tbuckley/cabot-search huggingface dataset:
Integration of Cell Line and Clinical Trial Genome-Wide Analyses Supports a Polygenic Architecture of Paclitaxel-Induced Sensory Peripheral Neuropathy
Authors: Heather E. Wheeler, Eric R. Gamazon, Claudia Wing, Uchenna O. Njiaju, Chidiamara Njoku, Robert Michael Baldwin, Kouros Owzar, Chen Jiang, Dorothy Watson, Ivo Shterev, Michiaki Kubo, Hitoshi Zembutsu, Eric P. Winer, Clifford A. Hudis, Lawrence N. Shulman, Yusuke Nakamura, Mark J. Ratain, Deanna L. Kroetz, Nancy J. Cox, Mary Eileen Dolan
Journal: Clinical Cancer Research (2012)

We sought to show the relevance of a lymphoblastoid cell line (LCL) model in the discovery of clinically relevant genetic variants affecting chemotherapeutic response by comparing LCL genome-wide association study (GWAS) results to clinical GWAS results.A GWAS of paclitaxel-induced cytotoxicity was conducted in 247 LCLs from the HapMap Project and compared with a GWAS of sensory peripheral neuropathy in patients with breast cancer (n = 855) treated with paclitaxel in the Cancer and Leukemia Group B (CALGB) 40101 trial. Significant enrichment was assessed by permutation resampling analysis.We observed an enrichment of LCL cytotoxicity-associated single-nucleotide polymorphisms (SNP) in the sensory peripheral neuropathy-associated SNPs from the clinical trial with concordant allelic directions of effect (empirical P = 0.007). Of the 24 SNPs that overlap between the clinical trial (P < 0.05) and the preclinical cytotoxicity study (P < 0.001), 19 of them are expression quantitative trait loci (eQTL), which is a significant enrichment of this functional class (empirical P = 0.0447). One of these eQTLs is located in RFX2, which encodes a member of the DNA-binding regulatory factor X family. Decreased expression of this gene by siRNA resulted in increased sensitivity of Neuroscreen-1(NS-1; rat pheochromocytoma) cells to paclitaxel as measured by reduced neurite outgrowth and increased cytotoxicity, functionally validating the involvement of RFX2 in nerve cell response to paclitaxel.The enrichment results and functional example imply that cellular models of chemotherapeutic toxicity may capture components of the underlying polygenic architecture of related traits in patients.
Randomized, Placebo-Controlled, Phase III Trial of Yeast-Derived Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Versus Peptide Vaccination Versus GM-CSF Plus Peptide Vaccination Versus Placebo in Patients With No Evidence of Disease After Complete Surgical Resection of Locally Advanced and/or Stage IV Melanoma: A Trial of the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group (E4697)
Authors: David H. Lawson, Sandra Lee, Fengmin Zhao, Ahmad A. Tarhini, Kim A. Margolin, Marc S. Ernstoff, Michael B. Atkins, Gary I. Cohen, Theresa L. Whiteside, Lisa H. Butterfield, John M. Kirkwood
Journal: Journal of Clinical Oncology (2015)

We conducted a double-blind, placebo-controlled trial to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) and peptide vaccination (PV) on relapse-free survival (RFS) and overall survival (OS) in patients with resected high-risk melanoma.
Endotoxin: does it have a role in prevention of lung cancer
Authors: J H Lange
Journal: Thorax (2003)

The paper by Drs Douwes, Pearce and Heederik provides an interesting overview of how endotoxin may interact in atopy and asthma. It discusses issues as to whether endotoxin plays a role in prevention of atopy and asthma or may, in fact, be a contributor to these respiratory diseases. However, readers should be aware that there is another important issue, although controversial, related to endotoxin and the lung—that is, …
Chronic juvenile toxic epidemic syndrome.
Authors: M Izquierdo, I Mateo, M Rodrigo, C Mena, M Sebastian, J Conde, J J Gomez-Reino
Journal: Annals of the Rheumatic Diseases (1985)

The clinical manifestations in 21 children with chronic toxic epidemic syndrome (TES) and musculoskeletal manifestations were analysed and compared with those of the adult population. The sex ratio (2.5:1, F/M) was different from the one found in adults (6:1, F/M). The neuromuscular syndrome, the scleroderma-like picture, the pulmonary hypertension, and the Raynaud9s phenomenon characteristic of TES were similar to those in adults but milder in children. The less severe vascular endothelial lesions found on microscopic examination might explain the better prognosis in this age group.
Age of menarche in various categories of Indian sportswomen.
Authors: L. S. Sidhu, R. Grewal
Journal: British Journal of Sports Medicine (1980)

Data on the age of menarche has been collected on 264 Indian sportswomen, and 108 girls forming the control group, all hailing from the Punjab, Haryana, chandigarh and Delhi. Outstanding athletes and players of hockey, basketball and volleyball were included. The combined mean age at menarche for sportswomen is 15.21 years and for the control sample is 14.05 years. The differences in the two series are statistically significant. The mean age at menarche in hockey, basketball, volleyball and athletes is found to be 15.15, 15.40, 15.05 and 15.27 years respectively. The differences in these groups, however, are not found to be statistically significant.
Alveolar Surfactant Homeostasis and the Pathogenesis of Pulmonary Disease
Authors: Jeffrey A. Whitsett, Susan E. Wert, Timothy E. Weaver
Journal: Annual Review of Medicine (2010)

The alveolar region of the lung creates an extensive epithelial surface that mediates the transfer of oxygen and carbon dioxide required for respiration after birth. Maintenance of pulmonary function depends on the function of type II epithelial cells that synthesize and secrete pulmonary surfactant lipids and proteins, reducing the collapsing forces created at the air-liquid interface in the alveoli. Genetic and acquired disorders associated with the surfactant system cause both acute and chronic lung disease. Mutations in the ABCA3, SFTPA, SFTPB, SFTPC, SCL34A2, and TERT genes disrupt type II cell function and/or surfactant homeostasis, causing neonatal respiratory failure and chronic interstitial lung disease. Defects in GM-CSF receptor function disrupt surfactant clearance, causing pulmonary alveolar proteinosis. Abnormalities in the surfactant system and disruption of type II cell homeostasis underlie the pathogenesis of pulmonary disorders previously considered idiopathic, providing the basis for improved diagnosis and therapies of these rare lung diseases.
Look-back study of infectivity of anti-HCV ELISA-positive blood components
Authors: H. Vrielink, C.L. van der Poel, H.W. Reesink, E. Scholten, H.W. Reesink, H.L. Zaaijer, H.T.M. Cuypers, P.N. Lelie, L.C.M. Kremer, M.H.J. van Oera
Journal: The Lancet (1995)
Telbivudine or lamivudine use in late pregnancy safely reduces perinatal transmission of hepatitis B virus in real‐life practice
Authors: Hua Zhang, Calvin Q. Pan, Qiumei Pang, Ruihua Tian, Miaoe Yan, Xin Liu
Journal: Hepatology (2014)

Little observational data exist describing telbivudine (LdT) or lamivudine (LAM) use in late pregnancy for preventing hepatitis B mother-to-child transmission (MTCT) in real-world settings. During the period of January 2009 to March 2011, we enrolled hepatitis B e antigen-positive mothers with HBV DNA >6 log10 copies/mL in China. At gestation week 28, the mothers received LdT or LAM until postpartum week 4 or no treatment (NTx). The study endpoints were the safety of LdT/LAM use and MTCT rates. Of the 700 mothers enrolled, 648 (LdT/LAM/NTx=252/51/345) completed the 52-week study with 661 infants (LdT/LAM/NTx=257/52/352). On treatment, viral rebound occurred in 1.6% of mothers, all resulting from medication noncompliance. There was no genotypic mutation detected. At delivery, significantly lower HBV DNA levels were noted in mothers who received LdT or LAM versus NTx. Alanine aminotransferase flares were observed in 17.1% of treated mothers versus 6.3% of untreated mothers (P < 0.001). At birth, hepatitis B surface antigen (HBsAg) was detected in 20% and 24% of newborns in the treated and NTx groups, respectively. At week 52, an intention-to-treat analysis indicated 2.2% (95% confidence [CI]: 0.6-3.8) of HBsAg+ infants from the treated group versus 7.6% (95% CI: 4.9-10.3) in the NTx group (P50.001) and no difference of HBsAg+ rate between infants in the LdT and LAM groups(1.9% vs. 3.7%; P=0.758). On-treatment analysis indicated 0% of HBsAg+ infants in the treated group versus 2.84% in the NTx group (P=0.002). There were no differences for gestational age or infants' height, weight, Apgar scores, or birth defect rates between infants from the treated and untreated groups. LdT and LAM use in late pregnancy for highly viremic mothers was equally effective in reducing MTCT. The treatment was well tolerated with no safety concerns identified.
Superiority of Fluorodeoxyglucose Positron Emission Tomography to Other Functional Imaging Techniques in the Evaluation of Metastatic <i>SDHB</i>-Associated Pheochromocytoma and Paraganglioma
Authors: Henri J.L.M. Timmers, Anna Kozupa, Clara C. Chen, Jorge A. Carrasquillo, Alexander Ling, Graeme Eisenhofer, Karen T. Adams, Daniel Solis, Jacques W.M. Lenders, Karel Pacak
Journal: Journal of Clinical Oncology (2007)

Purpose Germline mutations of the gene encoding subunit B of the mitochondrial enzyme succinate dehydrogenase (SDHB) predispose to malignant paraganglioma (PGL). Timely and accurate localization of these aggressive tumors is critical for guiding optimal treatment. Our aim is to evaluate the performance of functional imaging modalities in the detection of metastatic lesions of SDHB-associated PGL. Patients and Methods Sensitivities for the detection of metastases were compared between [ 18 F]fluorodopamine ([ 18 F]FDA) and [ 18 F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET), iodine-123- ( 123 I) and iodine-131 ( 131 I) -metaiodobenzylguanidine (MIBG), 111 In-pentetreotide, and Tc-99m-methylene diphosphonate bone scintigraphy in 30 patients with SDHB-associated PGL. Computed tomography (CT) and magnetic resonance imaging (MRI) served as standards of reference. Results Twenty-nine of 30 patients had metastatic lesions. In two patients, obvious metastatic lesions on functional imaging were missed by CT and MRI. Sensitivity according to patient/body region was 80%/65% for 123 I-MIBG and 88%/70% for [ 18 F]FDA-PET. False-negative results on 123 I-MIBG scintigraphy and/or [ 18 F]FDA-PET were not predicted by genotype or biochemical phenotype. [ 18 F]FDG-PET yielded a by patient/by body region sensitivity of 100%/97%. At least 90% of regions that were false negative on 123 I-MIBG scintigraphy or [ 18 F]FDA-PET were detected by [ 18 F]FDG-PET. In two patients, 111 In-pentetreotide scintigraphy detected liver lesions that were negative on other functional imaging modalities. Sensitivities were similar before and after chemotherapy or 131 I-MIBG treatment, except for a trend toward lower post- (60%/41%) versus pretreatment (80%/65%) sensitivity of 123 I-MIBG scintigraphy. Conclusion With a sensitivity approaching 100%, [ 18 F]FDG-PET is the preferred functional imaging modality for staging and treatment monitoring of SDHB-related metastatic PGL.
Neutrophil-specific granule deficiency: homozygous recessive inheritance of a frameshift mutation in the gene encoding transcription factor CCAAT/enhancer binding protein–ε
Authors: Adrian F. Gombart, Masaaki Shiohara, Scott H. Kwok, Kazunaga Agematsu, Atsushi Komiyama, H. Phillip Koeffler
Journal: Blood (2001)
From the Institute of Medicine
Authors: M. Pechura
Journal: JAMA (1993)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
709 IDENTIFICATION OF PREDICTING FACTORS FOR SEROCONVERSION OF HEPATITIS B E ANTIGEN WITHIN A YEAR AMONG BIOCHEMICAL, PATHOLOGICAL AND VIROLOGICAL MARKERS
Authors: S.K. Bae, H. Yatsuhashi, K. Yano, M. Fukuda, R. Nakao, R. Hamada, S. Hashimoto, A. Nishikawa, Y. Motoyoshi, S. Nagaoka, K. Yanagi, S. Abiru, A. Komori, H. Ishibashi, M. Ito
Journal: Journal of Hepatology (2010)
Phenotypic and transcriptional response to selection for alcohol sensitivity in Drosophila melanogaster
Authors: Tatiana V Morozova, Robert RH Anholt, Trudy FC Mackay
Journal: Genome biology (2007)

Abstract Background Alcoholism is a complex disorder determined by interactions between genetic and environmental risk factors. Drosophila represents a powerful model system to dissect the genetic architecture of alcohol sensitivity, as large numbers of flies can readily be reared in defined genetic backgrounds and under controlled environmental conditions. Furthermore, flies exposed to ethanol undergo physiological and behavioral changes that resemble human alcohol intoxication, including loss of postural control, sedation, and development of tolerance. Results We performed artificial selection for alcohol sensitivity for 35 generations and created duplicate selection lines that are either highly sensitive or resistant to ethanol exposure along with unselected control lines. We used whole genome expression analysis to identify 1,678 probe sets with different expression levels between the divergent lines, pooled across replicates, at a false discovery rate of q &lt; 0.001. We assessed to what extent genes with altered transcriptional regulation might be causally associated with ethanol sensitivity by measuring alcohol sensitivity of 37 co-isogenic P -element insertional mutations in 35 candidate genes, and found that 32 of these mutants differed in sensitivity to ethanol exposure from their co-isogenic controls. Furthermore, 23 of these novel genes have human orthologues. Conclusion Combining whole genome expression profiling with selection for genetically divergent lines is an effective approach for identifying candidate genes that affect complex traits, such as alcohol sensitivity. Because of evolutionary conservation of function, it is likely that human orthologues of genes affecting alcohol sensitivity in Drosophila may contribute to alcohol-associated phenotypes in humans.
Immune system control of rat and rabbit colonic electrolyte transport. Role of prostaglandins and enteric nervous system.
Authors: M J Bern, C W Sturbaum, S S Karayalcin, H M Berschneider, J T Wachsman, D W Powell
Journal: Journal of Clinical Investigation (1989)

The role of the immune system in controlling intestinal electrolyte transport was studied in rat and rabbit colon in Ussing chambers. A phagocyte stimulus, the chemotactic peptide FMLP, and a mast cell stimulus, sheep anti-rat IgE, caused a brief (less than 10 min) increase in short-circuit current (Isc). Products of immune system activation, platelet-activating factor (PAF) and reactive oxygen species (ROS), caused a sustained, biphasic increase in the Isc. Ion replacement and flux studies indicated that these agonists stimulated electrogenic Cl secretion and inhibited neutral NaCl absorption; responses that were variably inhibited by the cyclooxygenase blockers indomethacin and piroxicam. Lesser degrees of inhibition by nordihydroguaiaretic acid could be accounted for by decreased prostaglandin synthesis rather than by lipoxygenase blockade. Tetrodotoxin, hexamethonium, and atropine also inhibited immune agonist-stimulated Isc, but had no effect on immune agonist-stimulated production of PGE2 or PGI2. These results indicate that immune system agonists alter intestinal epithelial electrolyte transport through release of cyclooxygenase products from cells in the lamina propria with at least 50% of the response being due to cyclooxygenase product activation of the enteric nervous system. The immune system, like the enteric nervous system and the endocrine system, may be a major regulating system for intestinal water and electrolyte transport in health and disease.
Adjuvant chemoendocrine therapy in postmenopausal breast cancer: cyclophosphamide, methotrexate, and fluorouracil dose and schedule may make a difference. International Breast Cancer Study Group.
Authors: A Goldhirsch, A S Coates, M Colleoni, M Castiglione-Gertsch, R D Gelber
Journal: Journal of Clinical Oncology (1998)

PURPOSE Adjuvant cytotoxics prolong disease-free survival (DFS) and overall survival (OS) in patients with operable breast cancer. The first reported effective adjuvant combination regimen consisted of oral cyclophosphamide on days 1 to 14 with intravenous methotrexate and fluorouracil on days 1 and 8, repeated every 28 days (classical CMF). These drugs have since been extensively used with or without endocrine therapies and/or other cytotoxic agents. Although doses and schedules have varied widely, the combination of these three drugs is generically referred to as CMF. RESULTS Reducing the dose and/or altering the schedule of CMF have compromised its efficacy in metastatic breast cancer. Reduction below standard dose of a similar regimen also gave inferior results in the adjuvant setting. CONCLUSION Details of dose and schedule may therefore explain part of the heterogeneity of results observed with CMF. Particular controversy surrounds the contribution of CMF in postmenopausal women who are also receiving tamoxifen (TAM). However, the trials that demonstrated a significant benefit for the addition of CMF to TAM, even in postmenopausal women with estrogen receptor-positive tumors, used classical CMF. Therefore, adherence to the classical dose and schedule is recommended when CMF is used in adjuvant therapy.
Aging-Dependent Demethylation of Regulatory Elements Correlates with Chromatin State and Improved β Cell Function
Authors: Dana Avrahami, Changhong Li, Jia Zhang, Jonathan Schug, Ran Avrahami, Shilpa Rao, Michael B. Stadler, Lukas Burger, Dirk Schübeler, Benjamin Glaser, Klaus H. Kaestner
Journal: Cell Metabolism (2015)
Vav3 Modulates B Cell Receptor Responses by Regulating Phosphoinositide 3-Kinase Activation
Authors: Kazunori Inabe, Masamichi Ishiai, Andrew M. Scharenberg, Norman Freshney, Julian Downward, Tomohiro Kurosaki
Journal: The Journal of Experimental Medicine (2002)

To elucidate the mechanism(s) by which Vav3, a new member of the Vav family proteins, participates in B cell antigen receptor (BCR) signaling, we have generated a B cell line deficient in Vav3. Here we report that Vav3 influences phosphoinositide 3-kinase (PI3K) function through Rac1 in that phosphatidylinositol-3,4,5-trisphosphate (PIP3) generation was attenuated by loss of Vav3 or by expression of a dominant negative form of Rac1. The functional interaction between PI3K and Rac1 was also demonstrated by increased PI3K activity in the presence of GTP-bound Rac1. In addition, we show that defects of calcium mobilization and c-Jun NH2-terminal kinase (JNK) activation in Vav3-deficient cells are relieved by deletion of a PIP3 hydrolyzing enzyme, SH2 domain-containing inositol polyphosphate 5′-phosphatase (SHIP). Hence, our results suggest a role for Vav3 in regulating the B cell responses by promoting the sustained production of PIP3 and thereby calcium flux.
Identification of an Adenylyl Cyclase Inhibitor for Treating Neuropathic and Inflammatory Pain
Authors: Hansen Wang, Hui Xu, Long-Jun Wu, Susan S. Kim, Tao Chen, Kohei Koga, Giannina Descalzi, Bo Gong, Kunjumon I. Vadakkan, Xuehan Zhang, Bong-Kiun Kaang, Min Zhuo
Journal: Science Translational Medicine (2011)

In animal models, an adenylyl cyclase 1 inhibitor acts as an effective treatment for neuropathic pain, in part by acting on the anterior cingulate cortex.
Safety and efficacy of allogeneic umbilical cord red blood cell transfusion for children with severe anaemia in a Kenyan hospital: an open-label single-arm trial
Authors: Oliver W Hassall, Johnstone Thitiri, Greg Fegan, Fauzat Hamid, Salim Mwarumba, Douglas Denje, Kongo Wambua, Kishor Mandaliya, Kathryn Maitland, Imelda Bates
Journal: The Lancet Haematology (2015)

Background In sub-Saharan Africa, children are frequently admitted with severe anaemia needing an urgent blood transfusion, but blood is often unavailable.When conventional blood supplies are inadequate, allogeneic umbilical cord blood could be a feasible alternative.The aim of this study was to assess the safety and effi cacy of cord blood transfusion in children with severe anaemia.Methods Between June 26, 2007, and May 20, 2008, 413 children needing an urgent blood transfusion were admitted to Kilifi District Hospital in Kenya.Of these, 87 children were eligible for our study-ie, younger than 12 years, no signs of critical illness, and haemoglobin 100 g/L or lower (if aged 3 months or younger) or 40 g/L or lower (if older than 3 months).Cord blood was donated at Coast Provincial General Hospital, Mombasa, and screened for transfusion-transmitted infections and bacterial contamination.Red blood cells were stored vertically at 2-6°C to enable sedimentation.After transfusion, children were monitored closely for adverse events and followed up for 28 days.The primary outcome measure was the frequency and nature of adverse reactions associated with the transfusion.Secondary outcomes were the changes in haemoglobin concentrations 24 h and 28 days after transfusion, compared with pretransfusion levels.This trial is registered on ISRCTN.com,number ISRCTN66687527.Findings Of the 87 children eligible for the study, cord blood was unavailable for 24, six caregivers declined consent, and two children were withdrawn before transfusion.Therefore, 55 children received umbilical cord red blood cells from 74 donations.Ten (18%) children had ten serious adverse events and 43 (78%) had 94 adverse events; the most frequent adverse events were anaemia (n=14), weight loss (n=12), and vomiting (n=10).An independent expert panel judged none of these adverse events to be probably or certainly caused by the cord blood transfusion (one-sided 97•5% CI 0-6•5).Haemoglobin increased by a median of 26 g/L (IQR 21-31) 24 h after transfusion and by 50 g/L (10-68) a median of 29 days (28-35) after transfusion.Interpretation These preliminary data suggest that cord blood could be an important supplementary source of blood for transfusion in children in sub-Saharan Africa.Further studies are needed to compare the safety and effi cacy of cord blood with conventional adult-donated blood for transfusions.Challenges associated with cost, infrastructure, and scale up also need investigating.
Chronic lymphocytic leukemias utilizing the VH3-21 gene display highly restricted Vλ2-14 gene use and homologous CDR3s: implicating recognition of a common antigen epitope
Authors: Gerard Tobin, Ulf Thunberg, Anna Johnson, Inger Eriksson, Ola Söderberg, Karin Karlsson, Mats Merup, Gunnar Juliusson, Juhani Vilpo, Gunilla Enblad, Christer Sundström, Göran Roos, Richard Rosenquist
Journal: Blood (2003)