tbuckley/cabot-search huggingface dataset:
Reversal of Spontaneous Autoimmune Insulitis in Nonobese Diabetic Mice by Soluble Lymphotoxin Receptor
Authors: Qiang Wu, Benoît Salomon, Min Chen, Yang Wang, Lisa M. Hoffman, Jeffrey A. Bluestone, Yang-Xin Fu
Journal: The Journal of Experimental Medicine (2001)

One striking feature of spontaneous autoimmune diabetes is the prototypic formation of lymphoid follicular structures within the pancreas. Lymphotoxin (LT) has been shown to play an important role in the formation of lymphoid follicles in the spleen. To explore the potential role of LT-mediated microenvironment in the pathogenesis of insulin-dependent diabetes mellitus (IDDM), an LTbeta receptor-immunoglobulin fusion protein (LTbetaR-Ig) was administered to nonobese diabetic mice. Early treatment with LTbetaR-Ig prevented insulitis and IDDM, suggesting that LT plays a critical role in the insulitis development. LTbetaR-Ig treatment at a late stage of the disease also dramatically reversed insulitis and prevented diabetes. Moreover, LTbetaR-Ig treatment prevented the development of IDDM by diabetogenic T cells in an adoptive transfer model. Thus, LTbetaR-Ig can disassemble the well established lymphoid microenvironment in the islets, which is required for the development and progression of IDDM.
Altered matrix production in the distal airways of individuals with asthma
Authors: K. Nihlberg, A. Andersson-Sjoland, E. Tufvesson, J. S. Erjefalt, L. Bjermer, G. Westergren-Thorsson
Journal: Thorax (2010)

<h3>Background and aims</h3> Although increasing evidence suggests involvement of the distal airway in all stages of asthma, it is not known whether structural changes (defined as airway remodelling) occur in the distal airways of subjects with mild asthma and those with atopy. The aim of this study was to compare control subjects and those with mild asthma in relation to fibroblast phenotypes and remodelling in central and distal airways. <h3>Methods</h3> Distal and central fibroblasts from controls (n=12) and patients with mild asthma (n=11) were cultured and incubated for 24 h with 0.4% serum, or stimulated with transforming growth factor β1 (TGFβ1). [<sup>35</sup>S]Sulfate-labelled proteoglycans in culture medium were analysed by ion exchange chromatography and sodium dodecyl sulfate–polyacrylamide gel electrophoresis. Proliferation was measured with crystal violet, and exhaled nitric oxide was measured by the fractional nitric oxide technique. <h3>Results</h3> Vesican production from distal fibroblasts was significantly elevated in patients with asthma compared with controls (p&lt;0.001), and the percentage collagen-positive area in distal asthma tissue was also enhanced compared with controls (p&lt;0.01). In addition, distal asthma fibroblasts had reduced proliferation capacity compared with those of controls (by 24%; p&lt;0.01). Furthermore, the alveolar nitric oxide concentration was correlated to distal biglycan and perlecan production of subjects with asthma (r=−0.857, p&lt;0.05 and r=−0.750, p&lt;0.05 respectively) <h3>Conclusion</h3> It is shown that centrally and distally derived fibroblasts differ in their proteoglycan production and proliferation between central and distal tissue, and in those with asthma compared with controls. It is also demonstrated that remodelling is present in distal lung of subjects with mild asthma. This may be of importance in airway remodelling and asthma progression.
Tolerance Induction in an Interim Analysis of Peanut Sublingual Immunotherapy
Authors: Edwin Kim, Stacy Chin, Pamela H. Steele, Janet S. Kamilaris, Nikolas Kamilaris, Caitlin Burk, Brian P. Vickery, Michael D. Kulis, A. Wesley Burks
Journal: Journal of Allergy and Clinical Immunology (2013)
Models for Intensive Care Training. A European Perspective
Authors: Julian Bion, Hans U. Rothen
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Section:ChooseTop of pageAbstract <<Worldwide Survey of Train...Specialty Status and Euro...Competency-based Training...Impact and Further Develo...Specialty Status of ICMQuality Assurance and Rec...Strengths of the CoBaTrIC...Challenges and Opportunit...Professionalism: Scholars...Professionalism: Reflecti...Assessment of Professiona...Outcomes: A Research Fram...ReferencesCITING ARTICLES
Mediation of a non-proteolytic activation of complement component C3 by phospholipid vesicles
Authors: Yvonne Klapper, Osama A. Hamad, Yuji Teramura, Gero Leneweit, G. Ulrich Nienhaus, Daniel Ricklin, John D. Lambris, Kristina N. Ekdahl, Bo Nilsson
Journal: Biomaterials (2014)
ANTIGEN SAMPLING ACROSS EPITHELIAL BARRIERS AND INDUCTION OF MUCOSAL IMMUNE RESPONSES
Authors: Marian R. Neutra, Eric Pringault, Jean-Pierre Kraehenbuhl
Journal: Annual Review of Immunology (1996)

Epithelial barriers on mucosal surfaces at different sites in the body differ dramatically in their cellular organization, and antigen sampling strategies at diverse mucosal sites are adapted accordingly. In stratified and pseudostratified epithelia, dendritic cells migrate to the outer limit of the epithelium, where they sample antigens for subsequent presentation in local or distant organized lymphoid tissues. In simple epithelia, specialized epithelial M cells (a phenotype that occurs only in the epithelium over organized lymphoid follicles) deliver samples of foreign material by transepithelial transport from the lumen to organized lymphoid tissues within the mucosa. Certain pathogens exploit the M cell transport process to cross the epithelial barrier and invade the mucosa. Here we review the features of M cells that determine antigen and pathogen adherence and transport into mucosal lymphoid tissues.
Viral entry inhibition: too late for hepatitis C, but promising for other viral infections
Authors: Jean-Michel Pawlotsky
Journal: Gut (2014)

In theory, any step of the hepatitis C virus (HCV) lifecycle can be a target for direct-acting antiviral (DAA) drugs (drugs that directly block a viral function), and/or host-targeted agents (HTA, drugs that block a cellular function essential to the viral lifecycle). Four classes of HCV DAAs and two classes of HTAs have reached late clinical development. The HCV DAAs include: inhibitors of the NS3/4A protease that block HCV polyprotein processing; inhibitors of the RNA-dependent RNA polymerase (RdRp), including nucleoside/nucleotide analogues and non-nucleoside inhibitors that block viral replication; and NS5A inhibitors that block viral replication, virion assembly and release. The HCV HTAs in development interact with cellular factors required for HCV replication; they include cyclophilin A inhibitors and microRNA-122 antagonists.1

In 2014, three drugs were approved in the European Union, including the nucleotide analogue sofosbuvir, the protease inhibitor simeprevir and the NS5A inhibitor daclatasvir. They can be used in combination with pegylated interferon α (IFNα) and ribavirin, or as part of sofosbuvir-based IFN-free combinations.1 Other compounds will likely be approved before the end of 2014, including the NS5A inhibitor ledipasvir in combination with sofosbuvir in a single tablet, and the triple combination of the ritonavir-boosted protease inhibitor ABT-450 and the NS5A inhibitor ombitasvir in one tablet plus the non-nucleoside RdRp inhibitor dasabuvir. A number of other drugs from the same classes currently are in Phase II or III clinical development.

In vitro studies showed that other steps of the HCV lifecycle, such as entry, fusion, polyprotein translation, assembly, virion maturation or viral particle release can be blocked by means of specific or non-specific antiviral approaches. Viral entry appears as an attractive target, as suggested by the experience in other chronic viral infections. Two HIV entry inhibitors, maraviroc and enfuvirtide, have been approved and numerous other compounds have reached …
Central Command Increases Muscle Sympathetic Nerve Activity During Intense Intermittent Isometric Exercise in Humans
Authors: Ronald G. Victor, Niels H. Secher, Teresa Lyson, Jere H. Mitchell
Journal: Circulation Research (1995)

During sustained isometric exercise, central command has very little effect on muscle sympathetic nerve activity (MSNA). To determine if central command has a greater effect on MSNA during intermittent than during sustained contractions, MSNA was recorded with microelectrodes (peroneal nerve) during intermittent isometric handgrip at 25%, 50%, and 75% maximum voluntary contraction (MVC) in 9 human subjects with paced breathing. Similar experiments were performed in 11 additional subjects before and after partial neuromuscular blockade (intravenous curare) to isolate the influence of central command while minimizing force output and thus muscle afferent feedback. Before curare, handgrip at 25% and 50% MVC had no effect on MSNA, whereas handgrip at 75% MVC synchronized the MSNA to the handgrip such that MSNA was 5.7 +/- 1.3 times higher (mean +/- SEM, P < .001) during the contraction periods than during the relaxation periods. After curare, this synchronization of MSNA persisted without attenuation, even though force output fell to < 25% of the initial MVC. From these observations, we conclude that central command causes synchronization of motor activity and muscle sympathetic activity during intense intermittent isometric exercise.
The Impact of <i>EGFR</i> T790M Mutations and <i>BIM</i> mRNA Expression on Outcome in Patients with <i>EGFR</i>-Mutant NSCLC Treated with Erlotinib or Chemotherapy in the Randomized Phase III EURTAC Trial
Authors: Carlota Costa, Miguel Angel Molina, Ana Drozdowskyj, Ana Giménez-Capitán, Jordi Bertran-Alamillo, Niki Karachaliou, Radj Gervais, Bartomeu Massuti, Jia Wei, Teresa Moran, Margarita Majem, Enriqueta Felip, Enric Carcereny, Rosario Garcia-Campelo, Santiago Viteri, Miquel Taron, Mayumi Ono, Petros Giannikopoulos, Trever Bivona, Rafael Rosell
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Concomitant genetic alterations could account for transient clinical responses to tyrosine kinase inhibitors of the EGF receptor (EGFR) in patients harboring activating EGFR mutations. Experimental Design: We have evaluated the impact of pretreatment somatic EGFR T790M mutations, TP53 mutations, and Bcl-2 interacting mediator of cell death (BCL2L11, also known as BIM) mRNA expression in 95 patients with EGFR-mutant non–small-cell lung cancer (NSCLC) included in the EURTAC trial (trial registration: NCT00446225). Results: T790M mutations were detected in 65.26% of patients using our highly sensitive method based on laser microdissection and peptide-nucleic acid-clamping PCR, which can detect the mutation at an allelic dilution of 1 in 5,000. Progression-free survival (PFS) to erlotinib was 9.7 months for those with T790M mutations and 15.8 months for those without, whereas among patients receiving chemotherapy, it was 6 and 5.1 months, respectively (P &amp;lt; 0.0001). PFS to erlotinib was 12.9 months for those with high and 7.2 months for those with low/intermediate BCL2L11 expression levels, whereas among chemotherapy-treated patients, it was 5.8 and 5.5 months, respectively (P = 0.0003). Overall survival was 28.6 months for patients with high BCL2L11 expression and 22.1 months for those with low/intermediate BCL2L11 expression (P = 0.0364). Multivariate analyses showed that erlotinib was a marker of longer PFS (HR = 0.35; P = 0.0003), whereas high BCL2L11 expression was a marker of longer PFS (HR = 0.49; P = 0.0122) and overall survival (HR = 0.53; P = 0.0323). Conclusions: Low-level pretreatment T790M mutations can frequently be detected and can be used for customizing treatment with T790M-specific inhibitors. BCL2L11 mRNA expression is a biomarker of survival in EGFR-mutant NSCLC and can potentially be used for synthetic lethality therapies. Clin Cancer Res; 20(7); 2001–10. ©2014 AACR.
Erythropoietin Improves the Accumulation and Therapeutic Effects of Carboplatin by Enhancing Tumor Vascularization and Perfusion
Authors: Dennis Doleschel, Anne Rix, Susanne Arns, Karin Palmowski, Felix Gremse, Ruth Merkle, Florian Salopiata, Ursula Klingmüller, Michael Jarsch, Fabian Kiessling, Wiltrud Lederle
Journal: Theranostics (2015)

Recombinant human erythropoietin (rhuEpo) is currently under debate for the treatment of chemotherapy-induced anemia due to clinical trials showing adverse effects in Epo-treated patients and the discovery of the erythropoietin-receptor (EpoR) in tumor and endothelial cells.Here, using Epo-Cy5.5 as theranostic near-infrared fluorescent probe we analyzed the effects of rhuEpo as co-medication to carboplatin in non-small-cell-lung-cancer (NSCLC)-xenografts with different tumor cell EpoR-expression (H838 ~8-fold higher than A549).Nude mice bearing subcutaneous A549 and H838 NSCLC-xenografts received either only carboplatin or carboplatin and co-medication of rhuEpo in two different doses.Tumor sizes and relative blood volumes (rBV) were longitudinally measured by 3D-contrast-enhanced ultrasound (3D-US).Tumoral EpoR-levels were determined by combined fluorescence molecular tomography (FMT)/ micro computed tomography (µCT) hybrid imaging.We found that rhuEpo predominantly acted on the tumor endothelium.In both xenografts, rhuEpo co-medication significantly increased vessel densities, diameters and the amount of perfused vessels.Accordingly, rhuEpo induced EpoR-phoshorylation and stimulated proliferation of endothelial cells.However, compared with solely carboplatin-treated tumors, tumor growth was significantly slower in the groups co-medicated with rhuEpo.This is explained by the Epo-mediated vascular remodeling leading to improved drug delivery as obvious by a more than 2-fold higher carboplatin accumulation and significantly enhanced tumor apoptosis.In addition, co-medication of rhuEpo reduced tumor hypoxia and diminished intratumoral EpoR-levels which continuously increased during carboplatin (Cp) -treatment.These findings suggest that co-medication of rhuEpo in well balanced doses can be used to improve the accumulation of anticancer drugs.Doses and indications may be personalized and refined using theranostic EpoR-probes.
Intake of Fish and n3 Fatty Acids and Risk of Coronary Heart Disease Among Japanese
Authors: Hiroyasu Iso, Minatsu Kobayashi, Junko Ishihara, Satoshi Sasaki, Katsutoshi Okada, Yoshikuni Kita, Yoshihiro Kokubo, Shoichiro Tsugane
Journal: Circulation (2006)

Background— Once- or twice-weekly consumption of fish (or a small amount of fish intake) reduces the risk of coronary heart disease and sudden cardiac death in Western countries. It is uncertain whether a high frequency or large amount of fish intake, as is the case in Japan, further reduces the risk. Methods and Results— To examine an association between high intake of fish and n3 polyunsaturated fatty acids and the risk of coronary heart disease, a total of 41 578 Japanese men and women aged 40 to 59 years who were free of prior diagnosis of cardiovascular disease and cancer and who completed a food frequency questionnaire were followed up from 1990–1992 to 2001. After 477 325 person-years of follow-up, 258 incident cases of coronary heart disease (198 definite and 23 probable myocardial infarctions and 37 sudden cardiac deaths) were documented, comprising 196 nonfatal and 62 fatal coronary events. The multivariable hazard ratios (HRs) and 95% confidence intervals in the highest (8 times per week, or median intake=180 g/d) versus lowest (once a week, or median intake=23 g/d) quintiles of fish intake were 0.63 (0.38 to 1.04) for total coronary heart disease, 0.44 (0.24 to 0.81) for definite myocardial infarction, and 1.14 (0.36 to 3.63) for sudden cardiac death. The reduced risk was primarily observed for nonfatal coronary events (HR=0.43 [0.23 to 0.81]) but not for fatal coronary events (HR=1.08 [0.42 to 2.76]). Strong inverse associations existed between dietary intake of n3 fatty acids and risk of definite myocardial infarction (HR=0.35 [0.18 to 0.66]) and nonfatal coronary events (HR=0.33 [0.17 to 0.63]). Conclusions— Compared with a modest fish intake of once a week or &amp;20 g/d, a higher intake was associated with substantially reduced risk of coronary heart disease, primarily nonfatal cardiac events, among middle-aged persons.
Preserving Renal Function by Revascularization
Authors: M J Schreiber, M A Pohl, A C Novick
Journal: Annual Review of Medicine (1990)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Occurrence of wheezing and being overweight in the first three years of life in a birth cohort at high risk for the development of asthma/allergy
Authors: Z. Zhang, H. Lai, K.A. Roberg, M.D. Evans, R.E. Gangnon, E.L. Anderson, J.E. Gern, R.F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2005)
Suppression of Herpes Simplex Virus Type 1 (HSV-1)–induced Pneumonia in Mice by Inhibition of Inducible Nitric Oxide Synthase (iNOS, NOS2)
Authors: Heiko Adler, Janice L. Beland, Nadia C. Del-Pan, Lester Kobzik, Joanne P. Brewer, Thomas R. Martin, Ilonna J. Rimm
Journal: The Journal of Experimental Medicine (1997)

Intranasal Herpes simplex virus type 1 (HSV-1) infection of mice caused pneumonia. Manifestations of the disease included: histological pneumonitis, pulmonary influx of lymphocytes, decreased pulmonary compliance, and decreased survival. Immunohistochemical staining demonstrated iNOS induction and the nitrotyrosine antigen in the lungs of infected, but not uninfected mice, suggesting that nitric oxide contributes to the development of pneumonia. To elucidate the role of nitric oxide in the pathogenesis of HSV-1 pneumonia, infected mice were treated either with the inhibitor of nitric oxide synthase activity, NG-monomethyl-l-arginine (l-NMMA), or, as a control, with PBS or d-NMMA. l-NMMA treatment decreased the histological evidence of pneumonia and reduced the bronchoalveolar lavage lymphocyte number to one-quarter of the total measured in control-treated mice. l-NMMA treatment significantly improved survival and pulmonary compliance of HSV-1–infected mice. Strikingly, the l-NMMA–mediated suppression of pneumonia occurred despite the presence of a 17-fold higher pulmonary viral titer. Taken together, these data demonstrated a previously unrecognized role of nitric oxide in HSV-1–induced pneumonia. Of note, suppression of pneumonia occurred despite higher pulmonary virus content; therefore, our data suggest that HSV-1 pneumonia is due to aspects of the inflammatory response rather than to direct viral cytopathic effects.
High prevalence of autoantibodies to muscarinic-3 acetylcholine receptor in patients with juvenile-onset Sjogren syndrome
Authors: Y Nakamura, E Wakamatsu, I Matsumoto, M Tomiita, Y Kohno, M Mori, S Yokota, D Goto, S Ito, A Tsutsumi, T Sumida
Journal: Annals of the Rheumatic Diseases (2007)

Sjogren syndrome (SS) is an autoimmune disease characterised pathologically by lymphocytic infiltration into the lacrimal and salivary glands, and clinically by dry eyes and mouth. Lymphocytic infiltration is also found in the kidneys, lungs, thyroid, and liver. Immunohistochemical studies have shown that most infiltrating lymphocytes around the labial salivary and lacrimal glands and the kidneys are CD4-positive αβT cells.1 Candidate autoantigens recognised by T cells that infiltrate the labial salivary glands of SS have been analysed and Ro/SS-A 52 kDa,2 α-amylase, heat shock protein, and TCR BV63 have been identified, although Ro/SS-A 52 kDa reactive T cells were not increased in peripheral blood. …
Acute Occlusion of the Thoracic Aorta by Calcified Atherosclerosis
Authors: Afksendiyos Kalangos
Journal: Annals of Internal Medicine (1998)

Letters1 November 1998Acute Occlusion of the Thoracic Aorta by Calcified AtherosclerosisAfksendiyos Kalangos, MD, PhDAfksendiyos Kalangos, MD, PhDUniversity Cantonal Hospital of Geneva; Geneva, SwitzerlandAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-9-199811010-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:A 70-year-old woman presented to our emergency department with sudden onset of weakness in both legs, epigastric pain radiating to the back, nausea, and hematochezia. She smoked, had hypertension that had been controlled for 5 years with a β-blocker, and had a history of myocardial infarction and decreased femoral pulses with no claudication. Two days before hospitalization, an angiotensin-converting enzyme inhibitor was prescribed as an adjunct to the β-blocker because of blood pressure that had been fluctuating between 200/80 mm Hg and 220/90 mm Hg. She was drowsy and had a regular pulse rate (73 beats/min) and ...References1. Axilrod HD. Obstruction of the aortic isthmus by a calcified thrombus. Arch Pathol. 1946; 41:63-5. Google Scholar2. Taguschi JT. Obstruction by calcified thrombus of the aortic isthmus: a diagnostical roentgenological appearance. Am J Cardiol. 1963; 12:567-9. Google Scholar3. Kawahito K, Yamaguchi A, Adachi H, Mizuhara A, Murata S, Ino T. Acute occlusion of the descending thoracic aorta: report of a case. Jpn J Surg. 1996; 26:652-4. Google Scholar4. Froelich JJ, Drude L, Klose KJ. Schwere kalzifizierende Atherosklerose der thorakalen Aorta mit Symptomen einer Aortenistmusstenose. Radiologe. 1997; 37:173-6. Google Scholar5. Walter JF, Olcott CN, Mehigan JT, Gonzalez-Lavin L. Calcified aortic plug syndrome. J Can Assoc Radiol. 1981; 32:155-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: University Cantonal Hospital of Geneva; Geneva, Switzerland PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDo Not Blame the Arterial Catheter: A Case Report of Intraoperative Acute Leriche SyndromeBicyclic 5-6 Systems with One Bridgehead (Ring Junction) Nitrogen Atom: Two Extra Heteroatoms 0:2 1 November 1998Volume 129, Issue 9Page: 750-751KeywordsAortaAtherosclerosisBlood pressureDrugsHypertensionIschemiaMyocardial infarctionSurgeryThrombosisUrea Issue Published: 1 November 1998 Copyright & PermissionsCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Antigen affinity discrimination is an intrinsic function of the B cell receptor
Authors: Wanli Liu, Tobias Meckel, Pavel Tolar, Hae Won Sohn, Susan K. Pierce
Journal: The Journal of Experimental Medicine (2010)

Antibody affinity maturation, a hallmark of adaptive immune responses, results from the selection of B cells expressing somatically hypermutated B cell receptors (BCRs) with increased affinity for antigens. Despite the central role of affinity maturation in antibody responses, the molecular mechanisms by which the increased affinity of a B cell for antigen is translated into a selective advantage for that B cell in immune responses is incompletely understood. We use high resolution live-cell imaging to provide evidence that the earliest BCR-intrinsic events that follow within seconds of BCR–antigen binding are highly sensitive to the affinity of the BCR for antigen. High affinity BCRs readily form oligomers and the resulting microclusters grow rapidly, resulting in enhanced recruitment of Syk kinase and calcium fluxes. Thus, B cells are able to read the affinity of antigen by BCR-intrinsic mechanisms during the earliest phases of BCR clustering, leading to the initiation of B cell responses.