tbuckley/cabot-search huggingface dataset:
Peroxisome proliferator–activated receptor (PPAR)α expression in T cells mediates gender differences in development of T cell–mediated autoimmunity
Authors: Shannon E. Dunn, Shalina S. Ousman, Raymond A. Sobel, Luis Zuniga, Sergio E. Baranzini, Sawsan Youssef, Andrea Crowell, John Loh, Jorge Oksenberg, Lawrence Steinman
Journal: The Journal of Experimental Medicine (2007)

Peroxisome proliferator–activated receptor (PPAR)α is a nuclear receptor that mediates gender differences in lipid metabolism. PPARα also functions to control inflammatory responses by repressing the activity of nuclear factor κB (NF-κB) and c-jun in immune cells. Because PPARα is situated at the crossroads of gender and immune regulation, we hypothesized that this gene may mediate sex differences in the development of T cell–mediated autoimmune disease. We show that PPARα is more abundant in male as compared with female CD4+ cells and that its expression is sensitive to androgen levels. Genetic ablation of this gene selectively removed the brake on NF-κB and c-jun activity in male T lymphocytes, resulting in higher production of interferon γ and tumor necrosis factor (but not interleukin 17), and lower production of T helper (Th)2 cytokines. Upon induction of experimental autoimmune encephalomyelitis, male but not female PPARα−/− mice developed more severe clinical signs that were restricted to the acute phase of disease. These results suggest that males are less prone to develop Th1-mediated autoimmunity because they have higher T cell expression of PPARα.
Science and Society: Fifty Years Later—The 2014 Presidential Address
Authors: Clifford A. Hudis
Journal: Journal of Clinical Oncology (2014)

s and 34,000 attendees. The theme for this year’s meeting is “Science and Society,” chosen to emphasize my intention to help bring our scientific community and the society we serve closer together so that we can more quickly make our world free from the fear of cancer. I chose to begin with and to emphasize the word “intention” because I believe that this word can sharpen our focus, clarify our vision, and help us marshal the resources we need to achieve our goals. And the power of intention is as relevant to us as it was to our founders 50 years ago. Reflecting on societal events leading up to ASCO’s founding, I was quickly drawn to a clip of President John F. Kennedy speaking at Rice University in 1962. The phrase that resonates for me is, “One which we intend to win.” His emphasis on intention resonates because it is both optimistic and energizing, but it is also humble and effective. And it was JFK’s clarity of intention that galvanized our successful efforts to reach the moon within 7
Obituary Listing
Authors: Mary Vest Mason
Journal: JAMA (1998)

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
A neuraminidase from Trypanosoma cruzi removes sialic acid from the surface of mammalian myocardial and endothelial cells.
Authors: P Libby, J Alroy, M E Pereira
Journal: Journal of Clinical Investigation (1986)

Trypanosoma cruzi causes Chagasic heart disease, a major public health problem in Latin America. The mechanism of interaction of this protozooan parasite with host cells is poorly understood. We recently found that the infective trypomastigote form a T. cruzi exhibits neuraminidase activity and can desialylate mammalian erythrocytes. However, it is not known if T. cruzi can also modify the surfaces of cardiovascular cells that are directly involved in the most important clinical manifestations of this disease. Accordingly, this study determined whether T. cruzi can remove sialic acid from cultured rat myocardial or human vascular endothelial cells. Sialic acid was labeled metabolically with the precursor 3H-N-acetyl-D-mannosamine. Soluble neuraminidase, isolated from intact T. cruzi trypomastigotes, caused significant release of labeled material from myocardial cells (e.g., 2,174 +/- 27 dpm/h vs. spontaneous release of 306 +/- 30 dpm/h, n = 4, P less than 0.001). Chromatographic analysis showed that the bulk of the radioactivity released by T. cruzi neuraminidase was sialic acid. Intact T. cruzi trypomastigotes also released sialic acid from metabolically labeled myocardial cells in a concentration-dependent manner. In contrast, a noninfective form of T. cruzi, the amastigote, did not desialylate these cells. Galactose oxidase labeling demonstrated newly desialylated glycoproteins on the surface of myocardial cells treated with T. cruzi neuraminidase. Desialylation of myocardial cells was confirmed histochemically by the appearance of binding sites for peanut agglutinin, a lectin that binds to complex oligosaccharide moieties after removal of the terminal sialyl residue. T. cruzi neuraminidase also removed sialic acid from adult human saphenous vein endothelial cells, as determined by both histochemical and metabolic labeling studies. Thus, infective forms of T. cruzi can chemically modify the surfaces of myocardial and vascular endothelial cells by desialylation. This alteration may play a role in the initial interaction of this parasite with these important target cells of the host cardiovascular system.
Transfer of Chloroplast Genomic DNA to Mitochondrial Genome Occurred At Least 300 MYA
Authors: Daryi Wang, Yu-Wei Wu, Arthur Chun-Chieh Shih, Chung-Shien Wu, Ya-Nan Wang, Shu-Miaw Chaw
Journal: Molecular Biology and Evolution (2007)

With the completion of the first gymnosperm mitochondrial genome (mtDNA) from Cycas taitungensis and the availability of more mtDNA taxa in the past 5 years, we have conducted a systematic analysis of DNA transfer from chloroplast genomes (cpDNAs) to mtDNAs (mtpts) in 11 plants, including 2 algae, 1 liverwort, 1 moss, 1 gymnosperm, 3 monocots, and 3 eudicots. By using shared gene order and boundaries between different mtpts as the criterion, the timing of cpDNA transfer during plant evolution was estimated from the phylogenetic tree reconstructed independently from concatenated protein-coding genes of 11 available mtDNAs. Several interesting findings emerged. First, frequent DNA transfer from cpDNA to mtDNA occurred at least as far back as the common ancestor of extant gymnosperms and angiosperms, about 300 MYA. The oldest mtpt is trnV(uac)-trnM(cau)-atpE-atpB-rbcL. Three other mtpts--psaA-psaB, rps19-trnH(gug)-rpl2-rpl23, and psbE-psbF--were dated to the common ancestor of extant angiosperms, at least 150 MYA. However, all protein-coding genes of mtpts have degenerated since their first transfer. Therefore, mtpts contribute nothing to the functioning of mtDNA but junk sequences. We discovered that the cpDNA transfers have occurred randomly at any positions of the cpDNAs. We provide strong evidence that the cp-derived tRNA-trnM(cau) is the only mtpt (1 out of 3 cp-derived tRNA shared by seed plants) truly transferred from cpDNA to mtDNA since the time of the common ancestor of extant gymnosperms and angiosperms. Our observations support the proposition of Richly and Leister (2004) that "primary insertions of organellar DNAs are large and then diverge and fragment over evolutionary time."
Transient outward current modulates discontinuous conduction in rabbit ventricular cell pairs
Authors: D Huelsing
Journal: Cardiovascular Research (2001)

Objective: While several studies have demonstrated that the L-type calcium current maintains discontinuous conduction, the contribution of the transient outward current (Ito) to conduction remains unclear. This study evaluated the effects of Ito inhibition on conduction between ventricular myocytes. Methods: An electronic circuit with a variable resistance (Rj) was used to electrically couple single epicardial myocytes isolated from rabbit right ventricle. We inhibited Ito with 4-aminopyridine superfusion, rate–acceleration, or premature stimulation to evaluate the subsequent effects on conduction delay and the critical Rj, which was quantified as the highest Rj that could be imposed before conduction failed. Results:Ito inhibition significantly enhanced conduction in all cell pairs (n = 23). Pharmacologic inhibition of Ito resulted in a 32±5% decrease in conduction delay and a 36±7% increase in critical Rj. Similarly, reduction of the basic cycle length from 2 to 0.5 s resulted in a 31±3% decrease in conduction delay and a 31±3% increase in critical Rj. Finally, premature action potentials conducted with a 41±4% shorter conduction delay and a 73±24% higher critical Rj than basic action potentials. Conclusions:Ito inhibition significantly enhanced conduction across high Rj. These results suggest Ito may contribute to rate-dependent conduction abnormalities.
A rapid method to map mutations in Drosophila
Authors: Sophie G Martin, Krista C Dobi, Daniel St Johnston
Journal: Genome biology (2001)

Genetic screens in Drosophila have provided a wealth of information about a variety of cellular and developmental processes. It is now possible to screen for mutant phenotypes in virtually any cell at any stage of development by performing clonal screens using the flp/FRT system. The rate-limiting step in the analysis of these mutants is often the identification of the mutated gene, however, because traditional mapping strategies rely mainly on genetic and cytological markers that are not easily linked to the molecular map.Here we describe the development of a single-nucleotide polymorphism (SNP) map for chromosome arm 3R. The map contains 73 polymorphisms between the standard FRT chromosome, and a mapping chromosome that carries several visible markers (rucuca), at an average density of one SNP per 370 kilobases (kb). Using this collection, we show that mutants can be mapped to a 400 kb interval in a single meiotic mapping cross, with only a few hundred SNP detection reactions. Discovery of further SNPs in the region of interest allows the mutation to be mapped with the same recombinants to a region of about 50 kb.The combined use of standard visible markers and molecular polymorphisms in a single mapping strategy greatly reduces both the time and cost of mapping mutations, because it requires at least four times fewer SNP detection reactions than a standard approach. The use of this map, or others developed along the same lines, will greatly facilitate the identification of the molecular lesions in mutants from clonal screens.
MacIntosh arthroplasty for the rheumatoid knee: a 10-year follow up.
Authors: B P Wordsworth, D T Shakespeare, A G Mowat
Journal: Annals of the Rheumatic Diseases (1985)

The results of 75 MacIntosh arthroplasties performed for rheumatoid arthritis of the knee in 63 patients were reviewed at least 10 years after surgery. Forty-two knees in 35 patients were available for assessment. Eleven arthroplasties had been revised to total knee replacement without difficulty because of pain or poor function. The remaining 31 knees in 25 patients gave good or excellent results in 22 cases, fair in eight, and poor in one. Seven patients could not be traced, and 21 patients representing 26 knees had died. At least half these knees had given satisfactory results immediately before death judged by review of the case notes. The difficulty of comparing functional status with the preoperative state because of progressive multiarticular disease was highlighted. Although greater angular deformities preoperatively reduced the chance of success in the medium term, late failure of the arthroplasty after five years was very rare. Approximately two-thirds of all the arthroplasties performed gave satisfactory results at 10-year follow up or until the time of death.
What can experience add to early medical education? Consensus survey
Authors: Tim Dornan, Chris Bundy
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To provide a rationale for integrating experience into early medical education ("early experience"). <b>Design</b> Small group discussions to obtain stakeholders9 views. Grounded theory analysis with respondent, internal, and external validation. <b>Setting</b> Problem based, undergraduate medical curriculum that is not vertically integrated. <b>Participants</b> A purposive sample of 64 students, staff, and curriculum leaders from three university medical schools in the United Kingdom. <b>Results</b> Without early experience, the curriculum was socially isolating and divorced from clinical practice. The abruptness of students9 transition to the clinical environment in year 3 generated positive and negative emotions. The rationale for early experience would be to ease the transition; orientate the curriculum towards the social context of practice; make students more confident to approach patients; motivate them; increase their awareness of themselves and others; strengthen, deepen, and contextualise their theoretical knowledge; teach intellectual skills; strengthen learning of behavioural and social sciences; and teach them about the role of health professionals. <b>Conclusion</b> A rationale for early experience would be to strengthen and deepen cognitively, broaden affectively, contextualise, and integrate medical education. This is partly a process of professional socialisation that should start earlier to avoid an abrupt transition. "Experience" can be defined as "authentic human contact in a social or clinical context that enhances learning of health, illness or disease, and the role of the health professional."
Pharmacology of Brain Epinephrine Neurons
Authors: R W Fuller
Journal: The Annual Review of Pharmacology and Toxicology (1982)

Neurons that contain PNMT, the epinephrine-forming enzyme, have their cell bodies in brain stem regions in rat brain and send projections mainly into other brain stem areas, hypothalamus, and spinal cord. These neurons can be affected pharmacologically by various kinds of drugs. Epinephrine neuronal systems might play a part in some pharmacologic actions of MAO inhibitors and uptake inhibitors as well as alpha and beta agonists and antagonists. PNMT inhibitors currently represent the only means of modifying epinephrine neurons pharmacologically without also altering norepinephrine or dopamine neurons in brain. The continued study of drugs affecting epinephrine neurons should be useful in elucidating functions of these neurons. Drugs that affect epinephrine neurons may be of use in the treatment of hypertension, psychiatric disorders, neuroendocrine dysfunction, and possibly other diseases.
Serial Intravascular Ultrasound Assessment of the Efficacy of Intracoronary γ-Radiation Therapy for Preventing Recurrence in Very Long, Diffuse, In-Stent Restenosis Lesions
Authors: Javed M. Ahmed, Gary S. Mintz, Ron Waksman, Roxana Mehran, Borjanka Leiboff, Augusto D. Pichard, Lowell F. Satler, Kenneth M. Kent, Neil J. Weissman
Journal: Circulation (2001)

Background — The efficacy of coronary γ-irradiation in preventing recurrent in-stent restenosis (ISR) is well established. However, brachytherapy may be less effective in very long, diffuse ISR lesions. Methods and Results — We used serial intravascular ultrasound (IVUS) to study patients with long, diffuse ISR lesions (length, 36 to 80 mm) who were enrolled in (1) Long WRIST (Washington Radiation In-Stent Restenosis Trial), a double-blind, placebo-controlled trial of intracoronary γ-irradiation (15 Gy at 2 mm from the source) and (2) high-dose (HD) Long WRIST, a registry that used a dose prescription of 18 Gy at 2 mm from the source. IVUS was performed using automated pullback (0.5 mm/s). Stent, lumen, and intimal hyperplasia were measured at 2-mm intervals. Complete postintervention and follow-up IVUS imaging was available in 30 irradiated and 34 placebo patients from Long WRIST and in 25 patients from HD Long WRIST. Stent length was longer in HD Long WRIST than in placebo or treated patients in Long WRIST ( P =0.0064 and P =0.0125, respectively). Otherwise, baseline measurements were similar. At follow-up, the minimum lumen area was largest in the HD Long WRIST patients (4.0±1.4 mm 2 ); areas were 2.9±1.0 mm 2 in irradiated patients in Long WRIST and 1.9±1.1 mm 2 in placebo patients in Long WRIST ( P &lt;0.005 for all comparisons). Conclusions — Serial IVUS analysis shows that γ-irradiation reduces recurrent in-stent neointimal hyperplasia in long, diffuse ISR lesions; however, it is even more effective when given at a higher dose.
E2F2 expression induces proliferation of terminally differentiated cardiomyocytes in vivo
Authors: H. Ebelt, Y. Zhang, A. Kampke, J. Xu, A. Schlitt, M. Buerke, U. Muller-Werdan, K. Werdan, T. Braun
Journal: Cardiovascular Research (2008)

AimsIn previous experiments we have demonstrated that expression of the transcription factors E2F2 and E2F4 is sufficient to induce proliferation of isolated primary cardiomyocytes from newborn rats and mice. We now wanted to analyse whether E2F2 or E2F4 are also able to promote cell cycle progression of adult cardiomyocytes in vivo, which unlike cardiomyocytes from newborn rodents lack the ability to undergo cell proliferation.
Repeatability of cellular and soluble markers of inflammation in induced sputum from patients with asthma
Authors: JC in 't Veen, HW de Gouw, HH Smits, JK Sont, PS Hiemstra, PJ Sterk, EH Bel
Journal: European Respiratory Journal (1996)

Sputum induced by inhalation of nebulized hypertonic saline is increasingly used to monitor airways inflammation in asthma. The aim of this study was to assess the repeatability of measuring cellular and soluble markers of inflammation in whole sputum samples as obtained by sputum induction in patients both with mild and moderate-to-severe asthma. Twelve patients with mild, atopic asthma without inhaled steroid treatment and nine patients with moderate-to-severe, atopic asthma treated with inhaled steroids were studied on two separate days at least 2 days apart. Whole sputum samples, induced by inhalation of hypertonic (4.5%) saline, were homogenized, and analysed for differential cell counts and for concentrations of albumin, fibrinogen, interleukin-8 (IL-8), and eosinophil cationic protein (ECP). Repeatability was expressed as intraclass correlation coefficient (Ri), and as coefficient of repeatability (CR) in percentage cells or in doubling concentration. Samples from two patients with mild asthma contained more than 80% squamous cells and were excluded from analysis. The repeatability for cell differential counts in both groups combined was: for neutrophils, Ri = 0.57 and CR = 31.0; for eosinophils, Ri = 0.85 and CR = 12.4; and for lymphocytes, Ri = 0.76 and CR = 6.9. The repeatability of the fluid phase measurements was: for albumin, Ri = 0.71 and CR = 3.2; for fibrinogen, Ri = 0.88 and CR = 2.8; for IL-8, Ri = 0.66 and CR = 2.2; and for ECP, Ri = 0.82 and CR = 1.1. We conclude that the repeatability of cellular and soluble markers of inflammation in induced sputum from patients with mild and moderate-to-severe asthma is satisfactory. Hence, induced sputum, processed by using the whole expectorated sample, seems to be a valuable method to monitor airway inflammation in asthma.
Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study
Authors: K. Panoutsopoulou, L. Southam, K. S. Elliott, N. Wrayner, G. Zhai, C. Beazley, G. Thorleifsson, N. K. Arden, A. Carr, K. Chapman, P. Deloukas, M. Doherty, A. McCaskie, W. E. R. Ollier, S. H. Ralston, T. D. Spector, A. M. Valdes, G. A. Wallis, J. M. Wilkinson, E. Arden, K. Battley, H. Blackburn, F. J. Blanco, S. Bumpstead, L. A. Cupples, A. G. Day-Williams, K. Dixon, S. A. Doherty, T. Esko, E. Evangelou, D. Felson, J. J. Gomez-Reino, A. Gonzalez, A. Gordon, R. Gwilliam, B. V. Halldorsson, V. B. Hauksson, A. Hofman, S. E. Hunt, J. P. A. Ioannidis, T. Ingvarsson, I. Jonsdottir, H. Jonsson, R. Keen, H. J. M. Kerkhof, M. G. Kloppenburg, N. Koller, N. Lakenberg, N. E. Lane, A. T. Lee, A. Metspalu, I. Meulenbelt, M. C. Nevitt, F. O'Neill, N. Parimi, S. C. Potter, I. Rego-Perez, J. A. Riancho, K. Sherburn, P. E. Slagboom, K. Stefansson, U. Styrkarsdottir, M. Sumillera, D. Swift, U. Thorsteinsdottir, A. Tsezou, A. G. Uitterlinden, J. B. J. van Meurs, B. Watkins, M. Wheeler, S. Mitchell, Y. Zhu, J. M. Zmuda, E. Zeggini, J. Loughlin
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> The genetic aetiology of osteoarthritis has not yet been elucidated. To enable a well-powered genome-wide association study (GWAS) for osteoarthritis, the authors have formed the arcOGEN Consortium, a UK-wide collaborative effort aiming to scan genome-wide over 7500 osteoarthritis cases in a two-stage genome-wide association scan. Here the authors report the findings of the stage 1 interim analysis. <h3>Methods</h3> The authors have performed a genome-wide association scan for knee and hip osteoarthritis in 3177 cases and 4894 population-based controls from the UK. Replication of promising signals was carried out in silico in five further scans (44 449 individuals), and de novo in 14 534 independent samples, all of European descent. <h3>Results</h3> None of the association signals the authors identified reach genome-wide levels of statistical significance, therefore stressing the need for corroboration in sample sets of a larger size. Application of analytical approaches to examine the allelic architecture of disease to the stage 1 genome-wide association scan data suggests that osteoarthritis is a highly polygenic disease with multiple risk variants conferring small effects. <h3>Conclusions</h3> Identifying loci conferring susceptibility to osteoarthritis will require large-scale sample sizes and well-defined phenotypes to minimise heterogeneity.
Does isolated diastolic dysfunction exist in hypertensive patients with ecg determined left ventricular hypertrophy: the LIFE study
Authors: K. Wachell, V. Papademetriou, G. Smith, E. Gerdits, M. Nieminen, J.N. Bella, J. Rokkedal, R.B. Devereux
Journal: Journal of the American College of Cardiology (1998)
A Pathogenic Role for Myelin-Specific Cd8+ T Cells in a Model for Multiple Sclerosis
Authors: Eric S. Huseby, Denny Liggitt, Thea Brabb, Bryan Schnabel, Claes Öhlén, Joan Goverman
Journal: The Journal of Experimental Medicine (2001)

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) characterized by plaques of infiltrating CD4+ and CD8+ T cells. Studies of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, focus on the contribution of CD4+ myelin-specific T cells. The role of CD8+ myelin-specific T cells in mediating EAE or MS has not been described previously. Here, we demonstrate that myelin-specific CD8+ T cells induce severe CNS autoimmunity in mice. The pathology and clinical symptoms in CD8+ T cell–mediated CNS autoimmunity demonstrate similarities to MS not seen in myelin-specific CD4+ T cell–mediated EAE. These data suggest that myelin-specific CD8+ T cells could function as effector cells in the pathogenesis of MS.