tbuckley/cabot-search huggingface dataset:
A single N-terminal cysteine in TRPV1 determines activation by pungent compounds from onion and garlic
Authors: Héctor Salazar, Itzel Llorente, Andrés Jara-Oseguera, Refugio García-Villegas, Mika Munari, Sharona E Gordon, León D Islas, Tamara Rosenbaum
Journal: Nature Neuroscience (2008)
Population-wide weight loss and regain in relation to diabetes burden and cardiovascular mortality in Cuba 1980-2010: repeated cross sectional surveys and ecological comparison of secular trends
Authors: M. Franco, U. Bilal, P. Ordunez, M. Benet, A. Morejon, B. Caballero, J. F. Kennelly, R. S. Cooper
Journal: BMJ (2013)

To evaluate the associations between population-wide loss and gain in weight with diabetes prevalence, incidence, and mortality, as well as cardiovascular and cancer mortality trends, in Cuba over a 30 year interval.Repeated cross sectional surveys and ecological comparison of secular trends.Cuba and the province of Cienfuegos, from 1980 to 2010.Measurements in Cienfuegos included a representative sample of 1657, 1351, 1667, and 1492 adults in 1991, 1995, 2001, and 2010, respectively. National surveys included a representative sample of 14 304, 22 851, and 8031 participants in 1995, 2001, and 2010, respectively.Changes in smoking, daily energy intake, physical activity, and body weight were tracked from 1980 to 2010 using national and regional surveys. Data for diabetes prevalence and incidence were obtained from national population based registries. Mortality trends were modelled using national vital statistics.Rapid declines in diabetes and heart disease accompanied an average population-wide loss of 5.5 kg in weight, driven by an economic crisis in the mid-1990s. A rebound in population weight followed in 1995 (33.5% prevalence of overweight and obesity) and exceeded pre-crisis levels by 2010 (52.9% prevalence). The population-wide increase in weight was immediately followed by a 116% increase in diabetes prevalence and 140% increase in diabetes incidence. Six years into the weight rebound phase, diabetes mortality increased by 49% (from 9.3 deaths per 10 000 people in 2002 to 13.9 deaths per 10 000 people in 2010). A deceleration in the rate of decline in mortality from coronary heart disease was also observed.In relation to the Cuban experience in 1980-2010, there is an association at the population level between weight reduction and death from diabetes and cardiovascular disease; the opposite effect on the diabetes and cardiovascular burden was seen on population-wide weight gain.
OC-104 The validity of the royal college of pathologists' stomach cancer minimum dataset in a population using the Northern &amp; Yorkshire cancer registry data: Abstract OC-104 Figure 1
Authors: O Rotimi, H Grabsch, E Morris
Journal: Gut (2012)

<h3>Introduction</h3> Quality histopathological reporting of resceted stomach cancer provides important information for treatment of patients. Sub-standard reporting leads to incorrect staging which impacts on treatment and ultimately survival. Proforma reporting has been introduced as a means of standardisation. This study sought to validate the prognostic significance of the Royal College of Pathologists (RCPath) stomach cancer dataset<sup>1</sup> in a population. <h3>Methods</h3> A retrospective analysis of pathology forms from 1065 resected stomach cancer from 1995 to 2006 was carried out. The variables reported were related to NYCRIS registry survival data using univariate Kaplan–Meier method and Cox proportional regression modelling. <h3>Results</h3> The study population was representative of the Yorkshire stomach cancer population. Survival was poorer with increasing age but it improved significantly from 29.0% (95% CI 23.1% to 35.1%) in 1995–1997 period to 50.5% (95% CI 40.1% to 60.1%) in the 2004–2006 period. Depth of local invasion, nodal stage and completeness of excision are validated as independent prognostic factors in a population setting. Importantly tumour differentiation is shown to be an independent prognostic factor. Patients recorded as well differentiated tumours had significantly better 3-year survival (61.3%; 95% CI 53.2% to 68.4%) compared to moderate (38.4%; 95% CI 33.2% to 43.6%) and poor differentiation (34.1%; 95% CI 30.1% to 38.1%)—Abstract OC-104 figure 1. The effect remains significant after adjusting for age and gender with HR of 1.74 (95% CI 1.11 to 2.71) for moderately differentiated and 2.1 (95% CI 1.3 to 3.4) for poorly differentiated tumours compared to well differentiated tumour. <h3>Conclusion</h3> The variables in the RCPath stomach cancer dataset are validated to be of prognostic significance in a population setting. Importantly, the result showed that there is a significant survival differences between the three grades of differentiation. This is in contrast to the current recommendation by the RCPath that well and moderately differentiated tumours be reported together as a single category.<sup>1</sup> We recommend separating this category in the next version of the RCPath stomach cancer dataset guidelines. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Novelli M</b>. <i>Dataset for the Histopathological Reporting of Gastric Carcinoma. Standards and Datasets for Reporting Cancers</i>. 2nd edn. The Royal College of Pathologists. 2007.
One hump or two? The triggering of calcium release from the sarcoplasmic reticulum and the voltage dependence of contraction in mammalian cardiac muscle
Authors: A. J Levi, P. Brooksby, J. C Hancox
Journal: Cardiovascular Research (1993)

Journal Article One hump or two? The triggering of calcium release from the sarcoplasmic reticulum and the voltage dependence of contraction in mammalian cardiac muscle Get access Allan J Levi, Allan J Levi Department of Physiology, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, United Kingdom: A J Levi, P Brooksby, J C Hancox. Correspondence to Dr Levi. Search for other works by this author on: Oxford Academic PubMed Google Scholar Paul Brooksby, Paul Brooksby Department of Physiology, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, United Kingdom: A J Levi, P Brooksby, J C Hancox. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jules C Hancox Jules C Hancox Department of Physiology, School of Medical Sciences, University Walk, University of Bristol, Bristol BS8 1TD, United Kingdom: A J Levi, P Brooksby, J C Hancox. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 10, October 1993, Pages 1743–1757, https://doi.org/10.1093/cvr/27.10.1743 Published: 01 October 1993 Article history Received: 01 December 1992 Accepted: 01 July 1993 Published: 01 October 1993
Nonmalignant pleural lesions due to environmental exposure to asbestos: a field-based, cross-sectional study
Authors: M. Metintas, S. Metintas, G. Hillerdal, I. Ucgun, S. Erginel, F. Alatas, H. Yildirim
Journal: European Respiratory Journal (2005)

The aim of the present study was to investigate the frequencies of asbestos-related benign pleural diseases in villagers environmentally exposed to asbestos and the factors affecting these frequencies. A field-based, cross-sectional study was designed. In total, 991 villagers from 10 villages, randomly chosen from 67 villages with known use of asbestos-containing white soil in central Anatolia (Turkey), were investigated. The type of asbestos in the white soil was determined for each village, as well as air-borne fibre concentrations. The villagers were investigated with small-size chest roentgenograms and epidemiological features were recorded. The air-borne fibre levels were generally low. Despite this, pleural plaques were found in 14.4% of the villagers, 10.4% had diffuse pleural fibrosis and 0.4% asbestosis. The significant variables for plaques were age, sex, type of asbestos fibre, e.g. actinolite and tremolite, and exposure duration, while there was a negative relationship with cumulative exposure. The variables affecting diffuse pleural fibrosis were age, exposure duration and cumulative exposure. In conclusion, villagers exposed to environmental asbestos have high frequencies of pleural plaques and diffuse pleural fibrosis, similar to occupationally exposed asbestos cohorts. Different types of asbestos appear to result in different frequencies of pleural lesions.
T cell antigen receptor expression in athymic (nu/nu) mice. Evidence for an oligoclonal beta chain repertoire.
Authors: H R MacDonald, R K Lees, C Bron, B Sordat, G Miescher
Journal: The Journal of Experimental Medicine (1987)

The expression of T cell antigen receptors (TCR) in congenitally athymic (nude) mice has been investigated. Lymph node T cells from 4-5-mo-old athymic mice expressed full-length transcripts for the TCR alpha and beta chains at a level two-to three-fold lower than normal littermate (nu/+) controls. Low levels of expression of TCR protein at the surface of a proportion of nude T cells was demonstrated by staining with monoclonal antibodies KJ16-133 and F23.1 (directed against protein products of a family of TCR beta chain variable region genes known as V beta 8). Immunoprecipitation studies confirmed that F23.1 reacted with a similar molecular species on nude and nu/+ T cells. Studies with individual nude mice revealed a striking heterogeneity in the proportion of T cells expressing KJ16/F23.1 that was not seen in normal animals. This heterogeneity correlated with the expression of mRNA specific for V beta 8 but not with total expression of full-length beta chain transcripts. Analysis of Lyt-2+ and L3T4+ T cell subsets in individual nude mice further demonstrated that F23.1 expression was frequently associated with only one subset, and several cases were seen in which all L3T4+ cells expressed F23.1. In contrast, a similar (and constant) proportion of Lyt-2+ or L3T4+ T cells expressed F23.1 in control mice. Southern blotting of Hind III-digested DNA from nude T cells with a C beta probe revealed a more restricted pattern of TCR beta chain rearrangements than was seen for normal T cells. Taken together, these data provide compelling evidence that TCR gene rearrangement and expression can occur extrathymically. Furthermore, they suggest a model according to which the restricted functional repertoire of T cells previously observed in individual nude mice results from an oligoclonal expansion of T cells that have randomly rearranged and expressed TCR beta chain genes.
Chromatin signatures at transcriptional start sites separate two equally populated yet distinct classes of intergenic long noncoding RNAs
Authors: Ana C Marques, Jim Hughes, Bryony Graham, Monika S Kowalczyk, Doug R Higgs, Chris P Ponting
Journal: Genome biology (2013)

Abstract Background Mammalian transcriptomes contain thousands of long noncoding RNAs (lncRNAs). Some lncRNAs originate from intragenic enhancers which, when active, behave as alternative promoters producing transcripts that are processed using the canonical signals of their host gene. We have followed up this observation by analyzing intergenic lncRNAs to determine the extent to which they might also originate from intergenic enhancers. Results We integrated high-resolution maps of transcriptional initiation and transcription to annotate a conservative set of intergenic lncRNAs expressed in mouse erythroblasts. We subclassified intergenic lncRNAs according to chromatin status at transcriptional initiation regions, defined by relative levels of histone H3K4 mono- and trimethylation. These transcripts are almost evenly divided between those arising from enhancer-associated (elncRNA) or promoter-associated (plncRNA) elements. These two classes of 5′ capped and polyadenylated RNA transcripts are indistinguishable with regard to their length, number of exons or transcriptional orientation relative to their closest neighboring gene. Nevertheless, elncRNAs are more tissue-restricted, less highly expressed and less well conserved during evolution. Of considerable interest, we found that expression of elncRNAs, but not plncRNAs, is associated with enhanced expression of neighboring protein-coding genes during erythropoiesis. Conclusions We have determined globally the sites of initiation of intergenic lncRNAs in erythroid cells, allowing us to distinguish two similarly abundant classes of transcripts. Different correlations between the levels of elncRNAs, plncRNAs and expression of neighboring genes suggest that functional lncRNAs from the two classes may play contrasting roles in regulating the transcript abundance of local or distal loci.
Atrial Fibrillation in KCNE1-Null Mice
Authors: Joel Temple, Patricio Frias, Jeffrey Rottman, Tao Yang, Yuejin Wu, E. Etienne Verheijck, Wei Zhang, Chanthaphaychith Siprachanh, Hideaki Kanki, James B. Atkinson, Paul King, Mark E. Anderson, Sabina Kupershmidt, Dan M. Roden
Journal: Circulation Research (2005)

Although atrial fibrillation is the most common serious cardiac arrhythmia, the fundamental molecular pathways remain undefined. Mutations in KCNQ1 , one component of a sympathetically activated cardiac potassium channel complex, cause familial atrial fibrillation, although the mechanisms in vivo are unknown. We show here that mice with deletion of the KCNQ1 protein partner KCNE1 have spontaneous episodes of atrial fibrillation despite normal atrial size and structure. Isoproterenol abolishes these abnormalities, but vagomimetic interventions have no effect. Whereas loss of KCNE1 function prolongs ventricular action potentials in humans, KCNE1 −/− mice displayed unexpectedly shortened atrial action potentials, and multiple potential mechanisms were identified: (1) K + currents (total and those sensitive to the KCNQ1 blocker chromanol 293B) were significantly increased in atrial cells from KCNE1 −/− mice compared with controls, and (2) when CHO cells expressing KCNQ1 and KCNE1 were pulsed very rapidly (at rates comparable to the normal mouse heart and to human atrial fibrillation), the sigmoidicity of I Ks activation prevented current accumulation, whereas cells expressing KCNQ1 alone displayed marked current accumulation at these very rapid rates. Thus, KCNE1 deletion in mice unexpectedly leads to increased outward current in atrial myocytes, shortens atrial action potentials, and enhances susceptibility to atrial fibrillation.
Oral Disposition Index Predicts the Development of Future Diabetes Above and Beyond Fasting and 2-h Glucose Levels
Authors: Kristina M. Utzschneider, Ronald L. Prigeon, Mirjam V. Faulenbach, Jenny Tong, Darcy B. Carr, Edward J. Boyko, Donna L. Leonetti, Marguerite J. McNeely, Wilfred Y. Fujimoto, Steven E. Kahn
Journal: Diabetes Care (2009)

The primary objective of our study was to validate mathematically whether certain measures of insulin sensitivity and insulin release derived from an oral glucose tolerance test (OGTT) are related in a hyperbolic manner and their product thus suitable for use as an estimate of β-cell function (i.e., the oral disposition index). We felt this was an important first step before examining its ability to predict …
Mast cell–expressed orphan receptor CCRL2 binds chemerin and is required for optimal induction of IgE-mediated passive cutaneous anaphylaxis
Authors: Brian A. Zabel, Susumu Nakae, Luis Zúñiga, Ji-Yun Kim, Takao Ohyama, Carsten Alt, Junliang Pan, Hajime Suto, Dulce Soler, Samantha J. Allen, Tracy M. Handel, Chang Ho Song, Stephen J. Galli, Eugene C. Butcher
Journal: The Journal of Experimental Medicine (2008)

Mast cells contribute importantly to both protective and pathological IgE-dependent immune responses. We show that the mast cell–expressed orphan serpentine receptor mCCRL2 is not required for expression of IgE-mediated mast cell–dependent passive cutaneous anaphylaxis but can enhance the tissue swelling and leukocyte infiltrates associated with such reactions in mice. We further identify chemerin as a natural nonsignaling protein ligand for both human and mouse CCRL2. In contrast to other “silent” or professional chemokine interreceptors, chemerin binding does not trigger ligand internalization. Rather, CCRL2 is able to bind the chemoattractant and increase local concentrations of bioactive chemerin, thus providing a link between CCRL2 expression and inflammation via the cell-signaling chemerin receptor CMKLR1.
Relationships between radiographic change, pulmonary function, and bronchoalveolar lavage fluid lymphocytes in farmer's lung disease.
Authors: Y Cormier, J Belanger, A Tardif, P Leblanc, M Laviolette
Journal: Thorax (1986)

Ninety four dairy farmers were investigated by chest radiography, pulmonary function tests, and bronchoalveolar lavage. They were divided into five groups--1: 11 subjects with acute farmer9s lung; 2: 25 subjects with previously diagnosed farmer9s lung who had stayed on their farm; 3: 15 farmers with previously diagnosed farmer9s lung who had left the farm; 4: 23 precipitin positive symptomless farmers; 5: 20 precipitin negative symptomless farmers. The study evaluated the relationships between radiographic changes measured with a scoring system derived from the International Labour Office (ILO) classification, the results of pulmonary function tests, and bronchoalveolar lavage fluid. Thirty eight subjects had radiographic evidence of interstitial pulmonary infiltrates. Group 1 had the highest percentage of lymphocytes recovered by bronchoalveolar lavage (mean 66.3 (SD 19.2]. For all subjects carbon monoxide transfer factor (TLCO) and total lung capacity were negatively correlated with radiographic changes (r = -0.45 and -0.30; p less than 0.001 and less than 0.01 respectively). TLCO was also negatively correlated with radiographic change in group 2 (r = -0.59, p less than 0.005). The percentage of lavage lymphocytes was correlated with radiographic changes for all subjects (r = 0.36, p less than 0.001), but this correlation was not seen within groups. This study shows good correlation between radiographic abnormalities, pulmonary function changes and the cellular composition of bronchoalveolar lavage fluid.
Cardiomyocytes of Noncardiac Origin in Myocardial Biopsies of Human Transplanted Hearts
Authors: Patrick Müller, Peter Pfeiffer, Jörg Koglin, Hans-Joachim Schäfers, Ute Seeland, Ingrid Janzen, Steffi Urbschat, Michael Böhm
Journal: Circulation (2002)

Background — Cell replacement therapy with stem cells able to differentiate into cardiomyocytes has been discussed as a method for remodeling damaged myocardium. A physiological or pathophysiological situation in which this phenomenon might be relevant is not known. We studied the origin of cardiomyocytes in myocardial biopsies of male patients that had undergone sex-mismatched cardiac transplantation to determine whether cells containing a Y chromosome (and therefore being of recipient origin) are able to differentiate into cardiomyocytes. Methods and Results — Myocardial biopsies (n=21) were obtained from the right ventricles of male patients (n=13) who had undergone sex-mismatched heart transplantation. Tissue from 1 nontransplanted male and myocardial biopsies from sex-matched heart–transplanted patients served as controls. Cells from donor and recipient origins were identified by fluorescence in situ hybridization with the use of specific probes for X and Y chromosomes on paraffin sections of the biopsies. Cell types were identified by using immunostaining procedures on the same tissue sections. Cardiomyocytes of recipient origin were detected in 8 of 13 male recipients of female hearts. They were connected by gap junctions with adjacent myocytes. Of the cardiomyocyte nuclei, 0.16±0.04% (mean±SEM, median 0.09%) contained the Y-chromosomal marker. There was no detectable correlation with the extent or number of rejection episodes, time of transplantation, or medical treatment regimen. Conclusions — These results show that regeneration by cells of noncardiac origin (differentiated into cardiomyocytes and physiologically linked to neighboring myocytes) can be detected even in small myocardial biopsies. This may lead to new diagnostic and therapeutic strategies in the treatment of myocardial infarction, inflammatory heart disease, and/or heart failure.
Amplification of Tumor Hypoxic Responses by Macrophage Migration Inhibitory Factor–Dependent Hypoxia-Inducible Factor Stabilization
Authors: Millicent Winner, Albert C. Koong, Beatriz E. Rendon, Wayne Zundel, Robert A. Mitchell
Journal: Cancer Research (2007)

Abstract Low oxygen tension–mediated transcription by hypoxia-inducible factors (HIF) has been reported to facilitate tumor progression, therapeutic resistance, and metastatic adaptation. One previously described target of hypoxia-mediated transcription is the cytokine/growth factor macrophage migration inhibitory factor (MIF). In studies designed to better understand hypoxia-stimulated MIF function, we have discovered that not only is MIF induced by hypoxia in pancreatic adenocarcinoma but MIF is also necessary for maximal hypoxia-induced HIF-1α expression. Cells lacking MIF are defective in hypoxia- and prolyl hydroxylase inhibitor–induced HIF-1α stabilization and subsequent transcription of glycolytic and angiogenic gene products. Moreover, COP9 signalosome subunit 5 (CSN5), a component of the COP9 signalosome previously reported to functionally interact with MIF, has recently been shown to interact with and stabilize HIF-1α. Our results indicate that MIF interacts with CSN5 in pancreatic cancer cells and that MIF-depleted cells display marked defects in hypoxia-induced CSN5/HIF-1α interactions. This functional interdependence between HIF-1α and MIF may represent an important and previously unrecognized protumorigenic axis. [Cancer Res 2007;67(1):186–93]
Survival following adjuvant PCV or temozolomide for anaplastic astrocytoma
Authors: A. A. Brandes
Journal: Neuro-Oncology (2006)

We compared survival in patients with anaplastic astrocytoma (AA) treated with adjuvant procarbazine, lomustine, and vincristine (PCV) with survival in patients treated with temozolomide. A retrospective analysis was made of patients with newly diagnosed AA treated with adjuvant postradiotherapy chemotherapy. Outcome analysis included progression-free survival and overall survival. The following prognostic factors were taken into account: patient age, extent of resection, performance status, presence of contrast enhancement in presurgical imaging, and type of adjuvant treatment. Among 109 AA patients, 49 were treated with PCV and 60 with temozolomide. The treatment groups were well matched for pretreatment characteristics, except for the presence of contrast enhancement. Age, extent of surgery, performance status, and presence of contrast enhancement were statistically significant prognostic factors according to the Cox model analysis of survival. Type of adjuvant chemotherapy was not a significant factor, either for progression-free survival or for overall survival. Hematological toxicity, nonhematological toxicity grades 3-4, and premature discontinuation due to toxicity were observed in 9%, 3% to 5%, and 37%, respectively, of cases in the PCV group versus 4% to 5%, 0, and 0, respectively, in the temozolomide group. Although the present study was not randomized, it was well designed, and it reports on two homogeneous and consecutive series of patients, for whom histology was verified to obtain survival data only for patients with AA following the recent WHO 2000 classification. Even if no survival advantage has been demonstrated for temozolomide versus PCV, we conclude that temozolomide should be preferred because of its greater tolerability.