tbuckley/cabot-search huggingface dataset:
The Production of a New MAGE-3 Peptide Presented to Cytolytic T Lymphocytes by HLA-B40 Requires the Immunoproteasome
Authors: Erwin S. Schultz, Jacques Chapiro, Christophe Lurquin, Stéphane Claverol, Odile Burlet-Schiltz, Guy Warnier, Vincenzo Russo, Sandra Morel, Frédéric Lévy, Thierry Boon, Benoît J. Van den Eynde, Pierre van der Bruggen
Journal: The Journal of Experimental Medicine (2002)

By stimulating human CD8+ T lymphocytes with autologous dendritic cells infected with an adenovirus encoding MAGE-3, we obtained a cytotoxic T lymphocyte (CTL) clone that recognized a new MAGE-3 antigenic peptide, AELVHFLLL, which is presented by HLA-B40. This peptide is also encoded by MAGE-12. The CTL clone recognized MAGE-3–expressing tumor cells only when they were first treated with IFN-γ. Since this treatment is known to induce the exchange of the three catalytic subunits of the proteasome to form the immunoproteasome, this result suggested that the processing of this MAGE-3 peptide required the immunoproteasome. Transfection experiments showed that the substitution of β5i (LMP7) for β5 is necessary and sufficient for producing the peptide, whereas a mutated form of β5i (LMP7) lacking the catalytically active site was ineffective. Mass spectrometric analyses of in vitro digestions of a long precursor peptide with either proteasome type showed that the immunoproteasome produced the antigenic peptide more efficiently, whereas the standard proteasome more efficiently introduced cleavages destroying the antigenic peptide. This is the first example of a tumor-specific antigen exclusively presented by tumor cells expressing the immunoproteasome.
Multiple-dose activated charcoal for treatment of yellow oleander poisoning: a single-blind, randomised, placebo-controlled trial
Authors: HA de Silva, MMD Fonseka, A Pathmeswaran, DGS Alahakone, GA Ratnatilake, SB Gunatilake, CD Ranasinha, DG Lalloo, JK Aronson, HJ de Silva
Journal: The Lancet (2003)
Plasma Testosterone and Prognosis of Postmenopausal Breast Cancer Patients
Authors: Andrea Micheli, Elisabetta Meneghini, Giorgio Secreto, Franco Berrino, Elisabetta Venturelli, Adalberto Cavalleri, Tiziana Camerini, Maria G. Di Mauro, Elena Cavadini, Giuseppe De Palo, Umberto Veronesi, Franca Formelli
Journal: Journal of Clinical Oncology (2007)

Purpose High endogenous testosterone is associated with increased breast cancer (BC) risk. We designed this study specifically to assess the long-term prognostic role of testosterone in a cohort of postmenopausal BC patients. Patients and Methods We considered 194 postmenopausal women, operated on for early BC (T1-2N0M0), who never received chemotherapy or hormonal therapy, and who participated in a fenretinide BC prevention trial as untreated controls. Blood samples were collected 3 months (median) after surgery; plasma samples, stored at −80°C, were radioimmunoassayed for testosterone. Median follow-up was 14 years. The main end point was any cancer event. Event-free survival was estimated by the Kaplan-Meier method. Hazard ratios (HRs) of events by testosterone level were estimated by the Cox model, adjusting for age, tumor size, and histology. Results Patients with high testosterone (≥ 0.40 ng/mL, median of distribution) had significantly lower event-free survival than those with low testosterone (log-rank P = .004). The adjusted HR of patients with high versus low testosterone was 2.05 (95% CI, 1.28 to 3.27). High testosterone was also associated with a significantly higher risk of BC events (relapse and second primary) with an adjusted HR of 1.77 (95% CI, 1.06 to 2.96). Eleven second primaries (non-BC) occurred in the high-testosterone group, four in the low-testosterone group. Conclusion High plasma testosterone strongly predicts poorer prognosis in postmenopausal BC patients not administered adjuvant therapy. Testosterone levels should be determined as part of the prognostic work-up.
Sex, aggression, and life history strategy
Authors: Aurelio José Figueredo, Paul Robert Gladden, Barbara Hagenah Brumbach
Journal: Behavioral and Brain Sciences (2009)

Abstract We agree that sexual selection is a more comprehensive explanation for sex differences in direct aggression than social role theory, which is an unparsimonious and vestigial remnant of human exceptionalism. Nevertheless, Archer misses several opportunities to put the theoretical predictions made by himself and by others into direct competition in a way that would further the interests of strong inference.
Smoking and delay to diagnosis are associated with poorer functional outcome in psoriatic arthritis
Authors: William Tillett, Deepak Jadon, Gavin Shaddick, Charlotte Cavill, Eleanor Korendowych, Corinne S de Vries, Neil McHugh
Journal: Annals of the Rheumatic Diseases (2013)

To identify predictors of poorer physical function in established psoriatic arthritis (PsA).PsA patients with disease duration of ≥10 years were identified from the Bath longitudinal cohort. Physical function was assessed using the Stanford Health Assessment Questionnaire (HAQ). Sex, age at diagnosis, duration of symptoms prior to diagnosis, smoking, treatment and year of diagnosis were included in a multivariable regression analysis to identify associations with HAQ.267 patients were identified for inclusion. The median age was 56 years (IQR 45-63), median disease duration was 13 years (IQR 10-18) and median HAQ score was 0.63 (IQR 0.13-1.25). The model predicted significant increases in HAQ related to smoking (0.23, 95% CI 0.04 to 0.42), age >50 years at diagnosis (0.27, 95% CI 0.03 to 0.51), symptom duration of ≥1 year before diagnosis (0.22, 95% CI 0.02 to 0.42), female sex (0.39, 95% CI 0.20 to 0.57) and history of treatment with an anti-TNF agent (0.63, 95% CI 0.32 to 0.93) at follow-up.Smoking, delay to diagnosis, older age at diagnosis, female sex and a history of anti-TNF treatment are associated with worse physical function in established PsA.
Anti-Inflammatory Mechanisms in the Vascular Wall
Authors: Alain Tedgui, Ziad Mallat
Journal: Circulation Research (2001)

Abstract —The role of vascular cells during inflammation is critical and is of particular importance in inflammatory diseases, including atherosclerosis, ischemia/reperfusion, and septic shock. Research in vascular biology has progressed remarkably in the last decade, resulting in a better understanding of the vascular cell responses to inflammatory stimuli. Most of the vascular inflammatory responses are mediated through the IκB/nuclear factor-κB system. Much recent work shows that vascular inflammation can be limited by anti-inflammatory counteregulatory mechanisms that maintain the integrity and homeostasis of the vascular wall. The anti-inflammatory mechanisms in the vascular wall involve anti-inflammatory external signals and intracellular mediators. The anti-inflammatory external signals include the anti-inflammatory cytokines, transforming growth factor-β, interleukin-10 and interleukin-1 receptor antagonist, HDL, as well as some angiogenic and growth factors. Physiological laminar shear stress is of particular importance in protecting endothelial cells against inflammatory activation. Its effects are partly mediated through NO production. Finally, endogenous cytoprotective genes or nuclear receptors, such as the peroxisome proliferator–activated receptors, can be expressed by vascular cells in response to proinflammatory stimuli to limit the inflammatory process and the injury.
A pilot study on changes of macrophage colony stimulating factor and transforming growth factor 1 in male patients with ankylosing spondylitis taking thalidomide
Authors: P. Yang, W. Xiao, L. Qin, L. Zhao, L. He, M. Ito
Journal: Annals of the Rheumatic Diseases (2009)

Ankylosing spondylitis (AS) is a progressive disease of which spinal fusion is the clinical and pathological hallmark. Thalidomide has some efficacy in treating axial inflammation in AS.1 Here, we report clinical responses and changes of serum macrophage colony stimulating factor (M-CSF) and transforming growth factor β1 (TGFβ1) in Chinese male patients with active AS taking thalidomide.

This study enrolled 29 male patients with active AS, whose Bath ankylosing spondylitis disease activity index (BASDAI) was 3 or above.2 A total of 16 patients not intending to have children within the next 2 years took thalidomide (75 mg every night postoperatively) and diclofenac sodium (50 mg 3 times a day postoperatively) for 12 weeks; other patients took diclofenac sodium (50 mg 3 times a day postoperatively) alone. There were no …
Measuring the Sensitivity of Single-locus "Neutrality Tests" Using a Direct Perturbation Approach
Authors: D. Garrigan, R. Lewontin, J. Wakeley
Journal: Molecular Biology and Evolution (2009)

A large number of statistical tests have been proposed to detect natural selection based on a sample of variation at a single genetic locus. These tests measure the deviation of the allelic frequency distribution observed within populations from the distribution expected under a set of assumptions that includes both neutral evolution and equilibrium population demography. The present study considers a new way to assess the statistical properties of these tests of selection, by their behavior in response to direct perturbations of the steady-state allelic frequency distribution, unconstrained by any particular nonequilibrium demographic scenario. Results from Monte Carlo computer simulations indicate that most tests of selection are more sensitive to perturbations of the allele frequency distribution that increase the variance in allele frequencies than to perturbations that decrease the variance. Simulations also demonstrate that it requires, on average, 4N generations (N is the diploid effective population size) for tests of selection to relax to their theoretical, steady-state distributions following different perturbations of the allele frequency distribution to its extremes. This relatively long relaxation time highlights the fact that these tests are not robust to violations of the other assumptions of the null model besides neutrality. Lastly, genetic variation arising under an example of a regularly cycling demographic scenario is simulated. Tests of selection performed on this last set of simulated data confirm the confounding nature of these tests for the inference of natural selection, under a demographic scenario that likely holds for many species. The utility of using empirical, genomic distributions of test statistics, instead of the theoretical steady-state distribution, is discussed as an alternative for improving the statistical inference of natural selection.
Aortic Aneurysm and Dissection in Giant Cell Arteritis
Authors: Robert Ginsburg
Journal: Annals of Internal Medicine (1996)

Letters15 March 1996Aortic Aneurysm and Dissection in Giant Cell ArteritisRobert Ginsburg, MDRobert Ginsburg, MDUniversity of Colorado Health Sciences Center; Denver, CO 80262Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-6-199603150-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The population review by Evans and colleagues [1] suggested an association between giant cell arteritis and aortic (thoracic and abdominal) aneurysms. The authors recommended that patients have an annual examination that includes palpation of the abdomen and a chest radiograph. Because polymyalgia rheumatica (with or without biopsy-proven giant cell arteritis) occurs in a population with many comorbid conditions, the true incidence of aortic disease has been difficult to assess. Regardless of statistical verification, however, a physical examination of the abdomen by any physician, especially rheumatologists who may see many associated vascular diseases, should always include palpation of ...References1. Evans JM, O'Fallon WM, Hunder GG. Increased incidence of aortic aneurysm and dissection in giant cell (temporal) arteritis. A populationbased study. Ann Intern Med. 1995; 122:502-7. Google Scholar2. Dake MD, Miller DC, Semba CP, Mitchell RS, Walker PJ, Liddell RP. Transluminal placement of endovascular stent-grafts for the treatment of descending thoracic aortic aneurysms. N Engl J Med. 1994; 331:1729-33. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Colorado Health Sciences Center; Denver, CO 80262 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByEndovascular Therapy for Aortic Dissection 15 March 1996Volume 124, Issue 6Page: 615KeywordsAneurysmsAortaGiant cellsMorbidityPolymyalgia rheumaticaShouldersStiffnessSurgeryThoraxVascular diseases Issue Published: 15 March 1996 CopyrightCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Entopic overexpression of<i>Ascl2</i>does not accelerate tumourigenesis in Apc<sup>Min</sup>mice
Authors: Karen R Reed, Simon J Tunster, Madeleine Young, Adam Carrico, Rosalind M John, Alan R Clarke
Journal: Gut (2011)

<h3>Objective</h3> Expression of the Wnt target gene <i>ASCL2</i> is elevated in 78% of intestinal neoplasia datasets (Oncomine), suggesting a role for deregulated <i>ASCL2</i> in the aetiology of intestinal tumourigenesis. Furthermore, ectopic expression of <i>Ascl2</i> has previously been shown to lead to hyperplasia in the mouse. However, elevated levels of <i>ASCL2</i> does not have an impact on the overall survival or recurrence-free survival rates in colorectal cancer patients. Here the authors use a novel mouse model to analyse the role of <i>Ascl2</i> in intestinal tumourigenesis and address the controversy surrounding the relevance of this gene to the aetiology of colorectal cancer. <h3>Design</h3> The authors have generated a mouse possessing a transgene carrying the <i>Ascl2</i> gene together with its endogenous promoter and regulatory regions, thereby elevating <i>Ascl2</i> expression in an authentic manner. The authors have further intercrossed these <i>Ascl2</i> overexpressers to the classic <i>Apc<sup>Min</sup></i> model, to study the consequence of elevated <i>Ascl2</i> expression in intestinal tumourigenesis. <h3>Results</h3> Here the authors genetically demonstrate that elevated expression of <i>Ascl2</i> in a Wnt signalling dependent manner specifically in the stem cell compartment of the intestine neither increases tumour formation nor diminishes survival in a well established intestinal tumour model, the <i>Apc<sup>min</sup></i> mouse. <h3>Conclusion</h3> The authors conclude that ectopic expression of <i>Ascl2</i> is more important in the aetiology of neoplasia than overexpression of <i>Ascl2</i>.
Effect of body position on measurements of diffusion capacity after exercise
Authors: Ian B Stewart, Jim E Potts, Don C McKenzie, Ken D Coutts
Journal: British Journal of Sports Medicine (2000)

Pulmonary diffusing capacity for carbon monoxide (D1co), alveolar capillary membrane diffusing capacity (Dm), and pulmonary capillary blood volume (Vc) are all significantly reduced after exercise.To investigate whether measurement position affects this impaired gas transfer.Before and one, two, and four hours after incremental cycle ergometer exercise to fatigue, single breath D1co, Dm, and Vc measurements were obtained in 10 healthy men in a randomly assigned supine and upright seated position.After exercise, D1co, Dm, and Vc were significantly depressed compared with baseline in both positions. The supine position produced significantly higher values over time for D1co (5.22 (0.13) v. 4.66 (0.15) ml/min/mm Hg/l, p = 0.022) and Dm (6.78 (0.19) v. 6.03 (0.19) ml/min/mm Hg/l, p = 0.016), but there was no significant position effect for Vc. There was a similar pattern of change over time for D1co, Dm, and Vc in the two positions.The change in D1co after exercise appears to be primarily due to a decrease in Vc. Although the mechanism for the reduction in Vc cannot be determined from these data, passive relocation of blood to the periphery as the result of gravity can be discounted, suggesting that active vasoconstriction of the pulmonary vasculature and/or peripheral vasodilatation is occurring after exercise.
Effects of a Protein Preload on Gastric Emptying, Glycemia, and Gut Hormones After a Carbohydrate Meal in Diet-Controlled Type 2 Diabetes
Authors: Jing Ma, Julie E. Stevens, Kimberly Cukier, Anne F. Maddox, Judith M. Wishart, Karen L. Jones, Peter M. Clifton, Michael Horowitz, Christopher K. Rayner
Journal: Diabetes Care (2009)

OBJECTIVE We evaluated whether a whey preload could slow gastric emptying, stimulate incretin hormones, and attenuate postprandial glycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS Eight type 2 diabetic patients ingested 350 ml beef soup 30 min before a potato meal; 55 g whey was added to either the soup (whey preload) or potato (whey in meal) or no whey was given. RESULTS Gastric emptying was slowest after the whey preload (P &amp;lt; 0.0005). The incremental area under the blood glucose curve was less after the whey preload and whey in meal than after no whey (P &amp;lt; 0.005). Plasma glucose-dependent insulinotropic polypeptide, insulin, and cholecystokinin concentrations were higher on both whey days than after no whey, whereas glucagon-like peptide 1 was greatest after the whey preload (P &amp;lt; 0.05). CONCLUSIONS Whey protein consumed before a carbohydrate meal can stimulate insulin and incretin hormone secretion and slow gastric emptying, leading to marked reduction in postprandial glycemia in type 2 diabetes.
Two subsets of human T lymphocytes expressing gamma/delta antigen receptor are identifiable by monoclonal antibodies directed to two distinct molecular forms of the receptor.
Authors: C Bottino, G Tambussi, S Ferrini, E Ciccone, P Varese, M C Mingari, L Moretta, A Moretta
Journal: The Journal of Experimental Medicine (1988)

Two mAbs directed to the TCR-gamma/delta were analyzed for their pattern of reactivity with CD3+WT31- cell populations or clones. In normal individuals, the BB3 mAb reacted with approximately 2/3 of peripheral blood CD3+WT31- lymphocytes, whereas delta-TCS-1 stained approximately 1/3 of such cells. In addition, the sum of the percentages of BB3+ and delta-TCS-1+ cells approximated the percentages of peripheral blood CD3+WT31- lymphocytes in seven normal donors tested. Also, in peripheral blood-derived polyclonal CD3+WT31- populations, cultured in IL-2, cells reacting with one or another mAb accounted for the whole cell population. On the other hand, only delta-TCS-1-reactive cells, but not BB3+ cells, could be detected in unfractionated as well as in CD4-8-thymocyte populations. Analysis of peripheral blood-derived CD3+WT31- clones showed that 70% of 72 clones analyzed reacted with BB3 mAb, but not with delta-TCS-1 mAb. On the other hand, delta-TCS-1 mAb stained the remaining BB3- clones. Five clones expressing medium-low amounts of CD8 antigen were BB3- delta-TCS-1+. Both types of clones lysed the Fc gamma receptor-bearing P815 target cell in the presence of anti-CD3 mAb (but not of mAb directed against HLA-DR, CD7 molecules, or TCR-alpha/beta). In this cytolytic assay, BB3 mAb induced target cell lysis only by BB3+ clones, whereas delta-TCS-1 mAb was effective only with delta-TCS-1+ clones. The CD3-associated surface molecules expressed by BB3+ or delta-TCS-1+ clones were analyzed after cell surface iodination and immunoprecipitation with the corresponding anti-TCR mAb or with anti-CD3 mAb (in digitonin-containing buffer). In SDS-PAGE, molecules immunoprecipitated from 13 BB3+ clones displayed, under nonreducing conditions, a molecular weight of 80 kD (in some cases, a minor 38-kD band could be detected). Under reducing conditions, two major components of 44 and 41 kD (and a minor component of 38 kD) were detected. On the other hand, TCR molecules immunoprecipitated from 11 different delta-TCS-1+ clones appeared as a diffuse band of 41-44 kD, both under reducing and nonreducing conditions (under non-reducing condition, an additional 38-kD band was present). Therefore, BB3+ cells express a disulphide-linked form of TCR-gamma/delta whereas delta-TCS-1+ cells express a non-disulphide-linked form.(ABSTRACT TRUNCATED AT 400 WORDS)
Detection of IgG and IgA against the mycobacterial antigen A60 in patients with extrapulmonary tuberculosis
Authors: M. Alifano, R. De Pascalis, M. Sofia, S. Faraone, M. Del Pezzo, I. Covelli
Journal: Thorax (1998)

<h3>BACKGROUND</h3> Diagnosis of extrapulmonary tuberculosis is often difficult to establish using standard methods. Serological techniques based on detection of antibodies against mycobacterial antigen A60 have shown good sensitivity and specificity in pulmonary tuberculosis. The present study was undertaken to define the diagnostic accuracy of testing for IgG and IgA against A60 in extrapulmonary tuberculosis. <h3>METHODS</h3> One hundred and ninety eight subjects were studied: 42 patients with extrapulmonary tuberculosis confirmed by microbiology and/or histology, 24 subjects with healed pulmonary or extrapulmonary tuberculosis, 44 patients with a defined non-tuberculous disease, and 88 healthy volunteers (44 PPD negative and 44 PPD positive). Detection of IgG and IgA against A60 antigen was carried out by enzyme-linked immunosorbent assay. Cut off values were determined by receiver operating characteristic curves. <h3>RESULTS</h3> Sensitivity of the IgG test was 73.8% in extrapulmonary tuberculosis, while the specificity was 96.1%. The IgA test showed a sensitivity of 69.0% with a specificity of 93.6%. Combination of the IgG and IgA tests showed a sensitivity of 80.9% and a specificity of 92.3%. Patients with extrapulmonary tuberculosis showed significantly higher titres of both IgG and IgA against A60 than other groups. <h3>CONCLUSIONS</h3> Anti-A60 IgG or IgA tests are characterised by good sensitivity and specificity. The combined use of both tests allows an increase in diagnostic accuracy of extrapulmonary tuberculosis.
Rational Approach to AIDS Drug Design Through Structural Biology
Authors: Alexander Wlodawer
Journal: Annual Review of Medicine (2002)

The discovery and development of more than a dozen drugs in the past 15 years for the treatment of AIDS offer an excellent example of progress in the field of rational drug design. At this time, the principal targets are reverse transcriptase and protease, enzymes encoded by the human immunodeficiency virus. The introduction of protease inhibitors, in particular, has drastically decreased the mortality and morbidity associated with AIDS. This review presents the methods used to develop such drugs and discusses the remaining problems, such as the rapid emergence of drug resistance.
Pertuzumab Pharmacokinetics and Safety in Combination with Trastuzumab and Chemotherapy in Patients with Her2-Positive Advanced Gastric Cancer (Agc)
Authors: Yoon-Koo Kang, Sun Young Rha, Pierfrancesco Tassone, Jorge Barriuso, Ron Yu, Tania Szado, Amit Garg, Yung-Jue Bang
Journal: Annals of Oncology (2013)