tbuckley/cabot-search huggingface dataset:
Generation of continuous large granular lymphocyte lines by interleukin 2 from the spleen cells of mice infected with Moloney leukemia virus. Involvement of interleukin 3.
Authors: M Hattori, T Sudo, M Iizuka, S Kobayashi, S Nishio, S Kano, N Minato
Journal: The Journal of Experimental Medicine (1987)

Continuous cell lines could be reproducibly established by culturing spleen cells from adult mice injected with MLV-producer cells or directly infected with Mo-MLV with rIL-2, whereas the culture of normal splenic cells with rIL-2 induced only transient and limited proliferation resulting in no such lines. All of the lines showed morphological characteristics as LGL with Thy-1+,Lyt-1-,L3T4-,Lyt-2-,AsGM1+,FcR gamma+ phenotype without exception, and most of them exhibited typical NK-patterned cytotoxicity. Analysis of reverse transcriptase activity of the culture supernatants as well as Southern hybridization of the DNA from the lines using an Mo-MLV-specific cDNA probe indicated no evidence of retroviral replication or proviral integration, suggesting that the generation of cell lines reflected a reactive process and viral infection was not directly responsible. It was subsequently revealed that Thy-1+,Lyt-1+,Lyt-2- spleen cells from mice infected with Mo-MLV in vivo spontaneously produced surprising amounts of IL-3 in vitro, leading to the possibility that IL-3 was responsible for the generation of lines. The possibility was directly supported by the observation that continuous lines with identical characteristics could be generated completely in vitro by sequential stimulation with rIL-3 and rIL-2 from normal spleen cells without any involvement of Mo-MLV. The C beta gene of TCR was shown to be rearranged in all the lines examined, indicating the LGL lines were all genetically committed to T cell lineage. Unlike the situation in normal splenic populations expanded by rIL-2, where the expression of IL-2-R was progressively lost, constitutive expression of high-affinity-IL-2-R was observed in all the lines and thus, this was considered to explain the unlimited proliferation of them in response to rIL-2 alone. These results suggested the probable role of IL-3 in the regulation of growth and differentiation of a set of LGL committed to T cell lineage. The possible implications of the phenomenon in the regulation of hematopoiesis as well as in the control of Mo-MLV-induced leukemogenesis were discussed.
Association of asthma and hay fever with irregular menstruation
Authors: C Svanes
Journal: Thorax (2005)

There is some evidence that asthmatic women are more likely to have abnormal sex hormone levels. A study was undertaken to determine whether asthma and allergy were associated with irregular menstruation in a general population, and the potential role of asthma medication for this association.A total of 8588 women (response rate 77%) participated in an 8 year follow up postal questionnaire study of participants of the ECRHS stage I in Denmark, Estonia, Iceland, Norway, and Sweden. Only non-pregnant women not taking exogenous sex hormones were included in the analyses (n = 6137).Irregular menstruation was associated with asthma (OR 1.54 (95% CI 1.11 to 2.13)), asthma symptoms (OR 1.47 (95% CI 1.16 to 1.86)), hay fever (OR 1.29 (95% CI 1.05 to 1.57)), and asthma preceded by hay fever (OR 1.95 (95% CI 1.30 to 2.96)) among women aged 26-42 years. This was also observed in women not taking asthma medication (asthma symptoms: OR 1.44 (95% CI 1.09 to 1.91); hay fever: OR 1.27 (95% CI 1.03 to 1.58); wheeze preceded by hay fever: OR 1.76 (95% CI 1.18 to 2.64)). Irregular menstruation was associated with new onset asthma in younger women (OR 1.58 (95% CI 1.03 to 2.42)) but not in women aged 42-54 years (OR 0.62 (95% CI 0.32 to 1.18)). The results were consistent across centres.Younger women with asthma and allergy were more likely to have irregular menstruation. This could not be attributed to current use of asthma medication. The association could possibly be explained by common underlying metabolic or developmental factors. The authors hypothesise that insulin resistance may play a role in asthma and allergy.
Dilemmas of low dosage glucocorticoid treatment in rheumatoid arthritis: considerations of timing
Authors: A. T MASI, G. P CHROUSOS
Journal: Annals of the Rheumatic Diseases (1997)

<h3>ABSTRACT</h3> Cell biologists can now build 3D models from segmentations of electron microscopy (EM) images, but accurate manual segmentation of densely-packed organelles across gigavoxel image volumes is infeasible. Here, we introduce 2D-3D neural network ensembles that produce dense cellular segmentations at scale, with accuracy levels that outperform baseline methods and approach those of human annotators.
Tripotassium dicitrato bismuthate (TDB) versus two different dosages of cimetidine in the treatment of resistant duodenal ulcers.
Authors: G B Porro, F Parente, M Lazzaroni
Journal: Gut (1987)

The use of tripotassium dicitrato bismuthate (TDB) has been suggested recently for cimetidine resistant duodenal ulcers. This study compares the efficacy of TDB with two different cimetidine dosages in the treatment of duodenal ulcer patients who failed to respond to an eight week therapy with H2-blockers. Fifty two patients (40 men, 12 women) were randomly allocated to one of the following three oral regimens: (1) TDB 120 mg quid, (2) cimetidine 400 mg tid, (3) cimetidine 400 mg with meals plus 800 mg at bedtime. Endoscopy was carried out after four weeks; if the ulcer had not healed patients continued with the same treatment for a further four week period when they were endoscopically reassessed. After four weeks similar percentages of ulcer healing were registered in the two cimetidine schedules (39% with 1.2 g and 44% with 2 g), whereas TDB resulted in a significantly higher healing rate (82%) compared with cimetidine 1.2 g (p = 0.01) and with cimetidine 2 g (p = 0.025). After eight weeks the cumulative percentages of healing were 65% on cimetidine 1.2 g, 75% on cimetidine 2 g, and 94% on TDB (TDB v cimetidine 1.2 p = 0.042). These results confirm previous data that resistant duodenal ulcers are more responsive to an agent which strengthens the mucosal defences than to antisecretory compounds.
Influenza virus subtype-specific cytotoxic T lymphocytes lyse target cells coated with a protein produced in E. coli.
Authors: A Yamada, J F Young, F A Ennis
Journal: The Journal of Experimental Medicine (1985)

We have tested the ability of the c13 protein, which is a hybrid protein of the first 81 amino acids of the viral nonstructural protein (NS1) and the HA2 subunit of viral hemagglutination produced in E. coli, to render target cells susceptible to the lytic activity of influenza virus-specific cytotoxic T lymphocytes (CTL). The results showed that P815 cells coated with c13 protein were lysed by PR8 virus-induced secondary CTL derived from BALB/c mice. Cold-target inhibition tests clearly demonstrated that c13 protein-coated P815 cells were recognized by an H1 subtype-specific CTL population. Furthermore, PR8 virus-induced CTL derived from C3H mice did not lyse c13 protein-coated P815 cells, suggesting that c13 protein was recognized by CTL in conjunction with H-2d products. These findings suggest that this protein interacts with the cellular plasma membrane and makes target cells recognizable by H-2-restricted, influenza virus subtype-specific CTL.
1360 PEGYLATED INTERFERON-LAMBDA (PEGIFN-λ) SHOWS SUPERIOR VIRAL RESPONSE WITH IMPROVED SAFETY AND TOLERABILITY VERSUS PEGIFNα-2A IN HCV PATIENTS (Gl/2/3/4): EMERGE PHASE IIB THROUGH WEEK 12
Authors: S. Zeuzem, S. Arora, B. Bacon, T. Box, M. Charlton, M. Diago, D. Dieterich, R. Esteban Mur, G. Everson, M. Fallón, P. Ferenci, R. Flisiak, J. George, R. Ghalib, N. Gitlin, A. Gladysz, S. Gordon, S. Greenbloom, T. Hassanein, I. Jacobson, L. Jeffers, K. Kowdley, E. Lawitz, S. Lee, B. Leggett, S. Lueth, D. Nelson, P. Pockros, M. Rodriguez-Torres, V. Rustgi, L. Serfaty, M. Sherman, M. Shiffman, R. Sola, M. Sulkowski, H. Vargas, J. Vierling, B. Yoffe, L. Ishak, D. Fontana, D. Xu, J. Lester, T. Gray, A. Horga, J. Hillson, E. Ramos, J.C. Lopez-Talavera, A. Muir
Journal: Journal of Hepatology (2011)
Limited effects of high-dose intravenous immunoglobulin (IVIG) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies
Authors: S. B. Helmers, M. Dastmalchi, H. Alexanderson, I. Nennesmo, M. Esbjornsson, B. Lindvall, I. E Lundberg
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> The study was conducted with the aim of achieving an improved understanding of the molecular mechanisms of high-dose intravenous immunoglobulin (IVIG) in inflammatory myopathies by investigating the effects on muscle function and immunological molecules in skeletal muscle of polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM) patients. <h3>Methods:</h3> Thirteen treatment-resistant patients, 6 PM, 4 DM, 2 IBM and 1 juvenile DM, were treated with 2 g/kg of IVIG, three times at monthly intervals. Functional Index in Myositis and serum creatinine kinase (CK) levels were determined, and muscle biopsies were performed before treatment and after the third IVIG infusion. Immunological molecules were also studied in biopsies taken 24–48 h after the first infusion. <h3>Results:</h3> Improved muscle function was observed in three patients (1 PM, 1 DM and 1 IBM) and CK levels decreased in five. T cells, macrophages, major histocompatibility complex (MHC) class I antigen on muscle fibres, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression and membranolytic attack complex (MAC) deposits on capillaries were present to an equal degree in biopsies before and after IVIG treatment. No correlation between the clinical response and molecular changes was found. <h3>Conclusions:</h3> The clinical effects of high-dose IVIG on muscle function in patients with refractory inflammatory active myositis did not correspond to effects on any of the investigated molecules in our study. T cells, macrophages, phenotypical changes in muscle fibres and endothelial cell activation were still present after treatment. These observations question a role for IVIG as an immune-modulating therapy in patients with inflammatory myopathies.
Endothelium-Derived Hyperpolarizing Factor in Human Internal Mammary Artery Is 11,12-Epoxyeicosatrienoic Acid and Causes Relaxation by Activating Smooth Muscle BK <sub>Ca</sub> Channels
Authors: Stephen L. Archer, Ferrante S. Gragasin, Xichen Wu, Shaohua Wang, Sean McMurtry, Daniel H. Kim, Michael Platonov, Arvind Koshal, Kyoko Hashimoto, William B. Campbell, J.R. Falck, Evangelos D. Michelakis
Journal: Circulation (2003)

Background— Left internal mammary arteries (LIMAs) synthesize endothelium-derived hyperpolarizing factor (EDHF), a short-lived K + channel activator that persists after inhibition of nitric oxide (NO) and prostaglandin synthesis. EDHF hyperpolarizes and relaxes smooth muscle cells (SMCs). The identity of EDHF in humans is unknown. We hypothesized that EDHF (1) is 11,12-epoxyeicosatrienoic acid (11,12-EET); (2) is generated by cytochrome P450-2C, CYP450-2C; and (3) causes relaxation by opening SMC large-conductance Ca 2+ -activated K + channels (BK Ca ). Methods and Results— The identity of EDHF and its mechanism of action were assessed in 120 distal human LIMAs and 20 saphenous veins (SVs) obtained during CABG. The predominant EET synthesized by LIMAs is 11,12-EET. Relaxations to exogenous 11,12-EET and endogenous EDHF are of similar magnitudes. Inhibition of EET synthesis by chemically distinct CYP450 inhibitors (17-octadecynoic acid, N -methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide), or a selective EET antagonist (4,15-epoxyeicosa-5( Z )-enoic acid) impairs EDHF relaxation. 11,12-EET activates a BK Ca current and hyperpolarizes LIMA SMCs. Inhibitors of BK Ca but not inward-rectifier or small-conductance K Ca channels abolish relaxation to endogenous EDHF and exogenous 11,12-EET. BK Ca and CYP450-2C mRNA and proteins are more abundant in LIMAs than in SVs, perhaps explaining the lack of EDHF activity of the SV. Laser capture microdissection and quantitative RT-PCR demonstrate that BK Ca channels are primarily in vascular SMCs, whereas the CYP450-2C enzyme is present in both the endothelium and SMCs. Conclusions— In human LIMAs, EDHF is 11,12-EET produced by an EDHF synthase CYP450-2C and accounting for ≈40% of net endothelial relaxation. 11,12-EET causes relaxation by activating SMC BK Ca channels.
Naturally Occurring Higher Hemoglobin Concentration Does Not Increase Mortality among Hemodialysis Patients
Authors: David A. Goodkin, Douglas S. Fuller, Bruce M. Robinson, Christian Combe, Richard Fluck, David Mendelssohn, Tadao Akizawa, Ronald L. Pisoni, Friedrich K. Port
Journal: Journal of the American Society of Nephrology (2010)

A small percentage of hemodialysis patients maintain higher hemoglobin concentrations without transfusion or erythropoietic therapy. Because uncertainty exists regarding the effects of higher hemoglobin concentration on mortality and quality of life among hemodialysis patients, studying this group of patients with sufficient endogenous erythropoietin may provide additional insights. The prospective, observational Dialysis Outcomes and Practice Patterns Study provides an opportunity to investigate this group. Among 29,796 patients in 12 nations, 545 (1.8%) maintained hemoglobin concentrations >12 g/dl for 4 months without erythropoietic support. This subset tended to be male, to have a longer duration of end-stage renal disease, and to not dialyze via a catheter. Cystic disease as the underlying cause of renal failure was over-represented in this group but was present in only 25%. Lung disease, smoking, and cardiovascular disease were associated with increased likelihood of naturally higher hemoglobin concentration. Quality-of-life scores were not higher among this subset compared with the other patients. Unadjusted mortality risk for patients with hemoglobin >12 g/dl and no erythropoietic therapy was lower than for the other patients, but after thorough adjustment for case mix, there was no difference between groups (relative risk, 0.98; 95% CI 0.80 to 1.19). These data show that naturally occurring hemoglobin concentration >12 g/dl does not associate with increased mortality among hemodialysis patients.
Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center
Authors: Yasuhiro Oki, Hagop M. Kantarjian, Xian Zhou, Jorge Cortes, Stefan Faderl, Srdan Verstovsek, Susan O'Brien, Charles Koller, Miloslav Beran, B. Nebiyou Bekele, Sherry Pierce, Deborah Thomas, Farhad Ravandi, William G. Wierda, Francis Giles, Alessandra Ferrajoli, Elias Jabbour, Michael J. Keating, Carlos E. Bueso-Ramos, Elihu Estey, Guillermo Garcia-Manero
Journal: Blood (2005)
Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompatibility Complex Class I Products and Peripheral CD8+ T Cell Tolerance
Authors: Laura Bonifaz, David Bonnyay, Karsten Mahnke, Miguel Rivera, Michel C. Nussenzweig, Ralph M. Steinman
Journal: The Journal of Experimental Medicine (2002)

To identify endocytic receptors that allow dendritic cells (DCs) to capture and present antigens on major histocompatibility complex (MHC) class I products in vivo, we evaluated DEC-205, which is abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein, when chemically coupled to monoclonal αDEC-205 antibody, was presented by CD11c+ lymph node DCs, but not by CD11c− cells, to OVA-specific, CD4+ and CD8+ T cells. Receptor-mediated presentation was at least 400 times more efficient than unconjugated OVA and, for MHC class I, the DCs had to express transporter of antigenic peptides (TAP) transporters. When αDEC-205:OVA was injected subcutaneously, OVA protein was identified over a 4–48 h period in DCs, primarily in the lymph nodes draining the injection site. In vivo, the OVA protein was selectively presented by DCs to TCR transgenic CD8+ cells, again at least 400 times more effectively than soluble OVA and in a TAP-dependent fashion. Targeting of αDEC-205:OVA to DCs in the steady state initially induced 4–7 cycles of T cell division, but the T cells were then deleted and the mice became specifically unresponsive to rechallenge with OVA in complete Freund's adjuvant. In contrast, simultaneous delivery of a DC maturation stimulus via CD40, together with αDEC-205:OVA, induced strong immunity. The CD8+ T cells responding in the presence of agonistic αCD40 antibody produced large amounts of interleukin 2 and interferon γ, acquired cytolytic function in vivo, emigrated in large numbers to the lung, and responded vigorously to OVA rechallenge. Therefore, DEC-205 provides an efficient receptor-based mechanism for DCs to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.
Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease
Authors: Benjamin I. Goldstein, Mercedes R. Carnethon, Karen A. Matthews, Roger S. McIntyre, Gregory E. Miller, Geetha Raghuveer, Catherine M. Stoney, Hank Wasiak, Brian W. McCrindle
Journal: Circulation (2015)

In the 2011 “Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents,” several medical conditions among youth were identified that predispose to accelerated atherosclerosis and early cardiovascular disease (CVD), and risk stratification and management strategies for youth with these conditions were elaborated. Major depressive disorder (MDD) and bipolar disorder (BD) among youth satisfy the criteria set for, and therefore merit inclusion among, Expert Panel tier II moderate-risk conditions. The combined prevalence of MDD and BD among adolescents in the United States is ≈10%, at least 10 times greater than the prevalence of the existing moderate-risk conditions combined. The high prevalence of MDD and BD underscores the importance of positioning these diseases alongside other pediatric diseases previously identified as moderate risk for CVD. The overall objective of this statement is to increase awareness and recognition of MDD and BD among youth as moderate-risk conditions for early CVD. To achieve this objective, the primary specific aims of this statement are to (1) summarize evidence that MDD and BD are tier II moderate-risk conditions associated with accelerated atherosclerosis and early CVD and (2) position MDD and BD as tier II moderate-risk conditions that require the application of risk stratification and management strategies in accordance with Expert Panel recommendations. In this scientific statement, there is an integration of the various factors that putatively underlie the association of MDD and BD with CVD, including pathophysiological mechanisms, traditional CVD risk factors, behavioral and environmental factors, and psychiatric medications.
Naltrexone for the Treatment of Amphetamine Dependence: A Randomized, Placebo-Controlled Trial
Authors: Nitya Jayaram-Lindström, Anders Hammarberg, Olof Beck, Johan Franck
Journal: American Journal of Psychiatry (2008)

Currently there is no approved pharmacotherapy for amphetamine dependence. Recent human laboratory studies have demonstrated that naltrexone modulates some of the reinforcing effects of amphetamine. The aim of this study was to investigate the efficacy of naltrexone in comparison with placebo in reducing relapse to amphetamine use in amphetamine-dependent patients.Eighty patients who met DSM-IV criteria for amphetamine dependence were randomized to 12 weeks of double-blind naltrexone (50 mg) or placebo treatment. Patients visited the clinic twice weekly to receive medication and relapse prevention therapy and leave urine samples, which were analyzed for drug toxicology and for assessing adherence to medication via detection of naltrexone's metabolite (6-beta-naltrexol). The main outcome measure was abstinence from amphetamine use, as indicated by the total number of negative amphetamine urine samples during 12 weeks of treatment. All missing urine samples were defined for the analysis as positive for amphetamine.Overall, 55 patients (68.8%) completed the trial. The intention-to-treat analysis showed that the naltrexone group had a significantly higher number of amphetamine-negative urine samples compared with the placebo group. Survival analyses showed that the treatment groups differed in rate of continuous abstinence, in both the intention-to-treat and completer samples, in favor of naltrexone treatment. There was a significant reduction in craving levels and self-reported consumption of amphetamine in the naltrexone group compared with the placebo group. Treatment with naltrexone was well tolerated in this sample.This trial demonstrated the efficacy of naltrexone in reducing amphetamine use in amphetamine-dependent individuals.
Lysyl Oxidase Regulates Breast Cancer Cell Migration and Adhesion through a Hydrogen Peroxide–Mediated Mechanism
Authors: Stacey L. Payne, Ben Fogelgren, Angela R. Hess, Elisabeth A. Seftor, Elizabeth L. Wiley, Sheri F.T. Fong, Katalin Csiszar, Mary J.C. Hendrix, Dawn A. Kirschmann
Journal: Cancer Research (2005)

Abstract We have previously shown that lysyl oxidase (LOX) mRNA is up-regulated in invasive breast cancer cells and that catalytically active LOX facilitates in vitro cell invasion. Here we validate our in vitro studies by showing that LOX expression is up-regulated in distant metastatic breast cancer tissues compared with primary cancer tissues. To elucidate the mechanism by which LOX facilitates cell invasion, we show that catalytically active LOX regulates in vitro motility/migration and cell-matrix adhesion formation. Treatment of the invasive breast cancer cell lines, Hs578T and MDA-MB-231, with β-aminopropionitrile (βAPN), an irreversible inhibitor of LOX catalytic activity, leads to a significant decrease in cell motility/migration and adhesion formation. Conversely, poorly invasive MCF-7 cells expressing LOX (MCF-7/LOX32-His) showed an increase in migration and adhesion that was reversible with the addition of βAPN. Moreover, a decrease in activated focal adhesion kinase (FAK) and Src kinase, key proteins involved in adhesion complex turnover, was observed when invasive breast cancer cells were treated with βAPN. Additionally, FAK and Src activation was increased in MCF-7/LOX32-His cells, which was reversible on βAPN treatment. Hydrogen peroxide was produced as a by-product of LOX activity and the removal of hydrogen peroxide by catalase treatment in invasive breast cancer cells led to a dose-dependent loss in Src activation. These results suggest that LOX facilitates migration and cell-matrix adhesion formation in invasive breast cancer cells through a hydrogen peroxide–mediated mechanism involving the FAK/Src signaling pathway. These data show the need to target LOX for treatment of aggressive breast cancer. (Cancer Res 2005; 65(24): 11429-36)
Virulence genotype and nematode-killing properties of extra-intestinal Escherichia coli producing CTX-M β-lactamases
Authors: J.-P. Lavigne, A.-B. Blanc-Potard, G. Bourg, J. Moreau, C. Chanal, N. Bouziges, D. O'Callaghan, A. Sotto
Journal: Clinical Microbiology and Infection (2006)