine coverage and missed opportunities for rotavirus vaccination., Rotavirus vaccines: a story of success., Clinical and immunological studies of rotavirus vaccines., Impact of rotavirus vaccine on rotavirus diarrhoea in countries of East and Southern Africa., Rotavirus diarrheal episodes were identified by ELISA., The decrease in rotavirus positivity was inversely related to increase in rotavirus vaccine coverage showing impact of rotavirus vaccines., We described trends in rotavirus positivity among tested stool samples before and after rotavirus vaccine introduction., The RIT 4237 bovine rotavirus vaccine has served as a useful model for rotavirus vaccination, but the vaccine will not be further developed or tested., Only the RRV vaccine induced a low level of protection against rotavirus diarrhea mainly of serotype G1 specificity., It is recommended that new rotavirus vaccine candidates be developed at cheaper price to speed up the introduction of rotavirus immunization in the developing world in general., Review of rotavirus vaccine trials in Finland., Risk of intussusception after monovalent rotavirus vaccination., Rotavirus vaccines are underused compared with other routine vaccines., With rotavirus vaccines now available globally , it will be useful to assemble the available evidence on the epidemiology and burden of rotavirus gastroenteritis in India , in order to weigh the urgency of introducing a vaccine to help control rotavirus disease, Is there evidence that rotavirus vaccines are effective in preventing acute gastroenteritis complications such as dehydration and hospitalization, With the introduction of new rotavirus vaccines in sight , rotavirus gastroenteritis may be regarded as the single most frequent vaccine-preventable disease among children in the EU, With the recent introduction of the two rotavirus vaccines , RotaTeq and Rotarix , in many countries , it appears that the total number of hospitalizations due to rotavirus infections is being reduced , at least in developed countries that implemented a universal immunization program, Change in rotavirus epidemiology in northeast Florida after the introduction of rotavirus vaccine, With the recent postlicensure identification of an increased risk of intussusception with rotavirus vaccine , the 14 Latin American countries currently using rotavirus vaccine must now weigh the health benefits versus risks to assess whether to continue vaccination, Impact of rotavirus vaccines on rotavirus disease, With safe and efficacious rotavirus vaccines now on the verge of widespread adoption , researchers can be vital advocates for their uptake into routine immunization programs, Rotavirus vaccine RIX4414 (Rotarix™): a pharmacoeconomic review of its use in the prevention of rotavirus gastroenteritis in developed countries., In addition, various naturalistic studies have demonstrated 'real-world' effectiveness after the introduction of widespread rotavirus vaccination programmes in the community setting., The monovalent rotavirus vaccine RIX4414 (Rotarix™) is administered as a two-dose oral series in infants and has demonstrated protective efficacy against RVGE in clinical trials conducted in developed countries., Numerous cost-effectiveness analyses have been conducted in developed countries in which a universal rotavirus vaccination programme using RIX4414 was compared with no universal rotavirus vaccination programme., It is also difficult to draw conclusions regarding the cost effectiveness of rotavirus vaccine RIX4414 relative to that of the pentavalent rotavirus vaccine, which is administered as a three-dose oral series., Although indirect comparisons in cost-effectiveness analyses indicate that RIX4414 provided more favourable incremental cost-effectiveness ratios when each vaccine was compared with no universal rotavirus vaccination programme, results were generally sensitive to vaccine costs., A rotavirus vaccine for prophylaxis of infants against rotavirus gastroenteritis., A live attenuated monovalent rotavirus vaccine (Rotarix) containing human rotavirus strain RIX4414 of G1P1A P[8] specificity is being developed to meet the global need., Rotarix significantly reduced rotavirus gastroenteritis episodes and rotavirus-related hospitalizations in vaccinated infants compared with placebo recipients (P < 0.05)., We describe the intussusception epidemiology prior to rotavirus vaccine, temporal association of intussusception cases to administration of rotavirus vaccine, and estimate the additional number of intussusception cases that may be associated with rotavirus vaccine., Epidemiology of intussusception before and after rotavirus vaccine introduction in Fiji., In 2012, Fiji introduced rotavirus vaccine (Rotarix, GSK) into the national immunisation schedule., Four trials of RIT 4237 bovine rotavirus vaccine, one trial of group A RRV-1 rhesus rotavirus vaccine, and one trial of rhesus-human reassortant rotavirus vaccines D x RRV and DS1 x RRV were carried out between 1983-1989., Problems associated with the use of any oral rotavirus vaccine include acid lability of the vaccine virus, which requires buffering, and a slight but significant interference of oral poliovirus vaccine with the uptake of rotavirus vaccine., In the near future, oral heterologous rotavirus vaccines may be available for prevention of severe rotavirus gastroenteritis., There was no apparent difference between bovine and rhesus-based rotavirus vaccines in the protective efficacy against severe rotavirus gastroenteritis., Efficacy studies of this vaccine in 6-12 month-old children gave results characteristic of the performance of oral rotavirus vaccines in general: 58% protective efficacy against any rotavirus gastroenteritis and 82% against \"clinically significant\" gastroenteritis., Live oral rotavirus vaccine strain RIT 4237, derived from group A bovine rotavirus NCDV, was given to human volunteers in Tampere, Finland in 1982., Targeted efforts to evaluate indirect effects of rotavirus vaccine in low income countries are required to understand the total impact of rotavirus vaccine on the global burden of rotavirus disease., Widespread introduction of rotavirus vaccines has led to major reductions in the burden of rotavirus gastroenteritis worldwide., While rotavirus vaccine indirect effects have been demonstrated in high and middle income countries, there are very little data from low income countries where force of infection, population structures and vaccine schedules differ., Measuring indirect effects of rotavirus vaccine in low income countries., Intussusception among recipients of rotavirus vaccine: reports to the vaccine adverse event reporting system., Rotavirus vaccine was licensed on August 31, 1998, and subsequently recommended for routine use among infants., To describe the cases of intussusception among rotavirus vaccine recipients reported to the Vaccine Adverse Event Reporting System from October 1998 through December 1999., Infants vaccinated with rotavirus vaccine in the United States., There were 98 confirmed cases of intussusception after vaccination with rotavirus vaccine reported to the Vaccine Adverse Event Reporting System; 60 of these developed intussusception within 1 week after vaccination., Using a passive surveillance system for vaccine adverse events, we observed at least a fourfold increase over the expected number of intussusception cases occurring within 1 week of receipt of rotavirus vaccine., Other studies were initiated to further define the relationship between rotavirus vaccine and intussusception., In light of these and other data, the rotavirus vaccine manufacturer voluntarily removed its product from the market, and the recommendation for routine use of rotavirus vaccine among US infants has been withdrawn., To review the biology, immunology, and virology of rotavirus infections and describe the efforts towards the construction of vaccines using human and animal rotaviruses., In August 1998 the Food and Drug Administration in the United States approved the licensure of a rotavirus vaccine.[SEP]Relations: Rotavirus vaccine has relations: drug_drug with Sirolimus, drug_drug with Sirolimus, drug_drug with Sirolimus, drug_drug with Sirolimus, drug_drug with Mitomycin, drug_drug with Mitomycin, drug_drug with Mitomycin, drug_drug with Mitomycin, drug_drug with Flunisolide, drug_drug with Flunisolide. Definitions: rotavirus vaccines defined as following: Vaccines or candidate vaccines used to prevent infection with ROTAVIRUS.. rotavirus defined as following: rotavirus vaccine, tetravalent, live, oral
. acid defined as following: Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. (Grant & Hackh's Chemical Dictionary, 5th ed). dehydration defined as following: The condition that results from excessive loss of water from a living organism.. 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.. gastroenteritis defined as following: INFLAMMATION of any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM. Causes of gastroenteritis are many including genetic, infection, HYPERSENSITIVITY, drug effects, and CANCER.. human defined as following: Members of the species Homo sapiens.. rotavirus gastroenteritis defined as following: Enteritis attributed to the rotavirus.. rotavirus disease defined as following: Infection with any of the rotaviruses. Specific infections include human infantile diarrhea, neonatal calf diarrhea, and epidemic diarrhea of infant mice.. oral poliovirus vaccine defined as following: A live vaccine containing attenuated poliovirus, types I, II, and III, grown in monkey kidney cell tissue culture, used for routine immunization of children against polio. This vaccine induces long-lasting intestinal and humoral immunity. Killed vaccine induces only humoral immunity. Oral poliovirus vaccine should not be administered to immunocompromised individuals or their household contacts. (Dorland, 28th ed). 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.. intussusception defined as following: A form of intestinal obstruction caused by the PROLAPSE of a part of the intestine into the adjoining intestinal lumen. There are four types: colic, involving segments of the LARGE INTESTINE; enteric, involving only the SMALL INTESTINE; ileocecal, in which the ILEOCECAL VALVE prolapses into the CECUM, drawing the ILEUM along with it; and ileocolic, in which the ileum prolapses through the ileocecal valve into the COLON.. product defined as following: Participant material that is brought forth (produced) in the act (e.g., specimen in a specimen collection, access or drainage in a placement service, medication package in a dispense service). It does not matter whether the material produced had existence prior to the service, or whether it is created in the service (e.g., in supply services the product is taken from a stock).
. RIT defined as following: Human RIT1 wild-type allele is located in the vicinity of 1q22 and is approximately 14 kb in length. This allele, which encodes GTP-binding protein Rit1, is involved in signaling pathway regulation. Mutation of the gene is associated with Noonan syndrome type 8.. GSK defined as following: Catalysis of the reaction: ATP + tau-protein = ADP + O-phospho-tau-protein. [EC:2.7.11.26, MetaCyc:TAU-PROTEIN-KINASE-RXN].", "label": "yes"}
{"id": "converted_993", "sentence1": "Are there clinical trials using stem cells for the treatment of cardiac disease?", "sentence2": "Therapy with mesenchymal stem cells is one of the promising tools to improve outcomes after myocardial infarction. Adipose-derived stem cells (ASCs) are an ideal source of mesenchymal stem cells due to their abundance and ease of preparation., Furthermore, several ongoing clinical trials using ASCs are producing promising results for heart diseases., Among the cell types under investigation, adult mesenchymal stem cells are widely studied, and in early stage, clinical studies show promise for repair and regeneration of cardiac tissues., Accumulating data from preclinical and early phase clinical trials document their safety when delivered as either autologous or allogeneic forms in a range of cardiovascular diseases, but also importantly define parameters of clinical efficacy that justify further investigation in larger clinical trials. , several ongoing clinical trials using ASCs are producing promising results for heart diseases. , Clinical application of adult stem cells for therapy for cardiac disease., Stem cell-based therapies have the potential to fundamentally transform the treatment of ischemic cardiac injury and heart failure by achieving what would have been unthinkable only a few years ago-the Holy Grail of myocardial regeneration. Recent therapeutic approaches involve bone marrow (BM)-derived mononuclear cells and their subsets such as mesenchymal stem/stromal cells (MSCs), endothelial progenitor cells as well as adipose tissue-derived MSCs, cardiac tissue-derived stem cells, and cell combinations. Clinical trials employing these cells have demonstrated that cellular therapy is feasible and safe., Accumulating data from preclinical and early phase clinical trials document their safety when delivered as either autologous or allogeneic forms in a range of cardiovascular diseases, but also importantly define parameters of clinical efficacy that justify further investigation in larger clinical trials., se of stem and precursor cells as a therapeutic agent for chronically injured organs. Among the cell types under investigation, adult mesenchymal stem cells are widely studied, and in early stage, clinical studies show promise for repair and regeneration of cardiac tissues. , Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. , Small uncontrolled clinical trials have demonstrated cardiac stem cells as a treatment option for cardiomyopathy., Stem cell populations are rapidly increasing, and we are still in the search of optimal cell types to use in clinical trials as bone marrow stem cells did not show significant improvement in cardiac function following transplantation., Several clinical trials using adult stem cell have shown improvements in cardiac function, however, the mechanism of their action is unclear and widespread tissue regeneration is not evident., As we await results from larger and more prolonged clinical trials, the science of stem cell therapy in cardiac disease keeps progressing., Stem cell therapy for treatment of cardiac disease has shown therapeutic potential., It should be noted that stem cell therapy is not limited to the treatment of ischemic cardiac disease., Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials., This series of papers focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies., Cell transplantation to repair or regenerate injured myocardium is a new frontier in the treatment of cardiovascular disease. , Current therapies only delay progression of the cardiac disease or replace the diseased heart with cardiac transplantation. Stem cells represent a recently discovered novel approach to the treatment of cardiac failure that may facilitate the replacement of diseased cardiac tissue and subsequently lead to improved cardiac function and cardiac regeneration., Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. This series of papers focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies., Stem cell therapy for treatment of cardiac disease has shown therapeutic potential., Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. This series of papers focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies., It should be noted that stem cell therapy is not limited to the treatment of ischemic cardiac disease. Non-ischemic cardiomyopathy, peripheral vascular disease, and aging may be treated by stem cells., Recent clinical trials have achieved favorable initial endpoints with improvements in cardiac function and clinical symptoms following cellular therapy., we consider how cardiac stem cell biology has led us into clinical trials, and we suggest that achieving true cardiac regeneration in patients may ultimately require resolution of critical controversies in experimental cardiac regeneration., Cell-based therapies and tissue engineering provide new promising platforms to develop upcoming therapeutic options. Initial clinical trials were able to generate promising results. A variety of different stem cell types have been used for the clinical application. , Insights gained from clinical trials of adult stem cells, together with fundamental scientific advances in cardiac stem cell and regenerative biology, are beginning to yield potential new targets and strategies for regenerative therapies. , Early animal trials have demonstrated the ability to improve cardiac function by transfer of HSCs into the myocardium, and early human studies have demonstrated the feasibility and safety of this approach.[SEP]Relations: cardiac germ cell tumor has relations: disease_disease with heart neoplasm, disease_disease with heart neoplasm, disease_disease with malignant cardiac germ cell tumor, disease_disease with malignant cardiac germ cell tumor, disease_disease with extragonadal germ cell tumor, disease_disease with extragonadal germ cell tumor. heart disease has relations: disease_disease with cardiac ventricle disease, disease_disease with cardiac ventricle disease. cardiovascular disease has relations: disease_disease with heart disease, disease_disease with heart disease. Definitions: HSCs defined as following: Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood.. stem cells defined as following: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.. endothelial progenitor cells 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.. heart failure defined as following: Heart failure accompanied by EDEMA, such as swelling of the legs and ankles and congestion in the lungs.. cardiac diseases defined as following: Pathological conditions involving the HEART including its structural and functional abnormalities.. 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).. bone marrow stem cells defined as following: A hematopoietic stem cell found in the bone marrow.. cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. mesenchymal stem cells defined as following: An undifferentiated stromal cell with the ability to develop into the cells that form distinct mesenchymal tissues; such as bone, muscle, connective tissue, blood vessels, and lymphatic tissue.. adult stem cells defined as following: Mostly multipotent undifferentiated stem cells found in a specific tissue admixed with differentiated cells.. cardiac stem cell defined as following: Multipotent progenitor cells that are found in the fetal and adult heart that provide the myocardium with limited regenerating capability.. 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]. stem defined as following: A type of TRANSMISSION ELECTRON MICROSCOPY in which the object is examined directly by an extremely narrow electron beam scanning the specimen point-by-point and using the reactions of the electrons that are transmitted through the specimen to create the image. It should not be confused with SCANNING ELECTRON MICROSCOPY.. 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.. human defined as following: Members of the species Homo sapiens.. cells defined as following: The fundamental, structural, and functional units or subunits of living organisms. They are composed of CYTOPLASM containing various ORGANELLES and a CELL MEMBRANE boundary.. peripheral vascular disease defined as following: Pathological processes involving any one of the BLOOD VESSELS in the vasculature outside the HEART.. 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..", "label": "yes"}
{"id": "converted_2060", "sentence1": "Do brown fat cells produce heat?", "sentence2": "WAT and BAT are both involved in energy balance. WAT is mainly involved in the storage and mobilization of energy in the form of triglycerides, whereas BAT specializes in dissipating energy as heat during cold- or diet-induced thermogenesis., Because brown adipose tissue (BAT) dissipates energy in the form of heat, increasing energy expenditure by augmenting BAT-mediated thermogenesis may represent an approach to counter obesity and its complications., Classic brown fat and inducible beige fat both dissipate chemical energy in the form of heat through the actions of mitochondrial uncoupling protein 1. This nonshivering thermogenesis is crucial for mammals as a defense against cold and obesity/diabetes., Mitochondrial uncoupling protein 1 in brown fat cells produces heat by dissipating the energy generated by fatty acid and glucose oxidation., Brown fat biology and thermogenesis., Brown fat (brown adipose tissue, BAT) primary function is to produce heat. , Brown fat cells were classified into 6 types: Type 1 cells are fat-depleted cells filled with granular cytoplasm and are believed to be produced after oxidation of fat for heat production., Calorimetric measurements from cell suspensions showed that ATP increased basal heat production of isolated brown fat cells by approximately 40% but had no effect on the greater than fivefold increase in heat production seen with maximal adrenergic stimulation., Classic brown fat and inducible beige fat both dissipate chemical energy in the form of heat through the actions of mitochondrial uncoupling protein 1., Brown adipocytes oxidize fatty acids to produce heat in response to cold or to excessive energy intake; stimulation of brown fat development and function may thus counteract obesity., The occurrence of Types 1 and/or 6 cells that has been revealed in 65 out of the total 180 samples (36%), suggests that the oxidation of fat for the thermogenesis proceeds in the brown fat tissue and that brown fat cells partially undergo fat depletion., Brown fat cells were classified into 6 types: Type 1 cells are fat-depleted cells filled with granular cytoplasm and are believed to be produced after oxidation of fat for heat production., In response to cold, both classical brown fat and the newly identified \"beige\" or \"brite\" cells are activated by β-adrenergic signaling and catabolize stored lipids and carbohydrates to produce heat via UCP1, The ability of brown adipocytes (fat cells) to dissipate energy as heat shows great promise for the treatment of obesity and other metabolic disorders, Inappropriate heat dissipation ignites brown fat thermogenesis in mice with a mutant thyroid hormone receptor α1, Brown fat and vascular heat dissipation: The new cautionary tail, Brown adipose produces heat as a defense against hypothermia and obesity, and the appearance of brown-like adipocytes within white adipose tissue depots is associated with improved metabolic phenotypes. , In the same manner, marked ability to produce a considerable amount of heat was evidenced in brown fat tissue of children and teenagers. , Brown fat cells were classified into 6 types: Type 1 cells are fat-depleted cells filled with granular cytoplasm and are believed to be produced after oxidation of fat for heat production. , It is inferred that brown-adipose-tissue heat production is reduced during (and probably also some time after) anesthesia. , Parallel measurements of heat production and thermogenin content in brown fat cells during cold acclimation of rats., The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue instead of inducing fat accumulation can produce energy as heat., In response to cold, both classical brown fat and the newly identified \"beige\" or \"brite\" cells are activated by β-adrenergic signaling and catabolize stored lipids and carbohydrates to produce heat via UCP1., White adipose tissue stores energy reserves as fat, whereas the metabolic function of brown adipose tissue is lipid oxidation to produce heat., The main function of brown adipose tissue (BAT) is to produce heat in response to cold., Brown adipocytes oxidize fatty acids to produce heat in response to cold or caloric overfeeding., Brown fat (brown adipose tissue, BAT) primary function is to produce heat., Adipose tissue plays an active role in energy balance because it is not only a lipid storing and mobilizing tissue but consists of functionally specialized tissues able to produce heat (in brown adipose tissue) and to produce or release a vast number of so called adipokines or adipocytokines., Brown adipose tissue (BAT), a specialized fat that dissipates energy to produce heat, plays an important role in the regulation of energy balance., Brown adipose cells are specialized to dissipate chemical energy in the form of heat, as a physiological defence against cold and obesity., In the present study, the thermogenesis of human brown fat tissue was suggested chiefly with regard to the occurrence of Types 1 and/or 6 cells., In the same manner, marked ability to produce a considerable amount of heat was evidenced in brown fat tissue of children and teenagers., Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck., Brown and beige adipocytes expend chemical energy to produce heat and are therefore important in regulating body temperature and body weight., In human perirenal brown fat tissue, darkly stained fat-depleted cells (D) occupy, with other cell types (CR, CR'), an important part in the reversible heat production cycle of the brown fat tissue., Brown fat is a specialized fat depot that can increase energy expenditure and produce heat.[SEP]Relations: brown adipose tissue has relations: anatomy_anatomy with adipose tissue, anatomy_anatomy with adipose tissue. adipose tissue has relations: anatomy_anatomy with brown adipose tissue, anatomy_anatomy with brown adipose tissue, anatomy_protein_present with HEATR6, anatomy_protein_present with HEATR6, anatomy_protein_present with HEATR3, anatomy_protein_present with HEATR3, anatomy_protein_present with HEATR5A, anatomy_protein_present with HEATR5A. Definitions: lipids defined as following: A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed). Type 1 cells defined as following: used for classifying cell types, discovery of new cell types, or when type of cell is unknown; when comparing types of cells use CELL POPULATION STUDY.. CR defined as following: A quantitative measurement of the amount of creatinine present in a sample.. Mitochondrial uncoupling protein 1 defined as following: A mitochondrial uncoupling protein that is expressed in BROWN ADIPOSE TISSUE. It is critical for NONSHIVERING THERMOGENESIS to prevent heat loss in NEONATES.. brown adipocytes defined as following: Fat cells with dark coloration due to the densely packed MITOCHONDRIA. They contain numerous small lipid droplets or vacuoles. Their stored lipids can be converted directly to energy as heat by the mitochondria.. UCP1 defined as following: This gene plays a role in proton transport.. fatty acid 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). brown adipose tissue defined as following: A thermogenic form of adipose tissue composed of BROWN ADIPOCYTES. It is found in newborns of many species including humans, and in hibernating mammals. Brown fat is richly vascularized, innervated, and densely packed with MITOCHONDRIA which can generate heat directly from the stored lipids.. BAT defined as following: An evidence-based treatment designed to modify behavior by increasing positive events and reinforcers, as well as decreasing negative events and consequences. It is frequently used for treating depression and anxiety.. neck defined as following: Part of the dendritic spine that connects the dendritic shaft to the head of the dendritic spine. [GOC:nln]. 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.. ATP defined as following: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.. Adipose tissue defined as following: Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.. triglycerides defined as following: An ester formed from GLYCEROL and three fatty acid groups.. beige adipocytes defined as following: Brown fat-like cells that develop in the WHITE FAT from non-MYOGENIC REGULATORY FACTOR 5 expressing CELL LINEAGE.. metabolic disorders defined as following: Generic term for diseases caused by an abnormal metabolic process. It can be congenital due to inherited enzyme abnormality (METABOLISM, INBORN ERRORS) or acquired due to disease of an endocrine organ or failure of a metabolically important organ such as the liver. (Stedman, 26th ed). rats defined as following: The common rat, Rattus norvegicus, often used as an experimental organism.. adipokines defined as following: Polypeptides produced by the ADIPOCYTES. They include LEPTIN; ADIPONECTIN; RESISTIN; and many cytokines of the immune system, such as TUMOR NECROSIS FACTOR-ALPHA; INTERLEUKIN-6; and COMPLEMENT FACTOR D (also known as ADIPSIN). They have potent autocrine, paracrine, and endocrine functions.. fat cells defined as following: Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals.. mammals defined as following: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.. humans defined as following: Members of the species Homo sapiens.. tissues defined as following: Collections of differentiated CELLS, such as EPITHELIUM; CONNECTIVE TISSUE; MUSCLES; and NERVE TISSUE. Tissues are cooperatively arranged to form organs with specialized functions such as RESPIRATION; DIGESTION; REPRODUCTION; MOVEMENT; and others.. 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.. hypothermia defined as following: Cold weather can affect your body in different ways. You can get frostbite, which is an injury to the body that is caused by freezing. Your body can also lose heat faster than you can produce it. That can cause hypothermia, or abnormally low body temperature. It can make you sleepy, confused, and clumsy. Because it happens gradually and affects your thinking, you may not realize you need help. That makes it especially dangerous. A body temperature below 95 °F (35 °C) is a medical emergency and can lead to death if not treated promptly.
Anyone who spends much time outdoors in cold weather can get hypothermia. You can also get it from being cold and wet, or under cold water for too long. Babies and old people are especially at risk. Babies can get it from sleeping in a cold room.
Centers for Disease Control and Prevention
. 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]. brown fat cells defined as following: Fat cells with dark coloration due to the densely packed MITOCHONDRIA. They contain numerous small lipid droplets or vacuoles. Their stored lipids can be converted directly to energy as heat by the mitochondria..", "label": "yes"}
{"id": "converted_994", "sentence1": "Is DNA methylation an epigenetic modification of chromatin related to gene expression?", "sentence2": "DNA methylation is a chemical modification of DNA involved in the regulation of gene expression by controlling the access to the DNA sequence. , Epigenetic marks such as DNA methylation play important biological roles in gene expression regulation and cellular differentiation during development., DNA methylation patterns are characterized by highly conserved developmental programs, but allow for divergent gene expression resulting from stochastic epigenetic drift or divergent environments., DNA methylation plays a critical role in the regulation of gene expression. , Epigenetic changes such as DNA methylation and histone methylation and acetylation alter gene expression at the level of transcription by upregulating, downregulating, or silencing genes completely., Dysregulation of epigenetic events can be pathological, leading to cardiovascular disease, neurological disorders, metabolic disorders, and cancer development., DNA methylation is a pervasive epigenetic DNA modification that strongly affects chromatin regulation and gene expression., Epigenetic control, which includes DNA methylation and histone modifications, leads to chromatin remodeling and regulated gene expression., Epigenetic modifications on the DNA sequence (DNA methylation) or on chromatin-associated proteins (i.e., histones) comprise the \"cellular epigenome\"; together these modifications play an important role in the regulation of gene expression., Epigenetics is a process involved in gene regulation, mediated via DNA methylation, histone modification, chromatin remodeling, and functional noncoding RNAs, which influences the accessibility of the underlying DNA to transcriptional regulatory factors that activate or repress expression., Significant progress has been made in the basic understanding of how various epigenetic changes such as DNA methylation, histone modification, miRNA expression, and higher order chromatin structure affect gene expression.[SEP]Relations: histone modification has relations: bioprocess_bioprocess with histone methylation, bioprocess_bioprocess with histone methylation, bioprocess_bioprocess with covalent chromatin modification, bioprocess_bioprocess with covalent chromatin modification, bioprocess_bioprocess with histone demethylation, bioprocess_bioprocess with histone demethylation, bioprocess_bioprocess with histone biotinylation, bioprocess_bioprocess with histone biotinylation, bioprocess_protein with PARP2, bioprocess_protein with PARP2. Definitions: histone modification defined as following: The covalent alteration of one or more amino acid residues within a histone protein. [GOC:krc]. 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.. DNA sequence defined as following: The sequence of nucleotide residues along a DNA chain.. metabolic disorders defined as following: Generic term for diseases caused by an abnormal metabolic process. It can be congenital due to inherited enzyme abnormality (METABOLISM, INBORN ERRORS) or acquired due to disease of an endocrine organ or failure of a metabolically important organ such as the liver. (Stedman, 26th ed). cardiovascular disease defined as following: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.. 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).. neurological disorders defined as following: Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.. chemical modification defined as following: A molecule that binds to a macromolecule and can change the structural properties of that macromolecule.. 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.. chromatin defined as following: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell..", "label": "yes"}
{"id": "converted_319", "sentence1": "Is microRNA(miRNA) 29 involved in post-ischemic cardiac remodeling?", "sentence2": "Myocardial ischaemia/reperfusion (I/R)-induced remodelling generally includes cell death (necrosis and apoptosis), myocyte hypertrophy, angiogenesis, cardiac fibrosis, and myocardial dysfunction. I, In addition, miR-21, -24, -133, -210, -494, and -499 appear to protect myocytes against I/R-induced apoptosis, whereas miR-1, -29, -199a, and -320 promote apoptosis, Myocardial fibrosis can be regulated by the miR-29 family, Studies using various in vivo, ex vivo, and in vitro models have suggested the possible involvement of miR-1, miR-21, miR-29, miR-92a, miR-133, miR-199a, and miR-320 in ischemia-reperfusion injury and/or remodeling after myocardial infarction., Among the MI-regulated miRNAs are members of the miR-29 family, which are down-regulated in the region of the heart adjacent to the infarct. The miR-29 family targets a cadre of mRNAs that encode proteins involved in fibrosis, including multiple collagens, fibrillins, and elastin. Thus, down-regulation of miR-29 would be predicted to derepress the expression of these mRNAs and enhance the fibrotic response. Indeed, down-regulation of miR-29 with anti-miRs in vitro and in vivo induces the expression of collagens, whereas over-expression of miR-29 in fibroblasts reduces collagen expression. We conclude that miR-29 acts as a regulator of cardiac fibrosis and represents a potential therapeutic target for tissue fibrosis in general.[SEP]Relations: ischemia reperfusion injury has relations: disease_protein with MIR148B, disease_protein with MIR148B, disease_protein with EFNA5, disease_protein with EFNA5. myocardial infarction has relations: disease_protein with MIR145, disease_protein with MIR145, disease_protein with MIR145, disease_protein with MIR145, disease_protein with MIR761, disease_protein with MIR761. Definitions: fibrosis defined as following: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.. collagens 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).. fibrillins defined as following: A family of extracellular matrix glycoproteins that is structurally similar to LATENT TGF-BETA BINDING PROTEINS, but contain additional TGF-beta binding domains, in addition to unique domains at their N and C-terminals. Fibrillins assemble into 10-12 nm MICROFIBRILS that function in a variety of cell interactions with the EXTRACELLULAR MATRIX and developmental processes such as ELASTIC TISSUE maintenance and assembly, and the targeting of growth factors to the extracellular matrix.. miR-21 defined as following: This gene is involved in the regulation of gene expression and plays an oncogenic role in hepatocellular, breast, esophageal, gastric, pancreatic, prostatic and squamous cell carcinomas, glioblastoma and glioma.. ischemia-reperfusion injury defined as following: Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA.. 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.. necrosis defined as following: A finding indicating the presence of cellular necrosis in a tissue specimen.. elastin defined as following: Elastin (786 aa, ~68 kDa) is encoded by the human ELN gene. This protein is involved in the elasticity of the extracellular matrix.. anti-miRs defined as following: Chemically-engineered oligonucleotides used to selectively inhibit expression of target genes through sequence-specific binding of corresponding microRNA (miRNA) sites.. miRNAs defined as following: Small double-stranded, non-protein coding RNAs, 21-25 nucleotides in length generated from single-stranded microRNA gene transcripts by the same RIBONUCLEASE III, Dicer, that produces small interfering RNAs (RNA, SMALL INTERFERING). They become part of the RNA-INDUCED SILENCING COMPLEX and repress the translation (TRANSLATION, GENETIC) of target RNA by binding to homologous 3'UTR region as an imperfect match. The small temporal RNAs (stRNAs), let-7 and lin-4, from C. elegans, are the first 2 miRNAs discovered, and are from a class of miRNAs involved in developmental timing.. infarct defined as following: Formation of an infarct, which is NECROSIS in tissue due to local ISCHEMIA resulting from obstruction of BLOOD CIRCULATION, most commonly by a THROMBUS or EMBOLUS.. Myocardial fibrosis defined as following: The accumulation of fibrotic tissue in the myocardium. This may result from chronic hypertension, myocardial infarction or cardiomyopathy and eventually lead to heart failure..", "label": "yes"}
{"id": "converted_1768", "sentence1": "Is there a role of regorafenib for sarcoma treatment?", "sentence2": "Regorafenib has been approved for third-line therapy., Study protocol of REGOSARC trial: activity and safety of regorafenib in advanced soft tissue sarcoma: a multinational, randomized, placebo-controlled, phase II trial., DISCUSSION: The design of this trial allows an assessment of regorafenib activity over placebo in four sarcoma strata and might provide evidence for launching a phase III trial., This case provides rationale for adding a Ewing sarcoma arm to SARC024, a phase II study of regorafenib, another multi-targeted kinase inhibitor, in patients with liposarcoma, osteosarcoma and Ewing and Ewing-like sarcomas (NCT02048371)., Thus, the Phase III studies with pazopanib, regorafenib, muramyl tripeptide (MTP) and ridaforolimus are extensively discussed as well as the biological rationale for the use of these compounds., Currently, regorafenib is examined in several clinical trials (mostly phase II) in different tumor entities, including renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and soft tissue sarcoma (STS)., Analysis of primary human sarcoma samples revealed direct cytotoxicity following exposure to sorafenib and regorafenib with a corresponding increase in ALDHbright cells (P<0.05)., Parametric and non-parametric statistical analyses were performed as appropriate.RESULTS: After functionally validating the CSC phenotype of ALDHbright sarcoma cells, we observed that sorafenib and regorafenib were cytotoxic to sarcoma cell lines (P<0.05), with a corresponding 1.4 - 2.8 fold increase in ALDHbright cells from baseline (P<0.05)., We evaluated survival and CSC phenotype in mice harboring sarcoma metastases after TKI therapy. We exposed dissociated primary sarcoma tumors to sorafenib, regorafenib, and pazopanib, and we used tissue microarray (TMA) and primary sarcoma samples to evaluate the frequency and intensity of CSC markers after neoadjuvant therapy with sorafenib and pazopanib. Parametric and non-parametric statistical analyses were performed as appropriate.RESULTS: After functionally validating the CSC phenotype of ALDHbright sarcoma cells, we observed that sorafenib and regorafenib were cytotoxic to sarcoma cell lines (P<0.05), with a corresponding 1.4 - 2.8 fold increase in ALDHbright cells from baseline (P<0.05)., We exposed dissociated primary sarcoma tumors to sorafenib, regorafenib, and pazopanib, and we used tissue microarray (TMA) and primary sarcoma samples to evaluate the frequency and intensity of CSC markers after neoadjuvant therapy with sorafenib and pazopanib. Parametric and non-parametric statistical analyses were performed as appropriate.RESULTS: After functionally validating the CSC phenotype of ALDHbright sarcoma cells, we observed that sorafenib and regorafenib were cytotoxic to sarcoma cell lines (P<0.05), with a corresponding 1.4 - 2.8 fold increase in ALDHbright cells from baseline (P<0.05)., We exposed dissociated primary sarcoma tumors to sorafenib, regorafenib, and pazopanib, and we used tissue microarray (TMA) and primary sarcoma samples to evaluate the frequency and intensity of CSC markers after neoadjuvant therapy with sorafenib and pazopanib. Parametric and non-parametric statistical analyses were performed as appropriate.RESULTS: After functionally validating the CSC phenotype of ALDHbright sarcoma cells, we observed that sorafenib and regorafenib were cytotoxic to sarcoma cell lines (P<0.05), with a corresponding 1.4 - 2.8 fold increase in ALDHbright cells from baseline (P<0.05). In contrast, we observed negligible effects on viability and CSC sub-populations with pazopanib., After functionally validating the CSC phenotype of ALDHbright sarcoma cells, we observed that sorafenib and regorafenib were cytotoxic to sarcoma cell lines (P < 0.05), with a corresponding 1.4 - 2.8 fold increase in ALDHbright cells from baseline (P < 0.05).[SEP]Relations: Regorafenib has relations: drug_drug with Sarilumab, drug_drug with Sarilumab, drug_drug with Sarecycline, drug_drug with Sarecycline, drug_drug with Afelimomab, drug_drug with Afelimomab, drug_drug with Lapatinib, drug_drug with Lapatinib, drug_drug with Sulfasalazine, drug_drug with Sulfasalazine. Definitions: RCC defined as following: A malignant epithelial neoplasm of the kidney characterized by the presence of lipid-containing clear cells within a vascular network. The tumor may metastasize to unusual sites and late metastasis is common.. pazopanib defined as following: A small molecule inhibitor of multiple protein tyrosine kinases with potential antineoplastic activity. Pazopanib selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, -2 and -3, c-kit and platelet derived growth factor receptor (PDGF-R), which may result in inhibition of angiogenesis in tumors in which these receptors are upregulated.. ridaforolimus defined as following: A small molecule and non-prodrug analogue of the lipophilic macrolide antibiotic rapamycin with potential antitumor activity. Ridaforolimus binds to and inhibits the mammalian target of rapamycin (mTOR), which may result in cell cycle arrest and, consequently, the inhibition of tumor cell growth and proliferation. Upregulated in some tumors, mTOR is a serine/threonine kinase involved in regulating cellular proliferation, motility, and survival that is located downstream of the PI3K/Akt signaling pathway.. 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.. Regorafenib defined as following: The anhydrous form of regorafenib, an orally bioavailable small molecule with potential antiangiogenic and antineoplastic activities. Regorafenib binds to and inhibits vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. VEGFRs are receptor tyrosine kinases that play important roles in tumor angiogenesis; the receptor tyrosine kinases RET, KIT, and PDGFR, and the serine/threonine-specific Raf kinase are involved in tumor cell signaling.. osteosarcoma defined as following: A usually aggressive malignant bone-forming mesenchymal neoplasm arising from the bone. It may arise de novo or from a pre-existing lesion of the bone. Pain and a palpable mass are the most frequent clinical sign and symptom. It may spread to other anatomic sites, particularly the lungs.. sarcoma defined as following: A malignant neoplasm arising exclusively from the soft tissues.. STS defined as following: An anionic surface-active agent used for its wetting properties in industry and used in medicine as an irritant and sclerosing agent for hemorrhoids and varicose veins.. 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.. liposarcoma defined as following: A malignant tumor derived from primitive or embryonal lipoblastic cells. It may be composed of well-differentiated fat cells or may be dedifferentiated: myxoid (LIPOSARCOMA, MYXOID), round-celled, or pleomorphic, usually in association with a rich network of capillaries. Recurrences are common and dedifferentiated liposarcomas metastasize to the lungs or serosal surfaces. (From Dorland, 27th ed; Stedman, 25th ed). soft tissue sarcoma defined as following: A malignant neoplasm arising from muscle tissue, adipose tissue, blood vessels, fibrous tissue, or other supportive tissues excluding the bones.. sorafenib defined as following: A synthetic compound targeting growth signaling and angiogenesis. Sorafenib blocks the enzyme RAF kinase, a critical component of the RAF/MEK/ERK signaling pathway that controls cell division and proliferation; in addition, sorafenib inhibits the VEGFR-2/PDGFR-beta signaling cascade, thereby blocking tumor angiogenesis.. regorafenib defined as following: The anhydrous form of regorafenib, an orally bioavailable small molecule with potential antiangiogenic and antineoplastic activities. Regorafenib binds to and inhibits vascular endothelial growth factor receptors (VEGFRs) 2 and 3, and Ret, Kit, PDGFR and Raf kinases, which may result in the inhibition of tumor angiogenesis and tumor cell proliferation. VEGFRs are receptor tyrosine kinases that play important roles in tumor angiogenesis; the receptor tyrosine kinases RET, KIT, and PDGFR, and the serine/threonine-specific Raf kinase are involved in tumor cell signaling..", "label": "yes"}
{"id": "converted_3590", "sentence1": "Does association with the nuclear pore promote gene silencing?", "sentence2": "Here, we show that the nucleoporin Nup358 plays an important role in this process. Nup358 localizes to the nuclear pore complex and to the cytoplasmic annulate lamellae (AL), and these structures dynamically associate with two mRNP granules: processing bodies (P bodies) and stress granules (SGs). , MicroRNA (miRNA)-guided mRNA repression, mediated by the miRNA-induced silencing complex (miRISC), is an important component of post-transcriptional gene silencing., To assess Tpr's role as an architectural element of the NPC, we have studied the sequential disassembly and reassembly of NPCs in mitotic cells, paralleled by studies of cells depleted of Tpr as a result of posttranscriptional tpr gene silencing by RNA interference (RNAi)., The results raise the possibility that NPC-localized protein desumoylation may be a key regulatory event preventing inappropriate pre-mRNA export., Silencing nuclear pore protein Tpr elicits a senescent-like phenotype in cancer cells.[SEP]Relations: nuclear pore has relations: cellcomp_protein with RAN, cellcomp_protein with RAN, cellcomp_protein with IPO5, cellcomp_protein with IPO5, cellcomp_protein with GLE1, cellcomp_protein with GLE1, cellcomp_protein with IPO7, cellcomp_protein with IPO7, cellcomp_protein with RGPD5, cellcomp_protein with RGPD5. Definitions: NPC defined as following: A carcinoma that originates in the EPITHELIUM of the NASOPHARYNX and includes four subtypes: keratinizing squamous cell, non-keratinizing, basaloid squamous cell, and PAPILLARY ADENOCARCINOMA. It is most prevalent in Southeast Asian populations and is associated with EPSTEIN-BARR VIRUS INFECTIONS. Somatic mutations associated with this cancer have been identified in NPCR, BAP1, UBAP1, ERBB2, ERBB3, MLL2, PIK3CA, KRAS, NRAS, and ARID1A genes.. Nup358 defined as following: Human RANBP2 wild-type allele is located in the vicinity of 2q12.3 and is approximately 66 kb in length. This allele, which encodes E3 SUMO-protein ligase RanBP2 protein, plays a role in both nuclear transport and protein SUMOylation. Mutation of the gene is associated with acute infection-induced encephalopathy 3. A chromosomal translocation t(2;2)(p23;q13) involving this gene and the ALK gene is associated with both inflammatory myofibroblastic tumor and, more rarely, myeloproliferative disorders.. pre-mRNA defined as following: A primary RNA transcript synthesized from a DNA template in eukaryotic nuclei which is post-transcriptionally modified and spliced to produce a mature mRNA.. cancer cells defined as following: Cells of, or derived from, a malignant tumor.. 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.. Tpr defined as following: Nucleoprotein TPR (2363 aa, ~267 kDa) is encoded by the human TPR gene. This protein plays a role in both mitotic spindle assembly and nuclear membrane transport.. 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.. nuclear pore complex defined as following: An opening through the NUCLEAR ENVELOPE formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the CELL NUCLEUS and which, under some conditions, acts as an ion channel.. stress granules defined as following: A dense aggregation in the cytosol composed of proteins and RNAs that appear when the cell is under stress. [GOC:ans, PMID:17284590, PMID:17601829, PMID:17967451, PMID:20368989]. nuclear pore defined as following: An opening through the NUCLEAR ENVELOPE formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the CELL NUCLEUS and which, under some conditions, acts as an ion channel..", "label": "yes"}
{"id": "converted_1466", "sentence1": "Is the HRC Ser96Ala variant associated with sudden cardiac death in patients with dilated cardiomyopathy?", "sentence2": "The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM., The Ser96Ala (S96A) mutation within the histidine rich Ca(2+) binding protein (HRC) has recently been linked to cardiac arrhythmias in idiopathic dilated cardiomyopathy patients, potentially attributable to an increase in spontaneous Ca(2+) release events., A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR) histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy., The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers., HRC has been linked with familiar cardiac conduction disease and an HRC polymorphism was shown to associate with malignant ventricular arrhythmias in the background of idiopathic dilated cardiomyopathy., A human genetic variant (Ser96Ala) in the sarcoplasmic reticulum (SR) histidine-rich Ca(2+)-binding (HRC) protein has been linked to ventricular arrhythmia and sudden death in dilated cardiomyopathy, The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM., The histidine-rich calcium binding protein (HRC) Ser96Ala polymorphism was shown to correlate with ventricular arrhythmias and sudden death only in dilated cardiomyopathy patients but not in healthy human carriers, The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy., These findings indicate that the HRC Ser96Ala variant increases the propensity of arrhythmogenic Ca(2+) waves in the stressed failing heart, suggesting a link between this genetic variant and life-threatening ventricular arrhythmias in human carriers.[SEP]Relations: dilated cardiomyopathy has relations: disease_phenotype_positive with Sudden cardiac death, disease_phenotype_positive with Sudden cardiac death, disease_phenotype_positive with Sudden death, disease_phenotype_positive with Sudden death, disease_protein with SLC22A5, disease_protein with SLC22A5, disease_protein with ABCC9, disease_protein with ABCC9. Sudden death has relations: disease_phenotype_positive with dilated cardiomyopathy, disease_phenotype_positive with dilated cardiomyopathy. Definitions: ventricular arrhythmia defined as following: An electrocardiographic finding of an atypical cardiac rhythm resulting from a pathologic process in the cardiac ventricles.. variant defined as following: An alteration or difference from a norm or standard.. human defined as following: Members of the species Homo sapiens.. sarcoplasmic reticulum defined as following: A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.. dilated cardiomyopathy defined as following: Cardiomyopathy which is characterized by dilation and contractile dysfunction of the left and right ventricles. It may be idiopathic, or it may result from a myocardial infarction, myocardial infection, or alcohol abuse. It is a cause of congestive heart failure.. 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.. 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.. 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.. 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.. 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). 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).", "label": "yes"}
{"id": "converted_1846", "sentence1": "Can Diabetes be caused by a defect in a potassium chanel?", "sentence2": "Mutations in KATP channel genes can result in hypo- or hypersecretion of insulin, as in neonatal diabetes mellitus and congenital hyperinsulinism, respectively., To date, all patients affected by neonatal diabetes due to a mutation in the pore-forming subunit of the channel (Kir6.2, KCNJ11) are heterozygous for the mutation. , e report the first clinical case of neonatal diabetes caused by a homozygous KCNJ11 mutation, Diffuse congenital hyperinsulinism in infancy (CHI-D) arises from mutations inactivating the KATP channel;, We report a case of a 6-week-old infant with diabetes mellitus based on a genetic defect in the sulfonylurea receptor 1 (SUR1), an ATP-sensitive potassium (KATP) channel protein., In diabetes, vascular KATP channel function is impaired.[SEP]Relations: Type I diabetes mellitus has relations: disease_phenotype_positive with transketolase deficiency, disease_phenotype_positive with transketolase deficiency, disease_phenotype_positive with vasculitis due to ADA2 deficiency, disease_phenotype_positive with vasculitis due to ADA2 deficiency, disease_phenotype_positive with immunodeficiency due to CD25 deficiency, disease_phenotype_positive with immunodeficiency due to CD25 deficiency, disease_phenotype_positive with methanol poisoning, disease_phenotype_positive with methanol poisoning. KCNJ11 has relations: pathway_protein with Defective ABCC8 can cause hypo- and hyper-glycemias, pathway_protein with Defective ABCC8 can cause hypo- and hyper-glycemias. Definitions: congenital hyperinsulinism defined as following: A familial, nontransient HYPOGLYCEMIA with defects in negative feedback of GLUCOSE-regulated INSULIN release. Clinical phenotypes include HYPOGLYCEMIA; HYPERINSULINEMIA; SEIZURES; COMA; and often large BIRTH WEIGHT. Several sub-types exist with the most common, type 1, associated with mutations on an ATP-BINDING CASSETTE TRANSPORTERS (subfamily C, member 8).. 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.. 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.. diabetes defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.. sulfonylurea receptor 1 defined as following: ATP-BINDING CASSETTE PROTEINS that are highly conserved and widely expressed in nature. They form an integral part of the ATP-sensitive potassium channel complex which has two intracellular nucleotide folds that bind to sulfonylureas and their analogs.. KATP channel defined as following: Heteromultimers of Kir6 channels (the pore portion) and sulfonylurea receptor (the regulatory portion) which affect function of the HEART; PANCREATIC BETA CELLS; and KIDNEY COLLECTING DUCTS. KATP channel blockers include GLIBENCLAMIDE and mitiglinide whereas openers include CROMAKALIM and minoxidil sulfate.. Mutations defined as following: The result of any gain, loss or alteration of the sequences comprising a gene, including all sequences transcribed into RNA.. Diabetes defined as following: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE..", "label": "yes"}
{"id": "converted_809", "sentence1": "Are conserved noncoding elements associated with developmental genes?", "sentence2": "Some characteristics of CNEs include their high frequency in mammalian genomes, their potential regulatory role in gene expression, and their enrichment in gene deserts nearby master developmental genes, we review recent findings that disruptions of CNEs, within or at long distance from the coding sequences of key genes involved in NCC development, result in neurocristopathies via the alteration of tissue- or stage-specific long-distance regulation of gene expression, Genomic regulatory blocks are chromosomal regions spanned by long clusters of highly conserved noncoding elements devoted to long-range regulation of developmental genes, Analysis of CNEs, at least some of which are candidate regulatory elements, suggests that ancestral CNEs partitioned between gene duplicates. These results help explain the evolutionary pathways by which the developmentally important family of FgfD molecules arose and the deduced principles that guided FgfD evolution are likely applicable to the evolution of developmental regulation in many vertebrate multigene families, Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control. On the loci of two developmental transcription factor genes, SOX3 and PAX6, we demonstrate that HCNEs conserved between human and zebrafish can be systematically and reliably tested for their regulatory function in multiple stable transgenes in zebrafish, and their genomic reach estimated with confidence using synteny conservation and HCNE density along these loci. HCNEs of both human and zebrafish function as specific developmental enhancers in zebrafish, We show that human HCNEs result in expression patterns in zebrafish equivalent to those in mouse, establishing zebrafish as a suitable model for large-scale testing of human developmental enhancers, HCNEs from the same area often drive overlapping patterns, suggesting that multiple regulatory inputs are required to achieve robust and precise complex expression patterns exhibited by developmental genes, Organization of conserved elements near key developmental regulators in vertebrate genomes, Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation, Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes, Metazoan genomes contain arrays of highly conserved noncoding elements (HCNEs) that span developmental regulatory genes and define regulatory domains, The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development, We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes., Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes., Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control., Metazoan genomes contain arrays of highly conserved noncoding elements (HCNEs) that span developmental regulatory genes and define regulatory domains., Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation., The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs)., Disruption of long-distance highly conserved noncoding elements in neurocristopathies., Fish-mammal genomic comparisons have proved powerful in identifying conserved noncoding elements likely to be cis-regulatory in nature, and the majority of those tested in vivo have been shown to act as tissue-specific enhancers associated with genes involved in transcriptional regulation of development., Despite this, attempts at unearthing genome-wide regulatory elements conserved throughout the vertebrate lineage using BLAST-like approaches have thus far detected noncoding conservation in only a few hundred genes, mostly associated with regulation of transcription and development., Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation., We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes., Organization of conserved elements near key developmental regulators in vertebrate genomes., Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control[SEP]Relations: transcription factor binding has relations: molfunc_protein with PARK7, molfunc_protein with PARK7, molfunc_protein with ARNT, molfunc_protein with ARNT, molfunc_protein with HOXA7, molfunc_protein with HOXA7, molfunc_protein with CEBPG, molfunc_protein with CEBPG. SLC12A3 has relations: anatomy_protein_absent with decidua, anatomy_protein_absent with decidua. Definitions: gene defined as following: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.. PAX6 defined as following: This gene plays a role in transcriptional regulation.. genome defined as following: Anatomical set of genes in all the chromosomes.. pleiotropic genes defined as following: A single gene that influences several distinct and seemly unrelated phenotypic outcomes.. conservation defined as following: The maintenance of certain characteristics in an unchanged condition.. SOX3 defined as following: This gene is involved in neuronal differentiation.. human defined as following: Members of the species Homo sapiens.. zebrafish defined as following: An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. Zebrafish is a model organism for drug assay and cancer research.. transgenes defined as following: Genes that are introduced into an organism using GENE TRANSFER TECHNIQUES.. transcription factors defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. developmental genes defined as following: Genes that determine the fate of a cell or CELLS in a region of the embryo during EMBRYONIC DEVELOPMENT.. vertebrate defined as following: Animals having a vertebral column, members of the phylum Chordata, subphylum Craniata comprising mammals, birds, reptiles, amphibians, and fishes..", "label": "yes"}
{"id": "converted_2349", "sentence1": "Do chromatin features predict genes associated with eQTLs?", "sentence2": "Using the random forest classifier, we found that genomic proximity plus five TF and chromatin features are able to predict>90% of target genes within 1 megabase of eQTLs, Using the random forest classifier, we found that genomic proximity plus five TF and chromatin features are able to predict >90% of target genes within 1 megabase of eQTLs., Cell type-specific gene expression in humans involves complex interactions between regulatory factors and DNA at enhancers and promoters. Mapping studies for expression quantitative trait loci (eQTLs), transcription factors (TFs) and chromatin markers have become widely used tools for identifying gene regulatory elements, but prediction of target genes remains a major challenge. Here, we integrate genome-wide data on TF-binding sites, chromatin markers and functional annotations to predict genes associated with human eQTLs. Using the random forest classifier, we found that genomic proximity plus five TF and chromatin features are able to predict >90% of target genes within 1 megabase of eQTLs. Despite being regularly used to map target genes, proximity is not a good indicator of eQTL targets for genes 150 kilobases away, but insulators, TF co-occurrence, open chromatin and functional similarities between TFs and genes are better indicators. Using all six features in the classifier achieved an area under the specificity and sensitivity curve of 0.91, much better compared with at most 0.75 for using any single feature. We hope this study will not only provide validation of eQTL-mapping studies, but also provide insight into the molecular mechanisms explaining how genetic variation can influence gene expression.[SEP]Relations: transcription factor binding has relations: molfunc_protein with C1QBP, molfunc_protein with C1QBP, molfunc_protein with METTL23, molfunc_protein with METTL23, molfunc_protein with ETS1, molfunc_protein with ETS1, molfunc_protein with CENPF, molfunc_protein with CENPF, molfunc_protein with AHR, molfunc_protein with AHR. Definitions: humans defined as following: Members of the species Homo sapiens.. TF defined as following: A person who was assigned to the male gender at birth based on physical characteristics but who self-identifies psychologically and emotionally as female.. 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).. promoters defined as following: A DNA sequence at which RNA polymerase binds and initiates transcription.. transcription factors defined as following: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.. 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.. chromatin defined as following: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell..", "label": "yes"}
{"id": "converted_4300", "sentence1": "Is istiratumab effective for pancreatic cancer?", "sentence2": "CONCLUSIONS: Istiratumab failed to improve the efficacy of SOC chemotherapy in this patient setting. [SEP]Definitions: pancreatic cancer defined as following: A primary or metastatic malignant tumor involving the pancreas. Representative examples include carcinoma and lymphoma..", "label": "no"}
{"id": "converted_4145", "sentence1": "Is atenolol metabolized by CYP2D6?", "sentence2": "The study analysed the prescribing and dispensing of CYP2D6 drugs (metoprolol, donepezil, galantamine, codeine, tamoxifen) together with CYP2D6-blocking SSRIs (paroxetine/fluoxetine) or SSRIs without significant CYP2D6 inhibition (citalopram/escitalopram/sertraline), and the related prescribing of CYP2D6-independent comparator drugs (atenolol, rivastigmine, propoxyphene, anastrozole).[SEP]Relations: Atenolol has relations: drug_protein with CYP2D6, drug_protein with CYP2D6, drug_drug with NN344, drug_drug with NN344, drug_protein with ADRB2, drug_protein with ADRB2, drug_drug with Isocarboxazid, drug_drug with Isocarboxazid, drug_protein with ABCB11, drug_protein with ABCB11. Definitions: propoxyphene defined as following: The d-isomer of synthetic diphenyl propionate derivative propoxyphene, with narcotic analgesic effect. This agent mimics the effects of the endogenous opiate dextropropoxyphene, by binding to mu receptors located throughout the central nervous system. The binding results in GTP to GDP exchanges on the mu-G-protein complex, by which effector adenylate cyclase is inactivated thereby decreasing intracellular cAMP. This, in turn, inhibits the release of various nociceptive neurotransmitters, such as substance P, gamma-aminobutyric acid (GABA), dopamine, acetylcholine, noradrenaline, vasopressin, and somatostatin. In addition, dextropropoxyphene closes N-type voltage-gated calcium channels and opens calcium-dependent inwardly rectifying potassium channels. This results in hyperpolarization, thereby reducing neuronal excitability, which further decreases the perception of pain.. SSRIs defined as following: Any agent that increases the extracellular level of the neurotransmitter serotonin (5-HT) by inhibiting its reuptake into the presynaptic cell. Increased level in the synaptic cleft prolongs the action of 5-HT on the postsynaptic receptor. This type of agent is typically used as an antidepressant and in the treatment of anxiety disorders and some personality disorders. They are also typically effective and used in treating some cases of insomnia.. donepezil defined as following: The hydrochloride salt of a piperidine derivative with neurocognitive-enhancing activity. Donepezil reversibly inhibits acetylcholinesterase, thereby blocking the hydrolysis of the neurotransmitter acetylcholine and, consequently, increasing its activity. This agent may improve neurocognitive function in Alzheimer's disease, reduce sedation associated with opioid treatment of cancer pain, and improve neurocognitive function in patients who have received radiation therapy for primary brain tumors or brain metastases.. galantamine defined as following: A benzazepine derived from norbelladine. It is found in GALANTHUS and other AMARYLLIDACEAE. It is a cholinesterase inhibitor that has been used to reverse the muscular effects of GALLAMINE TRIETHIODIDE and TUBOCURARINE and has been studied as a treatment for ALZHEIMER DISEASE and other central nervous system disorders.. codeine defined as following: An opioid analgesic related to MORPHINE but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough.. tamoxifen defined as following: One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.. rivastigmine defined as following: A carbamate-derived reversible CHOLINESTERASE INHIBITOR that is selective for the CENTRAL NERVOUS SYSTEM and is used for the treatment of DEMENTIA in ALZHEIMER DISEASE and PARKINSON DISEASE.. metoprolol defined as following: A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS.. atenolol defined as following: A cardioselective beta-1 adrenergic blocker possessing properties and potency similar to PROPRANOLOL, but without a negative inotropic effect.. CYP2D6 defined as following: Cytochrome P450 2D6 (497 aa, ~56 kDa) is encoded by the human CYP2D6 gene. This protein plays a role in flavoprotein metabolism..", "label": "no"}
{"id": "converted_3587", "sentence1": "Does Estrogen lead to forkhead FoxA1 activation?", "sentence2": "We showed that CTCF acts upstream of the \"pioneer\" factor FOXA1 in determining the genomic response to estrogen. , Almost all ER-chromatin interactions and gene expression changes depended on the presence of FOXA1 and FOXA1 influenced genome-wide chromatin accessibility, FOXA1 is a key determinant of estrogen receptor function and endocrine response., As such, FOXA1 is a major determinant of estrogen-ER activity and endocrine response in breast cancer cells., Location analysis of estrogen receptor alpha target promoters reveals that FOXA1 defines a domain of the estrogen response., Furthermore, knockdown of FoxA1 expression blocks the association of ER with chromatin and estrogen-induced gene expression demonstrating the necessity of FoxA1 in mediating an estrogen response in breast cancer cells., FoxA1 determines estrogen receptor action in breast cancer progression, Given previous findings from cell lines, FoxA1 appears to play a critical role in this reprogramming of ER binding., FOXA1 expression can independently predict chemosensitivity of ER-positive breast cancer patients., FOXA1 expression could be a prognostic marker in ER-positive breast cancer., The pioneer transcription factor FoxA1 plays an important role in estrogen signaling by opening closed chromatin and promoting recruitment of the estrogen receptor to its target regions in DNA, The phosphomimetic FoxA1 promoted the activation of estrogen signaling, whereas the nonphosphorylatable FoxA1 suppressed its activation.[SEP]Relations: estrogen receptor activity has relations: molfunc_protein with GPER1, molfunc_protein with GPER1, molfunc_protein with GPER1, molfunc_protein with GPER1, molfunc_protein with ESR1, molfunc_protein with ESR1, molfunc_protein with ESR1, molfunc_protein with ESR1, molfunc_protein with ESR2, molfunc_protein with ESR2. Definitions: estrogen receptor alpha defined as following: One of the ESTROGEN RECEPTORS that has marked affinity for ESTRADIOL. Its expression and function differs from, and in some ways opposes, ESTROGEN RECEPTOR BETA.. CTCF defined as following: CCN family member 2 (349 aa, ~38kDa) is encoded by the human CCN2 gene. This protein plays a role in the promotion of proliferation and differentiation of chondrocytes and also mediates heparin- and divalent cation-dependent cell adhesion in many different cell types.. FoxA1 defined as following: This gene plays a role in the modulation of gene expression.. estrogen receptor defined as following: Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important.. breast cancer defined as following: A primary or metastatic malignant neoplasm involving the breast. The vast majority of cases are carcinomas arising from the breast parenchyma or the nipple. Malignant breast neoplasms occur more frequently in females than in males.. ER defined as following: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed). domain defined as following: A taxonomic category above that of Kingdom.. 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).. cell lines defined as following: Established cell cultures that have the potential to propagate indefinitely.. FOXA1 defined as following: This gene plays a role in the modulation of gene expression.. chromatin defined as following: The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome. [GOC:elh, PMID:20404130]. Estrogen defined as following: Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds..", "label": "yes"}