tbuckley/cabot-search huggingface dataset:
Histamine stimulates the proliferation of human articular chondrocytes in vitro and is expressed by chondrocytes in osteoarthritic cartilage
Authors: L C Tetlow, D E Woolley
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objectives:</b> To determine the effects of histamine on the proliferative rate of human articular chondrocytes (HAC) in vitro, and to demonstrate whether HAC in osteoarthritic (OA) cartilage express histamine and histidine decarboxylase (HDC). <b>Methods:</b> HAC in vitro were incubated with and without histamine in 96 well culture plates and the extent of cell proliferation was determined using the naphthol blue-black method. Histamine effects were analysed with the histamine H<sub>1</sub> and H<sub>2</sub> receptor antagonists, mepyramine and ranitidine, respectively. Rabbit polyclonal antibodies and alkaline phosphatase conjugated secondary antibodies were used, and histamine and HDC were demonstrated by immunohistochemistry in OA cartilage tissues. <b>Results:</b> Histamine stimulated the proliferation of HAC in culture. This stimulation was blocked by the addition of mepyramine, but not ranitidine, suggesting that the effect is mediated through H<sub>1</sub> histamine receptors. The addition of α-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase (the enzyme responsible for histamine production), reduced the rate of proliferation of HAC. Both histamine and histidine decarboxylase were demonstrated in chondrocytes of OA cartilage by immunohistochemistry. <b>Conclusion:</b> Changes induced by histamine in the proliferative rate of HAC may contribute to the formation of chondrocyte clusters associated with OA cartilage; an observation supported by the demonstration of histamine and HDC expression by chondrocytes of OA cartilage in situ.
Human intestinal Vdelta1+ lymphocytes recognize tumor cells of epithelial origin.
Authors: M J Maeurer, D Martin, W Walter, K Liu, L Zitvogel, K Halusczcak, H Rabinowich, R Duquesnoy, W Storkus, M T Lotze
Journal: The Journal of Experimental Medicine (1996)

gammadelta T cells can be grouped into discrete subsets based upon their expression of T cell receptor (TCR) variable (V) region families, their tissue distribution, and their specificity. Vdelta2+ T cells constitute the majority of gammadelta T cells in peripheral blood whereas Vdelta1+T cells reside preferentially in skin epithelium and in the intestine. gammadelta T cells are envisioned as first line host defense mechanisms capable of providing a source of immune effector T cells and immunomodulating cytokines such as interleukin (IL) 4 or interferon (IFN) gamma. We describe here the fine specificity of three distinct gammadelta+ tumor-infiltrating lymphocytes (TIL) obtained from patients with primary or metastatic colorectal cancer, that could be readily expanded in vitro in the presence of IL-1beta and IL-7. Irrespective of donor, these individual gammadelta T cells exhibited a similar pattern of reactivity defined by recognition of autologous and allogeneic colorectal cancer cells, renal cell cancer, pancreatic cancer, and a freshly isolated explant from human intestine as measured by cytolytic T cell responses and by IFN-gamma release. In contrast, tumors of alternate histologies were not lysed, including lung cancer, squamous cell cancer, as well as the natural/lymphocyte-activated killer cell-sensitive hematopoietic cell lines T2, C1R, or Daudi. The cell line K562 was only poorly lysed when compared with colorectal cancer targets. Target cell reactivity mediated by Vdelta1+ T cells was partially blocked with Abs directed against the TCR, the beta2 or beta7 integrin chains, or fibronectin receptor. Marker analysis using flow cytometry revealed that all three gammadelta T cell lines exhibit a similar phenotype. Analysis of the gammadelta TCR junctional suggested exclusive usage of the Vdelta1/Ddelta3/Jdelta1 TCR segments with extensive (&amp;lt; or = 29 bp) N/P region diversity. T cell recognition of target cells did not appear to be a major histocompatibility complex restricted or to be correlated with target cell expression of heat-shock proteins. Based on the ability of some epithelial tumors, including colorectal, pancreatic, and renal cell cancers to effectively cold target inhibit the lysis of colorectal cancer cell lines by these Vdelta1+ T cell lines, we suggest that intestinal Vdelta1+ T cell lines, we suggest that intestinal Vdelta1+ T cells are capable of recognizing cell surface Ag(s) shared by tumors of epithelial origin.
Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial
Authors: Greet Hermans, Michael P Casaer, Beatrix Clerckx, Fabian Güiza, Tine Vanhullebusch, Sarah Derde, Philippe Meersseman, Inge Derese, Dieter Mesotten, Pieter J Wouters, Sophie Van Cromphaut, Yves Debaveye, Rik Gosselink, Jan Gunst, Alexander Wilmer, Greet Van den Berghe, Ilse Vanhorebeek
Journal: The Lancet Respiratory Medicine (2013)
Apoptosis and Programmed Cell Death in Immunity
Authors: J. John Cohen, Richard C. Duke, Valerie A. Fadok, Karen S. Sellins
Journal: Annual Review of Immunology (1992)

Death of some cells in the mammalian body is clearly programmed. In the immune system there are many examples of programmed cell death, during development of lymphocytes as well as at later stages, after interaction with antigen. Many of these examples display the morphology of apoptosis: They undergo shrinkage and zeiosis, the nucleus collapses, and chromatin is cleaved into nucleosomal fragments. The cell is rapidly recognized by phagocytes and disposed of without releasing its contents. In some but not all cases of apoptosis, new macromolecular synthesis is required. Cytotoxic T cells induce changes in their targets that are morphologically apoptotic. The mechanism ofapoptosis is currently under active investigation.
Secondhand smoke and incidence of dental caries in deciduous teeth among children in Japan: population based retrospective cohort study
Authors: Shiro Tanaka, Maki Shinzawa, Hironobu Tokumasu, Kahori Seto, Sachiko Tanaka, Koji Kawakami
Journal: BMJ (2015)

<b>Study question</b> Does maternal smoking during pregnancy and exposure of infants to tobacco smoke at age 4 months increase the risk of caries in deciduous teeth? <b>Methods</b> Population based retrospective cohort study of 76 920 children born between 2004 and 2010 in Kobe City, Japan who received municipal health check-ups at birth, 4, 9, and 18 months, and 3 years and had information on household smoking status at age 4 months and records of dental examinations at age 18 months and 3 years. Smoking during pregnancy and exposure of infants to secondhand smoke at age 4 months was assessed by standardised parent reported questionnaires. The main outcome measure was the incidence of caries in deciduous teeth, defined as at least one decayed, missing, or filled tooth assessed by qualified dentists without radiographs. Cox regression was used to estimate hazard ratios of exposure to secondhand smoke compared with having no smoker in the family after propensity score adjustment for clinical and lifestyle characteristics. <b>Study answer and limitations</b> Prevalence of household smoking among the 76 920 children was 55.3% (n=42 525), and 6.8% (n=5268) had evidence of exposure to tobacco smoke. A total of 12 729 incidents of dental caries were observed and most were decayed teeth (3 year follow-up rate 91.9%). The risk of caries at age 3 years was 14.0% (no smoker in family), 20.0% (smoking in household but without evidence of exposure to tobacco smoke), and 27.6% (exposure to tobacco smoke). The propensity score adjusted hazard ratios of the two exposure groups compared with having no smoker in the family were 1.46 (95% confidence interval 1.40 to 1.52) and 2.14 (1.99 to 2.29), respectively. The propensity score adjusted hazard ratio between maternal smoking during pregnancy and having no smoker in the family was 1.10 (0.97 to 1.25). <b>What this study adds</b> Exposure to tobacco smoke at 4 months of age was associated with an approximately twofold increased risk of caries, and the risk of caries was also increased among those exposed to household smoking, by 1.5-fold, whereas the effect of maternal smoking during pregnancy was not statistically significant. <b>Funding, competing interests, data sharing</b> This study was supported by a grant in aid for scientific research 26860415. The authors have no competing interests or additional data to share.
Vitamin E: A Role in Signal Transduction
Authors: Jean-Marc Zingg
Journal: Annual Review of Nutrition (2015)

Vitamin E modulates the activity of several signal transduction enzymes with consequent alterations of gene expression. At the molecular level, vitamin E may directly bind to these enzymes and compete with their substrates, or it may change their activity by redox regulation. The translocation of several of these enzymes to the plasma membrane is regulated by vitamin E, suggesting the modulation of protein-membrane interactions as a common mechanism for vitamin E action. Enzyme-membrane interactions can be affected by vitamin E by interference with binding to specific membrane lipids or by altering cellular structures such as membrane microdomains (lipid rafts). Moreover, competition by vitamin E for common binding sites within lipid transport proteins may alter the traffic of lipid mediators and thus affect their signaling and enzymatic conversion. In this review, the main effects of vitamin E on enzymes involved in signal transduction are summarized and possible molecular mechanisms leading to enzyme modulation are evaluated.
Lack of EP4 receptors on bone marrow-derived cells enhances inflammation in atherosclerotic lesions
Authors: E. H. C. Tang, K. Shimizu, T. Christen, V. Z. Rocha, E. Shvartz, Y. Tesmenitsky, G. Sukhova, G.-P. Shi, P. Libby
Journal: Cardiovascular Research (2010)

prostaglandin E(2), by ligation of its receptor EP4, suppresses the production of inflammatory cytokines and chemokines in macrophages in vitro. Thus, activation of EP4 may constitute an endogenous anti-inflammatory pathway. This study investigated the role of EP4 in atherosclerosis in vivo, and particularly its impact on inflammation.Ldlr(-/-) mice transplanted with EP4(+/+) or EP4(-/-) bone marrow consumed a high-fat diet for 5 or 10 weeks. Allogenic bone marrow transplantation promoted exacerbation of atherosclerosis irrespective of EP4 genotype, compatible with prior observations of exacerbated atherogenesis by allogenicity. EP4 deficiency had little effect on plaque size or morphology in early atherosclerosis, but at the later time point, mice deficient in EP4 displayed enhanced inflammation in their atherosclerotic plaques. Expression of monocyte chemoattractant protein-1 and interferon-γ inducible protein 10 increased, and there was a corresponding increase in macrophage and T-cell infiltration. These plaques also contained fewer smooth muscle cells. Despite these changes, mice deficient in EP4 in bone marrow-derived cells at an advanced stage had similar lesion size (in both aorta and aortic root) as mice with EP4.this study shows that in advanced atherosclerosis, EP4 deficiency did not alter atherosclerotic lesion size, but yielded plaques with exacerbated inflammation and altered lesion composition.
The expectancies that govern the P300 amplitude are mostly automatic and unconscious
Authors: W. Sommer, H. Leuthold, J. Matt
Journal: Behavioral and Brain Sciences (1998)

We argue that probability effects on P300 amplitude are the product of an automatic frequency detector not subject to voluntary control and relatively inaccessible to consciousness. “Expectancies” related to P300 therefore appear to be passive, perceptual ones. If probability-based expectancies do become conscious, they are inversely related to P300, supporting the view of Donchin &amp; Coles (1988).
Higher-than-expected Severe (Grade 3–4) Late Urinary Toxicity After Postprostatectomy Hypofractionated Radiotherapy: A Single-institution Analysis of 1176 Patients
Authors: Cesare Cozzarini, Claudio Fiorino, Chiara Deantoni, Alberto Briganti, Andrei Fodor, Mariangela La Macchia, Barbara Noris Chiorda, Paola Maria Vittoria Rancoita, Nazareno Suardi, Flavia Zerbetto, Riccardo Calandrino, Francesco Montorsi, Nadia Di Muzio
Journal: European Urology (2014)
Loss of Heterozygosity Patterns Provide Fingerprints for Genetic Heterogeneity in Multistep Cancer Progression of Tobacco Smoke–Induced Non–Small Cell Lung Cancer
Authors: Hongjie Pan, Joseph Califano, Jose F. Ponte, Andrea L. Russo, Kuang-hung Cheng, Arunthathi Thiagalingam, Pratima Nemani, David Sidransky, Sam Thiagalingam
Journal: Cancer Research (2005)

Dilution end point loss of heterozygosity (LOH) analysis, a novel approach for the analysis of LOH, was used to evaluate allelic losses with the use of 21 highly polymorphic microsatellite markers at nine chromosomal sites most frequently affected in smoking-related non-small cell lung cancers. Allelotyping was done for bronchial epithelial cells and matching blood samples from 23 former and current smokers and six nonsmokers as well as in 33 adenocarcinomas and 25 squamous cell carcinomas (SCC) and corresponding matching blood from smokers. Major conclusions from these studies are as follows: (a) LOH at chromosomal sites 8p, 9p, 11q, and 13q (P >0.05, Fisher's exact test) are targeted at the early stages, whereas LOH at 1p, 5q, 17p, and 18q (P <0.05, Fisher's exact test) occur at the later stages of non-small cell lung cancer progression; (b) LOH at 1p, 3p, 5q, 8p, 9p, 11q, 13q, 17p, and 18q occurs in over 45% of the tobacco smokers with SCC and adenocarcinoma; (c) compared with bronchial epithelial cells from smokers, there is a significantly higher degree of LOH at 1p, 5q, and 18q in adenocarcinoma and at 1p, 3p, and 17p in SCC (P <0.05, Fisher's exact test). We propose that lung cancer progression induced by tobacco smoke occurs in a series of target gene inactivations/activations in defined modules of a global network. The gatekeeper module consists of multiple alternate target genes, which is inclusive of but not limited to genes localized to chromosomal loci 8p, 9p, 11q, and 13q.
Updated Nomogram Predicting Lymph Node Invasion in Patients with Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection: The Essential Importance of Percentage of Positive Cores
Authors: Alberto Briganti, Alessandro Larcher, Firas Abdollah, Umberto Capitanio, Andrea Gallina, Nazareno Suardi, Marco Bianchi, Maxine Sun, Massimo Freschi, Andrea Salonia, Pierre I. Karakiewicz, Patrizio Rigatti, Francesco Montorsi
Journal: European Urology (2011)
HER2 Status and Efficacy of Adjuvant Anthracyclines in Early Breast Cancer: A Pooled Analysis of Randomized Trials
Authors: Alessandra Gennari, Maria Pia Sormani, Paolo Pronzato, Matteo Puntoni, Mariantonietta Colozza, Ulrich Pfeffer, Paolo Bruzzi
Journal: JNCI Journal of the National Cancer Institute (2007)

Adjuvant chemotherapy with anthracyclines improves disease-free and overall survival compared with non–anthracycline-based adjuvant chemotherapy regimens in the treatment of early breast cancer. The role of HER2 status as a marker of anthracycline responsiveness has been explored by subset analyses within randomized clinical trials, with inconsistent results. We performed a pooled analysis of the interaction between HER2 status and the efficacy of adjuvant anthracyclines based on the published subset data. We searched literature databases to identify randomized trials that compared anthracycline-based with non–anthracycline-based adjuvant chemotherapy regimens in the treatment of early breast cancer and reported efficacy data according to HER2 status. Log hazard ratios (HRs) for disease-free and overall survival were pooled across the studies according to HER2 status by inverse variance weighting. A pooled test for treatment by HER2 status interaction was performed by weighted linear meta-regression. All statistical tests were two-sided. Eight studies (with 6564 randomly assigned patients, of whom 5354 had HER2 status information available) were eligible for this analysis. In HER2 -positive disease (n = 1536 patients), anthracyclines were superior to non–anthracycline-based regimens in terms of disease-free (pooled HR of relapse = 0.71; 95% confidence interval [CI] = 0.61 to 0.83; P < .001) and overall (pooled HR of death from any cause = 0.73; 95% CI = 0.62 to 0.85; P < .001) survival. In HER2 -negative disease (n = 3818 patients), anthracyclines did not improve disease-free (HR = 1.00; 95% CI = 0.90 to 1.11; P = .75) or overall (HR = 1.03; 95% CI = 0.92 to 1.16; P = .60) survival. The test for treatment by HER2 status interaction yielded statistically significant results: for disease-free survival, the chi-square statistic for interaction was 13.7 ( P < .001), and for overall survival, it was 12.6 ( P < .001). The added benefits of adjuvant chemotherapy with anthracyclines appear to be confined to women who have HER2 overexpressed or amplified breast tumors.
Long-Acting Psychotraumatic Properties of a Cardiac Arrest Experience
Authors: Karl-Heinz Ladwig, Andreas Schoefinius, Gerhard Dammann, Reinhold Danner, Rolf Gürtler, Robert Herrmann
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Progress in resuscitation medicine allows an increasing proportion of patients to survive an out-of-hospital cardiac arrest. However, little is known about long-term adaptation to the vital breakdown. The present study assessed the long-term prevalence and severity of emotional disability of cardiac arrest survivors and ascertained whether survivors suffer from recurrent and intrusive recollections of the cardiac arrest. METHOD: Follow-up analysis was performed on all cardiac arrest survivors discharged from the hospital over a 5-year interval (1990–1994) in a defined inner city and suburban area. From 118 initially hospitalized cardiac arrest survivors, 45 patients were discharged alive from the hospital. After a mean follow-up period of 39 months (range=22–64), 25 patients exhibited sufficient cerebral performance for psychodiagnostic assessment; 21 patients were assessed. RESULTS: Despite an impaired ability to concentrate, cardiac arrest survivors had levels of psychological adjustment at follow-up that were similar to those of 35 cardiac patients whose clinical course was not complicated by cardiac arrest. However, the diagnosis of psychotraumatic symptoms in cardiac arrest survivors led to a sharp separation between favorable and nonfavorable outcome in affective regulation and level of functioning. Of the cardiac arrest patients, those with high scores of intrusion and avoidance (N=8) reported an enduring sense of demoralization with significantly more somatic complaints, depression, anxiety, lack of confidence in the future, and narrowing of social activities than those with low scores (N=11). Long-acting sedation at illness onset significantly predicted a favorable outcome. CONCLUSIONS: This study provides the first empirical evidence that the application of the posttraumatic stress disorder paradigm in the long-term evaluation of cardiac arrest survivors significantly contributes to defining a patient population at high risk for serious emotional disability.
Psychiatric Assessment of 30 Chronic Users of Cannabis and 30 Matched Controls
Authors: MICHAEL H. BEAUBRUN, FRANK KNIGHT
Journal: American Journal of Psychiatry (1973)

A study done in Jamaica of 30 chronic cannabis smokers (use for at least seven years) and 30 matched controls revealed no significant differences between the two groups in the incidence of mental illness or of abnormalities of mood, thought, or behavior. Nor did the groups differ significantly with regard to criminal records, use of other drugs, or upward or downward movement in social or economic position.
Crystal Structure of the Human Natural Killer Cell Activating Receptor KIR2DS2 (CD158j)
Authors: Xavier Saulquin, Louis N. Gastinel, Eric Vivier
Journal: The Journal of Experimental Medicine (2003)

Killer cell Ig-like receptors (KIRs) regulate the function of human natural killer and T cell subsets. A feature of the KIR locus is the clustering of homologous genes encoding for inhibitory and activating KIR. Inhibitory and activating KIR differ for ligand specificities and/or affinities. In particular, we show here with KIR tetramers that activating KIR2DS2 does not bind HLA-Cw3 molecules recognized by inhibitory KIR2DL2, despite 99% extracellular amino acid identity. We also report the 2.3-Å structure of KIR2DS2, which reveals subtle displacements of two residues (Tyr45 and Gln71) involved in the interaction of KIR2DL2 with HLA-Cw3. These results show that KIR molecules cannot tolerate any variability in their three-dimensional structure without altering their MHC class I recognition capacities. Therefore, the mode of recognition used by KIR largely differs from the conformational changes that characterize T cell receptor or NKG2D interaction with their respective ligands.
Characterization of a monoclonal antibody directed against the biologically active site of human interleukin 1.
Authors: A Köck, M Danner, B M Stadler, T A Luger
Journal: The Journal of Experimental Medicine (1986)

Human IL-1 was successfully used to produce an anti-IL-1 mAb. Anti-IL-1 (IgG2a) blocked IL-1-mediated thymocyte and fibroblast proliferation, but did not interfere with the biological effects of other lymphokines, such as IL-2 or IL-3. The antibody immunoprecipitated biosynthetically radiolabeled 33, 17, and 4 kD IL-1. An immunoadsorbent column yielded 20% of initial activity, and upon HPLC size-exclusion chromatography, affinity-purified IL-1 had a molecular mass of approximately 4 kD. These results provide first evidence of a monoclonal anti-IL-1 that reacts with different species of IL-1 and apparently binds to an epitope close to the active site of IL-1. Thus, anti-IL-1 IgG may be very helpful for further investigations of the molecular as well as biological characteristics of IL-1 and related mediators.
Urinary Concentrating Defect in Hypothyroid Rats
Authors: Melissa A. Cadnapaphornchai, Yang-Wook Kim, Andrey K. Gurevich, Sandra N. Summer, Sandor Falk, Joshua M. Thurman, Robert W. Schrier
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Hypothyroidism is associated with impaired urinary concentrating ability in humans and animals. The purpose of this study was to examine protein expression of renal sodium chloride and urea transporters and aquaporins in hypothyroid rats (HT) with diminished urinary concentration as compared with euthyroid controls (CTL) and hypothyroid rats replaced with L-thyroxine (HT+T). Hypothyroidism was induced by aminotriazole administration. Body weight, water intake, urine output, solute and urea excretion, serum and urine osmolality, serum creatinine, 24-h creatinine clearance, and fractional excretion of sodium were comparable among the three groups. However, with 36 h of water deprivation, HT rats demonstrated significantly greater urine flow rates and decreased urine and medullary osmolality as compared with CTL and HT+T rats at comparable plasma vasopressin concentrations. Western blot analyses revealed decreased renal protein abundance of transporters, including Na-K-2Cl, Na-K-ATPase, and NHE3, in HT rats as compared with CTL and HT+T rats. Protein abundance of renal AQP1 and urea transporters UTA<sub>1</sub> and UTA<sub>2</sub> did not differ significantly among study groups. There was however a significant decrease in protein abundance of AQP2, AQP3, and AQP4 in HT rats as compared with CTL and HT+T rats. These findings demonstrate a decrease in the medullary osmotic gradient secondary to impaired countercurrent multiplication and downregulation of aquaporins 2, 3, and 4 as contributors to the urinary concentrating defect in the hypothyroid rat. E-mail: robert.schrier@uchsc.edu