tbuckley/cabot-search huggingface dataset:
ACTIVE IMMUNITY TO POLIOMYELITIS IN CHIMPANZEES FOLLOWING SUBCLINICAL INFECTION
Authors: Joseph L. Melnick, Dorothy M. Horstmann
Journal: The Journal of Experimental Medicine (1947)

This report is concerned with the production of subclinical poliomyelitis in the chimpanzee, and immunity to such infection. Subclinical infection was produced in eight chimpanzees by the administration of virus orally or intracutaneously, and was measured by the production of a virus carrier state and the development of neutralizing antibodies. Immunity was tested by attempting to induce the carrier state again by a challenge dose of virus by the same routes. With an homologous strain as the challenge virus, immunity as defined here was produced in each of four chimpanzees tested. Neutralizing antibodies to the homologous strain were present about 1 month following the first exposure to virus by either the oral or cutaneous route. In another group of two chimpanzees, one developed neutralizing antibodies and immunity to heterologous strains, and one did not.
Drug for Colorectal Cancer
Authors: Jr Lester M. Crawford
Journal: JAMA (2002)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Gene Expression Profiles Associated with Response to Chemotherapy in Epithelial Ovarian Cancers
Authors: Amir A. Jazaeri, Christopher S. Awtrey, Gadisetti V.R. Chandramouli, Yao Eric Chuang, Javed Khan, Christos Sotiriou, Olga Aprelikova, Cindy J. Yee, Kristin K. Zorn, Michael J. Birrer, J. Carl Barrett, Jeff Boyd
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The goal of this study was to determine whether distinct gene expression profiles are associated with intrinsic and/or acquired chemoresistance in epithelial ovarian carcinoma. Experimental Design: Gene expression profiles were generated from 21 primary chemosensitive tumors and 24 primary chemoresistant tumors using cDNA-based microarrays. Gene expression profiles of both groups of primary tumors were then compared with those of 15 ovarian carcinomas obtained following platinum-based chemotherapy (“postchemotherapy” tumors). A theme discovery tool was used to identify functional categories of genes involved in drug resistance. Results: Comparison of primary chemosensitive and chemoresistant tumors revealed differential expression of 85 genes (P &amp;lt; 0.001). Comparison of gene expression profiles of primary chemosensitive tumors and postchemotherapy tumors revealed more robust differences with 760 genes differentiating the two groups (P &amp;lt; 0.001). In contrast, only 230 genes were differentially expressed between primary chemoresistant and postchemotherapy groups (P &amp;lt; 0.001). Common to both gene lists were 178 genes representing transcripts differentially expressed between postchemotherapy tumors and all primary tumors irrespective of intrinsic chemosensitivity. The gene expression profile of postchemotherapy tumors compared with that of primary tumors revealed statistically significant overrepresentation of genes encoding extracellular matrix–related proteins. Conclusions: These data show that gene expression profiling can discriminate primary chemoresistant from primary chemosensitive ovarian cancers. Gene expression profiles were also identified that correlate with states of intrinsic and acquired chemoresistance and that represent targets for future investigation and potential therapeutic interventions.
Interaction and sequence diversity among T15 VH genes in CBA/J mice.
Authors: S E Ferguson, S Rudikoff, B A Osborne
Journal: The Journal of Experimental Medicine (1988)

Nucleotide sequences of the four genes composing the T15 heavy chain variable region (VH) family of the CBA/J mouse have been determined. Comparison of these sequences with their published BALB/c and C57BL/10 homologues reveals that nucleotide differences found between given alleles of two strains, i.e., CBA/J and BALB/c, are observed in other family members of the same strain. We suggest that these patterns of sequence variation are most readily explained by gene interaction (conversion). Additionally, the sequence of a CBA/J hybridoma, 6G6, proposed to have been generated by gene conversion, is directly encoded by the CBA/J V11 gene indicating that the putative conversion has occurred meiotically in the germline. These results are consistent with the premise that gene correction is occurring frequently among members of this family and that such processes may contribute significantly to the evolution of Ig variable region genes even in the relatively short time frame of inbred strain derivation.
Vitamin C Further Improves the Protective Effect of Glucagon-Like Peptide-1 on Acute Hypoglycemia-Induced Oxidative Stress, Inflammation, and Endothelial Dysfunction in Type 1 Diabetes
Authors: Antonio Ceriello, Anna Novials, Emilio Ortega, Silvia Canivell, Lucia La Sala, Gemma Pujadas, Loredana Bucciarelli, Maurizio Rondinelli, Stefano Genovese
Journal: Diabetes Care (2013)

OBJECTIVE To test the hypothesis that acute hypoglycemia induces endothelial dysfunction and inflammation through the generation of an oxidative stress. Moreover, to test if the antioxidant vitamin C can further improve the protective effects of glucagon-like peptide 1 (GLP-1) on endothelial dysfunction and inflammation during hypoglycemia in type 1diabetes. RESEARCH DESIGN AND METHODS A total of 20 type 1 diabetic patients underwent four experiments: a period of 2 h of acute hypoglycemia with or without infusion of GLP-1 or vitamin C or both. At baseline, after 1 and 2 h, glycemia, plasma nitrotyrosine, plasma 8-iso prostaglandin F2a (PGF2a), soluble intracellular adhesion molecule-1a (sICAM-1a), interleukin-6 (IL-6), and flow-mediated vasodilation were measured. At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced. RESULTS At 2 h of hypoglycemia, flow-mediated vasodilation significantly decreased, while sICAM-1, 8-iso-PGF2a, nitrotyrosine, and IL-6 significantly increased. The simultaneous infusion of GLP-1 or vitamin C significantly attenuated all of these phenomena. Vitamin C was more effective. When GLP-1 and vitamin C were infused simultaneously, the deleterious effect of hypoglycemia was almost completely counterbalanced. CONCLUSIONS This study shows that vitamin C infusion, during induced acute hypoglycemia, reduces the generation of oxidative stress and inflammation, improving endothelial dysfunction, in type 1 diabetes. Furthermore, the data support a protective effect of GLP-1 during acute hypoglycemia, but also suggest the presence of an endothelial resistance to the action of GLP-1, reasonably mediated by oxidative stress.
Progression of retinopathy after improved metabolic control in type 2 diabetic patients. Relation to IGF-1 and hemostatic variables.
Authors: M Henricsson, K Berntorp, E Berntorp, P Fernlund, G Sundkvist
Journal: Diabetes Care (1999)

OBJECTIVE: To determine the impact of improved glycemic control on the development and progression of retinopathy after the institution of insulin therapy in patients with type 2 diabetes and to assess the relation to IGF-1 and hemostatic variables. RESEARCH DESIGN AND METHODS: In a prospective observational study, 45 type 2 diabetic patients were examined at baseline and 1, 3, 6, 12, and 24 months after change to insulin therapy. Retinopathy was graded on fundus photographs using the Wisconsin scale; HbA1c, IGF-1, and hemostatic variables were measured. RESULTS: During the observation period of 2 years, 23 patients progressed in the retinopathy scale; 8 progressed &amp;gt; or = 3 levels. After 2 years of insulin treatment, HbA1c and IGF-1 were significantly lower than at baseline, whereas the hemostatic variables had not changed significantly. Progression of retinopathy &amp;gt; or = 3 levels was related to the degree of HbA1c reduction, the duration of diabetes, a higher prothrombin fragment 1 + 2 levels (F1 + 2), but not to other hemostatic variables or IGF-1. The relative risk for progression &amp;gt; or = 3 levels was 2.6 when HbA1c had been reduced &amp;gt; or = 3 percent units (95% CI 1.1-6.1). CONCLUSIONS: The magnitude of improvement of HbA1c by the institution of insulin treatment over a 2-year period may be associated with progression of retinopathy in patients with type 2 diabetes.
Cardioprotective Function of the Long Pentraxin PTX3 in Acute Myocardial Infarction
Authors: Monica Salio, Stefano Chimenti, Noeleen De Angelis, Fabiola Molla, Virginia Maina, Manuela Nebuloni, Fabio Pasqualini, Roberto Latini, Cecilia Garlanda, Alberto Mantovani
Journal: Circulation (2008)

Background— Despite widespread clinical use as a prognostic marker in ischemic heart disorders, the actual pathogenetic role of the short pentraxin, C-reactive protein, has not undergone stringent genetic testing because of evolutionary divergence between mouse and humans. The long pentraxin PTX3 is conserved in evolution, is expressed in the heart under inflammatory conditions, and is a candidate prognostic marker in acute myocardial infarction. It was therefore important to assess whether PTX3 plays a pathogenetic role in acute myocardial infarction. Methods and Results— In a model of acute myocardial infarction caused by coronary artery ligation and reperfusion, tissue mRNA expression and circulating levels of PTX3 increased. The interleukin-1R–MyD88 pathway plays a pivotal role in the induction of PTX3 transcript after ischemia. ptx3 -deficient mice showed exacerbated heart damage (33% larger infarcts in null mice; P =0.0047). Increased myocardial damage in ptx3 -deficient mice was associated with a greater no-reflow area, increased neutrophil infiltration, decreased number of capillaries, and increased number of apoptotic cardiomyocytes. In addition, ptx3 -deficient mice with acute myocardial infarction showed higher circulating levels of interleukin-6 and increased C3 deposition in lesional tissue. The phenotype was reversed by exogenous PTX3. Conclusions— Thus, PTX3 plays a nonredundant, regulatory, cardioprotective role in acute myocardial infarction in mice. Our results suggest that modulation of the complement cascade contributes to the cardioprotective function of PTX3.
Triple antiplatelet therapy during percutaneous coronary intervention is associated withimproved outcomes including one-year survival
Authors: Albert W Chan, David J Moliterno, Peter B Berger, Gregg W Stone, Peter M DiBattiste, Steven L Yakubov, Shelly K Sapp, Kathy Wolski, Deepak L Bhatt, Eric J Topol
Journal: Journal of the American College of Cardiology (2003)
Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): a randomised, open-label, blinded-endpoints trial
Authors: Tohru Kobayashi, Tsutomu Saji, Tetsuya Otani, Kazuo Takeuchi, Tetsuya Nakamura, Hirokazu Arakawa, Taichi Kato, Toshiro Hara, Kenji Hamaoka, Shunichi Ogawa, Masaru Miura, Yuichi Nomura, Shigeto Fuse, Fukiko Ichida, Mitsuru Seki, Ryuji Fukazawa, Chitose Ogawa, Kenji Furuno, Hirohide Tokunaga, Shinichi Takatsuki, Shinya Hara, Akihiro Morikawa
Journal: The Lancet (2012)
Force, membrane potential, and [Ca2+]i during activation of rat mesenteric small arteries with norepinephrine, potassium, aluminum fluoride, and phorbol ester. Effects of changes in pHi.
Authors: P E Jensen, A Hughes, H C Boonen, C Aalkjaer
Journal: Circulation Research (1993)

In activated rat mesenteric small arteries, the effect of pHi on force, membrane potential, and free cytosolic calcium ([Ca2+]i) was assessed. Arteries were mounted in a myograph for isometric force development, and [Ca2+]i, pHi, or membrane potential was measured simultaneously with force. During activation with norepinephrine, potassium, aluminum fluoride (AlF-4), and phorbol 12-myristate 13-acetate (PMA, a phorbol ester), the vessels depolarized and [Ca2+]i increased, although the ratio of force to [Ca2+]i was less during potassium activation than with the other types of activation. Changes in pHi, with a constant pHo, were induced with NH4Cl or by changing PCO2. In resting vessels, the effects of the changes in pHi on tension, membrane potential, and [Ca2+]i were negligible. In vessels activated with norepinephrine or AlF-4, alkalinization caused an acute decrease of tone, which could be explained by a decrease in [Ca2+]i consequent to repolarization of the membrane. In vessels activated with potassium or PMA, the effects of alkalinization were smaller. This is consistent with acute alkalinization, affecting steps proximal in the excitation-contraction coupling distal to activation of G proteins. Acidification caused a transient increase in tone and [Ca2+]i, irrespective of the mode of stimulation, without affecting the membrane potential. Ryanodine did not abolish the transient increase in tone and [Ca2+]i. Thus, acute intracellular acidification may induce tone by release of an intracellular ryanodine-insensitive calcium pool or by affecting transmembranal calcium flux although in a membrane potential-independent way.
Antiphospholipid Antibodies: Anticardiolipin and the Lupus Anticoagulant in Systemic Lupus Erythematosus (SLE) and in Non-SLE Disorders
Authors: Paul E. Love
Journal: Annals of Internal Medicine (1990)

Purpose: To determine the prevalence of lupus anticoagulant and anticardiolipin in systemic lupus erythematosus (SLE) and in non-SLE disorders, and to evaluate the clinical significance of these autoantibodies as they relate to thromboembolic events, neuropsychiatric disorders, thrombocytopenia, and fetal loss. Data Identification: A computer-assisted search of the literature (MEDLINE, 1966 to 1989) and review of the bibliographies of all identified articles. Study Selection: Series of ten or more subjects were included if the assays used for detecting lupus anticoagulant or anticardiolipin met the specified minimal criteria for validity. Data Extraction: Series were categorized according to antibody type and underlying disease. A systematic appraisal of patient selection methods, study design, and assay methods was done. Results of Data Analysis: An analysis of 29 published series (comprising over 1000 patients with SLE) yielded an average frequency of 34% for the lupus anticoagulant and 44% for anticardiolipin. Antiphospholipid antibodies are also prevalent in patients with various non-SLE disorders. In patients with SLE, a statistically significant association exists between the presence of either antibody and a history of thrombosis, neurologic disorders, or thrombocytopenia. The available data suggest, but do not firmly support, an association between antiphospholipid antibodies and history of fetal loss in women with SLE. Contrary to prevailing opinion, none of these associations have been shown conclusively in patients with non-SLE disorders. Conclusions: The results of predominantly retrospective series suggest that for certain persons (patients with SLE or closely related disorders) antiphospholipid antibodies may be important risk factors for thrombosis, neurologic disease, thrombocytopenia, and fetal loss. Standardized tests for lupus anticoagulant and anticardiolipin, as well as long-term, prospective clinical studies, are needed to determine the prognostic value of antiphospholipid antibodies.
T cell–derived interleukin (IL)-21 promotes brain injury following stroke in mice
Authors: Benjamin D.S. Clarkson, Changying Ling, Yejie Shi, Melissa G. Harris, Aditya Rayasam, Dandan Sun, M. Shahriar Salamat, Vijay Kuchroo, John D. Lambris, Matyas Sandor, Zsuzsanna Fabry
Journal: The Journal of Experimental Medicine (2014)

T lymphocytes are key contributors to the acute phase of cerebral ischemia reperfusion injury, but the relevant T cell–derived mediators of tissue injury remain unknown. Using a mouse model of transient focal brain ischemia, we report that IL-21 is highly up-regulated in the injured mouse brain after cerebral ischemia. IL-21–deficient mice have smaller infarcts, improved neurological function, and reduced lymphocyte accumulation in the brain within 24 h of reperfusion. Intracellular cytokine staining and adoptive transfer experiments revealed that brain-infiltrating CD4+ T cells are the predominant IL-21 source. Mice treated with decoy IL-21 receptor Fc fusion protein are protected from reperfusion injury. In postmortem human brain tissue, IL-21 localized to perivascular CD4+ T cells in the area surrounding acute stroke lesions, suggesting that IL-21–mediated brain injury may be relevant to human stroke.
Efficacy and Safety of Switching From the DPP-4 Inhibitor Sitagliptin to the Human GLP-1 Analog Liraglutide After 52 Weeks in Metformin-Treated Patients With Type 2 Diabetes
Authors: Richard E. Pratley, Michael A. Nauck, Timothy Bailey, Eduard Montanya, Sebastiano Filetti, Alan J. Garber, Anne B. Thomsen, Sabina Furber, Melanie Davies
Journal: Diabetes Care (2012)

OBJECTIVE To assess the efficacy and safety of switching from sitagliptin to liraglutide in metformin-treated adults with type 2 diabetes. RESEARCH DESIGN AND METHODS In an open-label trial, participants randomized to receive either liraglutide (1.2 or 1.8 mg/day) or sitagliptin (100 mg/day), each added to metformin, continued treatment for 52 weeks. In a 26-week extension, sitagliptin-treated participants were randomly allocated to receive instead liraglutide at either 1.2 or 1.8 mg/day, while participants originally randomized to receive liraglutide continued unchanged. RESULTS Although 52 weeks of sitagliptin changed glycosylated hemoglobin (HbA1c) by −0.9% from baseline, additional decreases occurred after switching to liraglutide (1.2 mg/day, −0.2%, P = 0.006; 1.8 mg/day, −0.5%, P = 0.0001). Conversion to liraglutide was associated with reductions in fasting plasma glucose (FPG) (1.2 mg/day, −0.8 mmol/L, P = 0.0004; 1.8 mg/day, −1.4 mmol/L, P &amp;lt; 0.0001) and body weight (1.2 mg/day, −1.6 kg; 1.8 mg/day, −2.5 kg; both P &amp;lt; 0.0001) and with an increased proportion of patients reaching HbA1c &amp;lt;7% (from ∼30% to ∼50%). Overall treatment satisfaction, assessed by the Diabetes Treatment Satisfaction Questionnaire, improved after switching to liraglutide (pooled 1.2 and 1.8 mg/day, 1.3; P = 0.0189). After switching, mostly transient nausea occurred in 21% of participants, and minor hypoglycemia remained low (3–4% of participants). Continuing liraglutide treatment at 1.2 mg/day and 1.8 mg/day for 78 weeks reduced HbA1c (baseline 8.3 and 8.4%, respectively) by −0.9 and −1.3%, respectively; FPG by −1.3 and −1.7 mmol/L, respectively; and weight by −2.6 and −3.1 kg, respectively, with 9–10% of participants reporting minor hypoglycemia. CONCLUSIONS Glycemic control, weight, and treatment satisfaction improved after switching from sitagliptin to liraglutide, albeit with a transient increase in gastrointestinal reactions.
Physical exercise and executive functions in preadolescent children, adolescents and young adults: a meta-analysis
Authors: Lot Verburgh, Marsh Königs, Erik J A Scherder, Jaap Oosterlaan
Journal: British Journal of Sports Medicine (2013)

Purpose The goal of this meta-analysis was to aggregate available empirical studies on the effects of physical exercise on executive functions in preadolescent children (6–12 years of age), adolescents (13–17 years of age) and young adults (18–35 years of age). Method The electronic databases PubMed, EMBASE and SPORTDiscus were searched for relevant studies reporting on the effects of physical exercise on executive functions. Nineteen studies were selected. Results There was a significant overall effect of acute physical exercise on executive functions (d=0.52, 95% CI 0.29 to 0.76, p&lt;0.001). There were no significant differences between the three age groups (Q (2)=0.13, p=0.94). Furthermore, no significant overall effect of chronic physical exercise (d=0.14, 95%CI −0.04 to 0.32, p=0.19) on executive functions (Q (1)=5.08, p&lt;0.05) was found. Meta-analytic effect sizes were calculated for the effects of acute physical exercise on the domain's inhibition/interference control (d=0.46, 95% CI 0.33 to 0.60, p&lt;0.001) and working memory (d=0.05, 95% CI −0.51 to 0.61, p=0.86) as well as for the effects of chronic physical exercise on planning (d=0.16, 95% CI 0.18 to 0.89, p=0.18). Conclusions Results suggest that acute physical exercise enhances executive functioning. The number of studies on chronic physical exercise is limited and it should be investigated whether chronic physical exercise shows effects on executive functions comparable to acute physical exercise. This is highly relevant in preadolescent children and adolescents, given the importance of well-developed executive functions for daily life functioning and the current increase in sedentary behaviour in these age groups.
Preferred analysis methods for Affymetrix GeneChips revealed by a wholly defined control dataset
Authors: Sung E Choe, Michael Boutros, Alan D Michelson, George McDonald Church, Marc S Halfon
Journal: Genome biology (2005)

Abstract Background As more methods are developed to analyze RNA-profiling data, assessing their performance using control datasets becomes increasingly important. Results We present a 'spike-in' experiment for Affymetrix GeneChips that provides a defined dataset of 3,860 RNA species, which we use to evaluate analysis options for identifying differentially expressed genes. The experimental design incorporates two novel features. First, to obtain accurate estimates of false-positive and false-negative rates, 100-200 RNAs are spiked in at each fold-change level of interest, ranging from 1.2 to 4-fold. Second, instead of using an uncharacterized background RNA sample, a set of 2,551 RNA species is used as the constant (1x) set, allowing us to know whether any given probe set is truly present or absent. Application of a large number of analysis methods to this dataset reveals clear variation in their ability to identify differentially expressed genes. False-negative and false-positive rates are minimized when the following options are chosen: subtracting nonspecific signal from the PM probe intensities; performing an intensity-dependent normalization at the probe set level; and incorporating a signal intensity-dependent standard deviation in the test statistic. Conclusions A best-route combination of analysis methods is presented that allows detection of approximately 70% of true positives before reaching a 10% false-discovery rate. We highlight areas in need of improvement, including better estimate of false-discovery rates and decreased false-negative rates.