tbuckley/cabot-search huggingface dataset:
Reduced Kidney Function as a Risk Factor for Incident Heart Failure
Authors: Anna Kottgen, Stuart D. Russell, Laura R. Loehr, Ciprian M. Crainiceanu, Wayne D. Rosamond, Patricia P. Chang, Lloyd E. Chambless, Josef Coresh
Journal: Journal of the American Society of Nephrology (2007)

Reduced kidney function is a risk factor for cardiovascular morbidity and mortality, and both heart failure (HF) and kidney failure incidences are increasing. This study therefore sought to determine the effect of decreased kidney function on HF incidence in a population-based study of middle-aged adults. From 1987 through 2002, 14,857 participants of the Atherosclerosis Risk in Communities (ARIC) study who were free of prevalent HF at baseline were followed for incident HF hospitalization or death (International Classification of Diseases, Ninth Revision/10th Revision 428/I50). Estimated GFR (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease (MDRD) Study equation, and kidney function was categorized as normal (eGFR ≥90 ml/min per 1.73 m2; n = 7143), mildly reduced (eGFR 60 to 89 ml/min per 1.73 m2; n = 7311), and moderately/severely reduced (eGFR <60 ml/min per 1.73 m2; n = 403). Cox proportional hazards models were used to control for demographic and cardiovascular risk factors; analyses were stratified by the presence of coronary heart disease at baseline. During a mean follow-up of 13.2 yr, 1193 participants developed HF. The incidence of HF was three-fold higher for individuals with eGFR <60 ml/min per 1.73 m2 compared to the reference group with eGFR ≥90 ml/min per 1.73 m2 (18 versus 6 per 1000 person-years). The overall adjusted relative hazard of developing HF was 1.94 (1.49 to 2.53) for individuals with eGFR <60 ml/min per 1.73 m2 compared to the reference group and was significantly increased for individuals with and without prevalent coronary heart disease at baseline. A substantially greater decline in kidney function occurred in individuals concomitant with HF hospitalization/death compared to those who did not develop HF. In summary, middle-aged adults with moderately/severely reduced kidney function are at high risk for developing HF.
Effects of hypercapnia and inspiratory flow-resistive loading on respiratory activity in chronic airways obstruction.
Authors: M D Altose, W C McCauley, S G Kelsen, N S Cherniack
Journal: Journal of Clinical Investigation (1977)

The respiratory responses to hypercapnia alone and to hypercapnia and flow-resistive loading during inspiration were studied in normal individuals and in eucapnic and hypercapnic patients with chronic airways obstruction. Responses were assessed in terms of minute ventilation and occlusion pressure (mouth pressure during airway occlusion 100 ms after the onset of inspiration). Ventilatory responses to CO2 (deltaV/deltaPCO2) were distinctly subnormal in both groups of patients with airways obstruction. The two groups of patients, however, showed different occlusion pressure responses to CO2 (deltaP100/deltaPCO2): deltaP100/deltaPCO2 was normal in the eucapnic patients but subnormal in the hypercapnic patients. Flow-resistive loading during inspiration reduced deltaV/deltaPCO2 both in normal subjects and in patients with airways obstruction. The occlusion pressure response to CO2 increased in normal subjects during flow-resistive loading but remained unchanged in both groups of patients with chronic airways obstruction. These results indicate that while chemosensitivity as determined by deltaP100/deltaPCO2 is impaired only in hypercapnic patients with chronic airways obstruction, an acute increase in flow resistance elicits a subnormal increase in respiratory efferent activity in both eucapnic and hypercapnic patients.
Critical Function for ADAM9 in Mouse Prostate Cancer
Authors: Lucie Peduto, Victor E. Reuter, David R. Shaffer, Howard I. Scher, Carl P. Blobel
Journal: Cancer Research (2005)

Abstract ADAM9 is a membrane-anchored metalloprotease that is markedly up-regulated in several human carcinomas. Here, we show that ADAM9 is similarly up-regulated in mouse models for prostate, breast, and intestinal carcinoma. To assess whether ADAM9 is critical for the pathogenesis of prostate carcinoma, one of the most common cancers in men, we evaluated how loss of ADAM9 affects tumorigenesis in W10 mice, a mouse model for this disease. In the absence of ADAM9, most tumors in 50-week-old W10 mice were well differentiated, whereas littermate controls expressing wild-type ADAM9 had predominantly poorly differentiated, and in some cases significantly larger, tumors. Moreover, gain-of-function experiments in which ADAM9 was overexpressed in mouse prostate epithelium resulted in significant abnormalities, including epithelial hyperplasia at 4 to 6 months of age, and prostatic intraepithelial neoplasia after 1 year. A potential underlying mechanism for the role of ADAM9 in prostate cancer emerged from cell-based assays: ADAM9 can cleave and release epidermal growth factor and FGFR2iiib from cells, both of which have pivotal functions in the pathogenesis of this disease. Taken together, these results suggest that ADAM9 contributes to the pathogenesis of prostate cancer and potentially also other carcinomas, raising the possibility that ADAM9 might be a good target for antitumor drugs.
Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival
Authors: Ashley Hamilton, G. Vignir Helgason, Mirle Schemionek, Bin Zhang, Svetlana Myssina, Elaine K. Allan, Franck E. Nicolini, Carsten Müller-Tidow, Ravi Bhatia, Valerie G. Brunton, Steffen Koschmieder, Tessa L. Holyoake
Journal: Blood (2011)
<i>CAMTA1</i>, a 1p36 Tumor Suppressor Candidate, Inhibits Growth and Activates Differentiation Programs in Neuroblastoma Cells
Authors: Kai-Oliver Henrich, Tobias Bauer, Johannes Schulte, Volker Ehemann, Hedwig Deubzer, Sina Gogolin, Daniel Muth, Matthias Fischer, Axel Benner, Rainer König, Manfred Schwab, Frank Westermann
Journal: Cancer Research (2011)

A distal portion of human chromosome 1p is often deleted in neuroblastomas and other cancers and it is generally assumed that this region harbors one or more tumor suppressor genes. In neuroblastoma, a 261 kb region at 1p36.3 that encompasses the smallest region of consistent deletion pinpoints the locus for calmodulin binding transcription activator 1 (CAMTA1). Low CAMTA1 expression is an independent predictor of poor outcome in multivariate survival analysis, but its potential functionality in neuroblastoma has not been explored. In this study, we used inducible cell models to analyze the impact of CAMTA1 on neuroblastoma biology. In neuroblastoma cells that expressed little endogenous CAMTA1, its ectopic expression slowed cell proliferation, increasing the relative proportion of cells in G(1)/G(0) phases of the cell cycle, inhibited anchorage-independent colony formation, and suppressed the growth of tumor xenografts. CAMTA1 also induced neurite-like processes and markers of neuronal differentiation in neuroblastoma cells. Further, retinoic acid and other differentiation- inducing stimuli upregulated CAMTA1 expression in neuroblastoma cells. Transciptome analysis revealed 683 genes regulated on CAMTA1 induction and gene ontology analysis identified genes consistent with CAMTA1-induced phenotypes, with a significant enrichment for genes involved in neuronal function and differentiation. Our findings define properties of CAMTA1 in growth suppression and neuronal differentiation that support its assignment as a 1p36 tumor suppressor gene in neuroblastoma.
Complete inhibition of hypothalamic somatostatin activity is only partially responsible for the growth hormone response to strenuous exercise
Authors: Wouter R. de Vries, Salem Ait Abdesselam, Theo J. Schers, Hans C.M. Maas, Mohamoud Osman-Dualeh, Inge Maitimu, Hans P.F. Koppeschaar
Journal: Metabolism (2002)
Glutathione-Related Systems and Modulation of Extracellular Signal–Regulated Kinases Are Involved in the Resistance of AGS Adenocarcinoma Gastric Cells to Diallyl Disulfide–Induced Apoptosis
Authors: Giuseppe Filomeni, Katia Aquilano, Giuseppe Rotilio, Maria R. Ciriolo
Journal: Cancer Research (2005)

Abstract We have previously characterized the cytotoxic action of diallyl disulfide (DADS) on neuroblastoma cells, and we have shown the crucial role of an early and massive reactive oxygen species production in the induction of c-Jun NH2-terminal kinase–mediated apoptotic pathway. In the present work, we report that DADS is ineffective in inducing apoptosis in a human adenocarcinoma gastric cell line (AGS). In particular, we show that AGS cells are able to recover from the p53/p21-mediated cell cycle arrest in the G2-M phase upon DADS treatment without committing cells to death. This event is most likely due to a peculiar surviving pathway of these cells involving: (a) the formation of mixed disulfides between reduced glutathione (GSH) and protein thiols, (b) a higher and inducible glutathione peroxidase activity, and/or (c) an efficient modulation of the phospho-active levels of the extracellular signal–regulated kinases 1 and 2 (ERK 1/2). Moreover, by increasing glutathione peroxidase expression or GSH concentrations, cell cycle arrest is fully abolished; the apoptotic death is induced by either decreasing the availability of intracellular GSH or inhibiting the reactivation of ERK 1/2. Altogether, our data show that ERK 1/2 participates in the active proliferation of AGS cells and that an efficient reactive oxygen species buffering system makes these cells resistant to DADS-mediated detrimental effects. (Cancer Res 2005; 65(24): 11735-42)
Risk Factors for Acute Myocardial Infarction in Latin America
Authors: Fernando Lanas, Alvaro Avezum, Leonelo E. Bautista, Rafael Diaz, Max Luna, Shofiqul Islam, Salim Yusuf
Journal: Circulation (2007)

Current knowledge of the impact of cardiovascular risk factors in Latin America is limited.As part of the INTERHEART study, 1237 cases of first acute myocardial infarction and 1888 age-, sex-, and center-matched controls were enrolled from Argentina, Brazil, Colombia, Chile, Guatemala, and Mexico. History of smoking, hypertension, diabetes mellitus, diet, physical activity, alcohol consumption, psychosocial factors, anthropometry, and blood pressure were recorded. Nonfasting blood samples were analyzed for apolipoproteins A-1 and B-100. Logistic regression was used to estimate multivariate adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Persistent psychosocial stress (OR, 2.81; 95% CI, 2.07 to 3.82), history of hypertension (OR, 2.81; 95% CI, 2.39 to 3.31), diabetes mellitus (OR, 2.59; 95% CI, 2.09 to 3.22), current smoking (OR, 2.31; 95% CI, 1.97 to 2.71), increased waist-to-hip ratio (OR for first versus third tertile, 2.49; 95% CI, 1.97 to 3.14), and increased ratio of apolipoprotein B to A-1 (OR for first versus third tertile, 2.31; 95% CI, 1.83 to 2.94) were associated with higher risk of acute myocardial infarction. Daily consumption of fruits or vegetables (OR, 0.63; 95% CI, 0.51 to 0.78) and regular exercise (OR, 0.67; 95% CI, 0.55 to 0.82) reduced the risk of acute myocardial infarction. Abdominal obesity, abnormal lipids, and smoking were associated with high population-attributable risks of 48.5%, 40.8%, and 38.4%, respectively. Collectively, these risk factors accounted for 88% of the population-attributable risk.Interventions aimed at decreasing behavioral risk factors, lowering blood pressure, and modifying lipids could have a large impact on the risk of acute myocardial infarction among Latin Americans.
The Copenhagen Hip and Groin Outcome Score (HAGOS): development and validation according to the COSMIN checklist
Authors: K Thorborg, P Hölmich, R Christensen, J Petersen, E M Roos
Journal: British Journal of Sports Medicine (2011)

Background Valid, reliable and responsive Patient-Reported Outcome (PRO) questionnaires for young to middle-aged, physically active individuals with hip and groin pain are lacking. Objective To develop and validate a new PRO in accordance with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) recommendations for use in young to middle-aged, physically active patients with long-standing hip and/or groin pain. Methods Preliminary patient interviews (content validity) included 25 patients. Validity, reliability and responsiveness were evaluated in a clinical study including 101 physically active patients (50 women); mean age 36 years, range 18–63 years. Results The Copenhagen Hip and Groin Outcome Score (HAGOS) consists of six separate subscales assessing Pain, Symptoms, Physical function in daily living, Physical function in Sport and Recreation, Participation in Physical Activities and hip and/or groin-related Quality of Life (QOL). Test–retest reliability was substantial, with intraclass correlation coefficients ranging from 0.82 to 0.91 for the six subscales. The smallest detectable change ranged from 17.7 to 33.8 points at the individual level and from 2.7 to 5.2 points at the group level for the different subscales. Construct validity and responsiveness were confirmed with statistically significant correlation coefficients (0.37–0.73, p &lt; 0.01) for convergent construct validity and for responsiveness from 0.56 to 0.69, p &lt; 0.01. Conclusion HAGOS has adequate measurement qualities for the assessment of symptoms, activity limitations, participation restrictions and QOL in physically active, young to middle-aged patients with long-standing hip and/or groin pain and is recommended for use in interventions where the patient's perspective and health-related QOL are of primary interest. Trial registration ClinicalTrials.gov NCT00716729
Efficacy of extracorporeal shock wave treatment in calcaneal enthesophytosis
Authors: R Cosentino
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To evaluate the efficacy of extracorporeal shock wave treatment (ESWT) in calcaneal enthesophytosis. <h3>METHODS</h3> 60 patients (43 women, 17 men) were examined who had talalgia associated with heel spur. A single blind randomised study was performed in which 30 patients underwent a regular treatment (group 1) and 30 a simulated one (shocks of 0 mJ/mm<sup>2</sup> energy were applied) (group 2). Variations in symptoms were evaluated by visual analogue scale (VAS). Variations in the dimension of enthesophytosis were evaluated by<i>x</i> ray examination. Variations in the grade of enthesitis were evaluated by sonography. <h3>RESULTS</h3> A significant decrease of VAS was seen in group 1. Examination by<i>x</i> ray showed morphological modifications (reduction of the larger diameter &gt;1 mm) of the enthesophytosis in nine (30%) patients. Sonography did not show significant changes in the grade of enthesitis just after the end of the treatment, but a significant reduction was seen after one month. In the control group no significant decrease of VAS was seen. No modification was observed by<i>x</i> ray examination or sonography. <h3>CONCLUSION</h3> ESWT is safe and improves the symptoms of most patients with a painful heel, it can also structurally modify enthesophytosis, and reduce inflammatory oedema.
B cell repertoire diversification precedes immunoglobulin receptor expression.
Authors: R L Riley, D E Wylie, N R Klinman
Journal: The Journal of Experimental Medicine (1983)

68 monoclonal antibodies specific for the hemagglutinin (HA) of the influenza virus, PR8, were obtained from sIg- bone marrow B cell precursors stimulated in splenic fragment cultures. Reactivity pattern (RP) analysis demonstrated that these anti-HA antibody responses included at least 29 distinguishable clonotypes. Comparison of the specificities of anti-HA antibodies obtained from sIg- bone marrow cells with those obtained from adult spleen cells indicates that the anti-HA repertoires of the two populations are comparable in diversity. Since the sIg- bone marrow B cell precursor pool presumably has not encountered V region-specific regulatory mechanisms in vivo, our data suggest that substantial diversification of the B cell repertoire precedes surface immunoglobulin (sIg) expression and subsequent interaction with environmental regulatory processes.
Allelic Imbalance in Drosophila Hybrid Heads: Exons, Isoforms, and Evolution
Authors: R. M. Graze, L. L. Novelo, V. Amin, J. M. Fear, G. Casella, S. V. Nuzhdin, L. M. McIntyre
Journal: Molecular Biology and Evolution (2012)

Unraveling how regulatory divergence contributes to species differences and adaptation requires identifying functional variants from among millions of genetic differences. Analysis of allelic imbalance (AI) reveals functional genetic differences in cis regulation and has demonstrated differences in cis regulation within and between species. Regulatory mechanisms are often highly conserved, yet differences between species in gene expression are extensive. What evolutionary forces explain widespread divergence in cis regulation? AI was assessed in Drosophila melanogaster–Drosophila simulans hybrid female heads using RNA-seq technology. Mapping bias was virtually eliminated by using genotype-specific references. Allele representation in DNA sequencing was used as a prior in a novel Bayesian model for the estimation of AI in RNA. Cis regulatory divergence was common in the organs and tissues of the head with 41% of genes analyzed showing significant AI. Using existing population genomic data, the relationship between AI and patterns of sequence evolution was examined. Evidence of positive selection was found in 30% of cis regulatory divergent genes. Genes involved in defense, RNAi/RISC complex genes, and those that are sex regulated are enriched among adaptively evolving cis regulatory divergent genes. For genes in these groups, adaptive evolution may play a role in regulatory divergence between species. However, there is no evidence that adaptive evolution drives most of the cis regulatory divergence that is observed. The majority of genes showed patterns consistent with stabilizing selection and neutral evolutionary processes.
Opposing Mechanisms Support the Voluntary Forgetting of Unwanted Memories
Authors: Roland G. Benoit, Michael C. Anderson
Journal: Neuron (2012)

Reminders of the past can trigger the recollection of events that one would rather forget. Here, using fMRI, we demonstrate two distinct neural mechanisms that foster the intentional forgetting of such unwanted memories. Both mechanisms impair long-term retention by limiting momentary awareness of the memories, yet they operate in opposite ways. One mechanism, direct suppression, disengages episodic retrieval through the systemic inhibition of hippocampal processing that originates from right dorsolateral prefrontal cortex (PFC). The opposite mechanism, thought substitution, instead engages retrieval processes to occupy the limited focus of awareness with a substitute memory. It is mediated by interactions between left caudal and midventrolateral PFC that support the selective retrieval of substitutes in the context of prepotent, unwanted memories. These findings suggest that we are not at the mercy of passive forgetting; rather, our memories can be shaped by two opposite mechanisms of mnemonic control.
Hypoglycemia Caused by Recurrent Renal Cell Carcinoma As Result of Production of High Molecular Weight Insulin-Like Growth Factor 2
Authors: Shingo Kimura, Koji Mitsuzuka, Shigeyuki Yamada, Yasuhiro Kaiho, Mika Watanabe, Yoshihiro Ikeda, Kimio Chiba, Yoichi Arai
Journal: Journal of Clinical Oncology (2014)
High concentrations of pepsin in bronchoalveolar lavage fluid from children with cystic fibrosis are associated with high interleukin-8 concentrations
Authors: P. McNally, E. Ervine, M. D. Shields, B. D. Dimitrov, B. El Nazir, C. C. Taggart, C. M. Greene, N. G. McElvaney, P. Greally
Journal: Thorax (2010)

Gastro-oesophageal reflux is common in children with cystic fibrosis (CF) and is thought to be associated with pulmonary aspiration of gastric contents. The measurement of pepsin in bronchoalveolar lavage (BAL) fluid has recently been suggested to be a reliable indicator of aspiration. The prevalence of pulmonary aspiration in a group of children with CF was assessed and its association with lung inflammation investigated.This was a cross-sectional case-control study. BAL fluid was collected from individuals with CF (n=31) and healthy controls (n=7). Interleukin-8 (IL-8), pepsin, neutrophil numbers and neutrophil elastase activity levels were measured in all samples. Clinical, microbiological and lung function data were collected from medical notes.The pepsin concentration in BAL fluid was higher in the CF group than in controls (mean (SD) 24.4 (27.4) ng/ml vs 4.3 (4.0) ng/ml, p=0.03). Those with CF who had raised pepsin concentrations had higher levels of IL-8 in the BAL fluid than those with a concentration comparable to controls (3.7 (2.7) ng/ml vs 1.4 (0.9) ng/ml, p=0.004). Within the CF group there was a moderate positive correlation between pepsin concentration and IL-8 in BAL fluid (r=0.48, p=0.04). There was no association between BAL fluid pepsin concentrations and age, sex, body mass index z score, forced expiratory volume in 1 s or Pseudomonas aeruginosa colonisation status.Many children with CF have increased levels of pepsin in the BAL fluid compared with normal controls. Increased pepsin levels were associated with higher IL-8 concentrations in BAL fluid. These data suggest that aspiration of gastric contents occurs in a subset of patients with CF and is associated with more pronounced lung inflammation.
Breast-Conserving Surgery With or Without Radiotherapy: Pooled-Analysis for Risks of Ipsilateral Breast Tumor Recurrence and Mortality
Authors: V. Vinh-Hung, C. Verschraegen
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: The objective of the study was to investigate whether radiotherapy or its omission after breast-conserving surgery has measurable consequences on local tumor growth and patient survival. Methods: We conducted a pooled analysis of published randomized clinical trials that compared radiotherapy versus no radiotherapy after breast-conserving surgery. The outcomes studied were ipsilateral breast tumor recurrence and patient death from any cause. The pooled relative risks (RRs) were estimated with a random-effects model. Heterogeneity was assessed using the Cochran Q test. Results: A search of the literature identified 15 trials with a pooled total of 9422 patients available for analysis. The relative risk of ipsilateral breast tumor recurrence after breast-conserving surgery, comparing patients treated with no radiotherapy or radiotherapy, was 3.00 (95% confidence interval [CI] = 2.65 to 3.40). Mortality data were available for 13 trials with a pooled total of 8206 patients. The relative risk of mortality was 1.086 (95% CI = 1.003 to 1.175), corresponding to an estimated 8.6% (95% CI = 0.3% to 17.5%) relative excess mortality if radiotherapy was omitted. Conclusion: Omission of radiotherapy is associated with a large increase in risk of ipsilateral breast tumor recurrence and with a small increase in the risk of patient mortality.
Ultrastructural changes in the rectal mucosa of patients with rheumatoid arthritis.
Authors: G R Struthers, C A Hollywell, C J Morris, K W Walton, P A Bacon
Journal: Annals of the Rheumatic Diseases (1985)

The rectal mucosa from patients with severe rheumatoid arthritis has been examined by electron microscopy. Initially the patients were biopsied for investigation into the diagnosis of amyloidosis or vasculitis, which proved to be negative. A range of ultrastructural abnormalities was found which included proliferation of the rough endoplasmic reticulum, mitochondrial inclusions, association of the mitochondria with cytoplasmic filaments, and marked increase in the number of iron containing siderosomes. Most of these abnormalities have already been reported in rheumatoid synovial tissue, and attention is drawn to the similarity in findings between these two sites.