tbuckley/cabot-search huggingface dataset:
Genioglossal Activation in Patients with Obstructive Sleep Apnea versus Control Subjects
Authors: ROBERT B. FOGEL, ATUL MALHOTRA, GIORA PILLAR, JILL K. EDWARDS, JOSÉE BEAUREGARD, STEVEN A. SHEA, DAVID P. WHITE
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Pharyngeal dilator muscle activation (GGEMG) during wakefulness is greater in patients with obstructive sleep apnea (OSA) than in healthy control subjects, representing a neuromuscular compensatory mechanism for a more collapsible airway. As previous work from our laboratory has demonstrated a close relationship between GGEMG and epiglottic pressure, we examined the relationship between genioglossal activity and epiglottic pressure in patients with apnea and in control subjects across a wide range of epiglottic pressures during basal breathing, negative-pressure (iron-lung) ventilation, heliox breathing, and inspiratory resistive loading. GGEMG was greater in the patients with apnea under all conditions (p < 0.05 for all comparisons), including tonic, phasic, and peak phasic GGEMG. In addition, patients with apnea generated a greater peak epiglottic pressure on a breath-by-breath basis. Although the relationship between GGEMG and epiglottic negative pressure was tight across all conditions in both groups (all R values ⩾ 0.69), there were no significant differences in the slope of this relationship between the two groups (all p values > 0.30) under any condition. Thus, the increased GGEMG seen in the patient with apnea during wakefulness appears to be a product of an increased tonic activation of the muscle, combined with increased negative-pressure generation during inspiration.
Distinguishing Hyperglycemic Changes by Set7 in Vascular Endothelial Cells
Authors: Jun Okabe, Christian Orlowski, Aneta Balcerczyk, Chris Tikellis, Merlin C. Thomas, Mark E. Cooper, Assam El-Osta
Journal: Circulation Research (2012)

Rationale: Epigenetic changes are implicated in the persisting vascular effects of hyperglycemia. The precise mechanism whereby chromatin structure and subsequent gene expression are regulated by glucose in vascular endothelial cells remain to be fully defined. Objective: We have studied the molecular and functional mechanism whereby the Set7 methyltransferase associates with chromatin formation and histone methylation in vascular cells in response to current and previous exposure to glucose. Methods and Results: To characterize the molecular and functional identity of the Set7 protein, we used vascular cells overexpressing or lacking Set7. Chromatin fractionation for mono-methylation of lysine 4 on histone H3 identified methyltransferase activity. Immunofluorescence experiments strongly suggest that Set7 protein accumulates in the nucleus in response to hyperglycemia. Moreover, activation of proinflammatory genes by high glucose is dependent on Set7 but distinguished by H3K4m1 gene patterns. We show that transient hyperglycemia regulates the expression of proinflammatory genes in vascular endothelial cells in vitro and the persistent increase in glucose-induced gene expression in the aorta of nondiabetic mice. Conclusions: This study uncovers that the response to hyperglycemia in vascular endothelial cells involves the H3K4 methyltransferase, Set7. This enzyme appears to regulate glucose-induced chromatin changes and gene expression not only by H3K4m1-dependent but also H3K4m1-independent pathways. Furthermore, Set7 appears to be responsible for sustained vascular gene expression in response to prior hyperglycemia and is a potential molecular mechanism for the phenomenon of hyperglycemic memory.
1159 SERUM ZINC BUT NOT SERUM VITAMIN D LEVELS ARE ASSOCIATED WITH DISEASE SEVERITY AND TREATMENT RESPONSE IN CHRONIC HEPATITIS C VIRUS INFECTION
Authors: S. Kastens, K. Grüngreiff, C. Terkamp, S. Lunemann, J. Jaroszewicz, M. Cornberg, M.P. Manns, H. Wedemeyer
Journal: Journal of Hepatology (2011)
TCT-514 Intracoronary Infusion Of Mononuclear Cells Compared With Standard Therapy After Acute Myocardial Infarction: 2 Year Magnetic Resonance Imaging Results Of The Randomized Controlled Hebe Trial
Authors: Ronak Delewi, Anja van der Laan, Lourens Robbers, Alexander Hirsch, Robin Nijveldt, Pieter van der Vleuten, Jan Tijssen, René Tio, Johannes Waltenberger, Jurrien Ten Berg, Pieter Doevendans, Wim Aengevaeren, Albert van Rossum, Jan Piek, Felix Zijlstra
Journal: Journal of the American College of Cardiology (2012)
Primary pulmonary botryomycosis: a late complication of foreign body aspiration
Authors: J M Tuggey
Journal: Thorax (2000)

Primary pulmonary botryomycosis is a rare cause of haemoptysis and can enter the differential diagnosis of a mass on the plain chest radiograph. The case history is presented of a 63 year old man with botryomycosis which was initially thought to be a bronchial carcinoma. When the diagnosis was made several years later it was found to be secondary to persisting vegetable material in the bronchial tree following previous aspiration.
Parthenolide Inhibits Cancer Stem-Like Side Population of Nasopharyngeal Carcinoma Cells via Suppression of the NF-κB/COX-2 Pathway
Authors: Kun Liao, Bin Xia, Qun-Ying Zhuang, Meng-Jun Hou, Yu-Jing Zhang, Bing Luo, Yang Qiu, Yan-Fang Gao, Xiao-Jie Li, Hui-Feng Chen, Wen-Hua Ling, Cheng-Yong He, Yi-Jun Huang, Yu-Chun Lin, Zhong-Ning Lin
Journal: Theranostics (2015)

Cancer stem cells play a central role in the pathogenesis of nasopharyngeal carcinoma and contribute to both disease initiation and relapse.In this study, cyclooxygenase-2 (COX-2) was found to regulate cancer stem-like side population cells of nasopharyngeal carcinoma cells and enhance cancer stem-like cells' characteristics such as higher colony formation efficiency and overexpression of stemness-associated genes.The regulatory effect of COX-2 on cancer stem-like characteristics may be mediated by ABCG2.COX-2 overexpression by a gain-of-function experiment increased the proportion of side population cells and their cancer stemness properties.The present study also demonstrated that in contrast to the classical chemotherapy drug 5-fluorouracil, which increased the proportion of side population cells and upregulated the expression of COX-2, parthenolide, a naturally occurring small molecule, preferentially targeted the side population cells of nasopharyngeal carcinoma cells and downregulated COX-2.Moreover, we found that the cancer stem-like cells' phenotype was suppressed by using COX-2 inhibitors NS-398 and CAY10404 or knocking down COX-2 with siRNA and shRNA.These findings suggest that COX-2 inhibition is the mechanism by which parthenolide induces cell death in the cancer stem-like cells of nasopharyngeal carcinoma.In addition, parthenolide exhibited an inhibitory effect on nuclear factor-kappa B (NF-κB) nucler translocation by suppressing both the phosphorylation of IκB kinase complex and IκBα degradation.Taken together, these results suggest that parthenolide may exert its cancer stem cell-targeted chemotherapy through the NF-κB/COX-2 pathway.
Prevention of Both Direct and Cross-Priming of Antitumor CD8+ T-Cell Responses following Overproduction of Prostaglandin E2 by Tumor Cells<i>In vivo</i>
Authors: Maryam Ahmadi, David C. Emery, David J. Morgan
Journal: Cancer Research (2008)

Abstract Defects in antitumor immune responses have been associated with increased release of prostaglandin E2 (PGE2) as a result of overexpression of cyclooxygenase (COX)-2 by tumors. In this report, we examine the effects of PGE2 on antitumor CD8+ T-cell responses generated both by cross-presenting dendritic cells and by direct priming by tumor cells. Our data show that PGE2 inhibits dendritic cell maturation, resulting in the abortive activation of naive CD8+ T cells, and is dependent on interleukin-10 production by dendritic cells. Interaction of tumor cells with naïve CD8+ T cells in the presence of PGE2 in vitro results in the induction of CD8+ CD28− T cells, which fail to proliferate or exhibit effector function. In vivo, overexpression of COX-2 by tumor cells results in a decrease in number of tumor-infiltrating dendritic cells and confers the ability of tumor cells to metastasize to the tumor draining lymph nodes. [Cancer Res 2008;68(18):7520–9]
Preventing the Onset of Depressive Disorders: A Meta-Analytic Review of Psychological Interventions
Authors: Pim Cuijpers, Annemieke van Straten, Filip Smit, Cathrine Mihalopoulos, Aartjan Beekman
Journal: American Journal of Psychiatry (2008)

Objective: A growing number of studies have tested the efficacy of preventive interventions in reducing the incidence of depressive disorders. Until now, no meta-analysis has integrated the results of these studies. Method: The authors conducted a meta-analysis. After a comprehensive literature search, 19 studies were identified that met inclusion criteria. The studies had to be randomized controlled studies in which the incidence of depressive disorders (based on diagnostic criteria) in an experimental group could be compared with that of a control group. Results: The mean incidence rate ratio was 0.78, indicating a reduction of the incidence of depressive disorders by 22% in experimental compared with control groups. Heterogeneity was low to moderate (I 2 =33%). The number needed to treat to prevent one case of depressive disorder was 22. Moderator analyses revealed no systematic differences between target populations or types of prevention (universal, selective, or indicated). The data included indications that prevention based on interpersonal psychotherapy may be more effective than prevention based on cognitive-behavioral therapy. Conclusions: Prevention of new cases of depressive disorders does seem to be possible. Prevention may become an important way, in addition to treatment, to reduce the enormous public health burden of depression in the coming years.
Early life mammalian biology and later life physical performance: maximising physiological adaptation
Authors: Andres E Carrillo, Yiannis Koutedakis, Andreas D Flouris
Journal: British Journal of Sports Medicine (2011)

The malleability of mammalian biology during early life, which carries considerable weight throughout the course of the lifespan, may contribute to the creation of a human phenotype ideal for prime physical performance. In this article, the authors consider the East African cohort of exceptional athletes that dominate marathon performance. Since entering international marathon competition in 1960, East Africans have competed at the front of the pack and now hold the top 10 men's marathon times. The authors present lines of evidence supporting that exposure to factors such as altitude and early metabolic adjustments that are inherent in East African early life exert a strong influence in later life physical performance and may collide with a genetic advantage to induce biological changes that allow for a more robust biological response to training in later life.
PIM-1–specific mAb suppresses human and mouse tumor growth by decreasing PIM-1 levels, reducing Akt phosphorylation, and activating apoptosis
Authors: Xiu Feng Hu, Jie Li, Scott Vandervalk, Zeping Wang, Nancy S. Magnuson, Pei Xiang Xing
Journal: Journal of Clinical Investigation (2009)

Provirus integration site for Moloney murine leukemia virus (PIM1) is a proto-oncogene that encodes a serine/threonine kinase with multiple cellular functions. Overexpression of PIM-1 plays a critical role in progression of prostatic and hematopoietic malignancies. Here we describe the generation of a mAb specific for GST-PIM-1, which reacted strongly with most human and mouse cancer tissues and cell lines of prostate, breast, and colon origin but only weakly (if at all) with normal tissues. The mAb binds to PIM-1 in the cytosol and nucleus as well as to PIM-1 on the surface of human and murine cancer cells. Treatment of human and mouse prostate cancer cell lines with the PIM-1-specific mAb resulted in disruption of PIM-1/Hsp90 complexes, decreased PIM-1 and Hsp90 levels, reduced Akt phosphorylation at Ser473, reduced phosphorylation of Bad at Ser112 and Ser136, and increased cleavage of caspase-9, an indicator of activation of the mitochondrial cell death pathway. The mAb induced cancer cell apoptosis and synergistically enhanced antitumor activity when used in combination with cisplatin and epirubicin. In tumor models, the PIM-1-specific mAb substantially inhibited growth of the human prostate cancer cell line DU145 in SCID mice and the mouse prostate cancer cell TRAMP-C1 in C57BL/6 mice. These findings are important because they provide what we believe to be the first in vivo evidence that treatment of prostate cancer may be possible by targeting PIM-1 using an Ab-based therapy.
Evolution in an Ancient Detoxification Pathway Is Coupled with a Transition to Herbivory in the Drosophilidae
Authors: Andrew D. Gloss, Daniel G. Vassão, Alexander L. Hailey, Anna C. Nelson Dittrich, Katharina Schramm, Michael Reichelt, Timothy J. Rast, Andrzej Weichsel, Matthew G. Cravens, Jonathan Gershenzon, William R. Montfort, Noah K. Whiteman
Journal: Molecular Biology and Evolution (2014)

Chemically defended plant tissues present formidable barriers to herbivores. Although mechanisms to resist plant defenses have been identified in ancient herbivorous lineages, adaptations to overcome plant defenses during transitions to herbivory remain relatively unexplored. The fly genus Scaptomyza is nested within the genus Drosophila and includes species that feed on the living tissue of mustard plants (Brassicaceae), yet this lineage is derived from microbe-feeding ancestors. We found that mustard-feeding Scaptomyza species and microbe-feeding Drosophila melanogaster detoxify mustard oils, the primary chemical defenses in the Brassicaceae, using the widely conserved mercapturic acid pathway. This detoxification strategy differs from other specialist herbivores of mustard plants, which possess derived mechanisms to obviate mustard oil formation. To investigate whether mustard feeding is coupled with evolution in the mercapturic acid pathway, we profiled functional and molecular evolutionary changes in the enzyme glutathione S-transferase D1 (GSTD1), which catalyzes the first step of the mercapturic acid pathway and is induced by mustard defense products in Scaptomyza. GSTD1 acquired elevated activity against mustard oils in one mustard-feeding Scaptomyza species in which GstD1 was duplicated. Structural analysis and mutagenesis revealed that substitutions at conserved residues within and near the substrate-binding cleft account for most of this increase in activity against mustard oils. Functional evolution of GSTD1 was coupled with signatures of episodic positive selection in GstD1 after the evolution of herbivory. Overall, we found that preexisting functions of generalized detoxification systems, and their refinement by natural selection, could play a central role in the evolution of herbivory.
Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells.
Authors: M P Bevilacqua, J S Pober, G R Majeau, R S Cotran, M A Gimbrone
Journal: The Journal of Experimental Medicine (1984)

Human monocyte-derived interleukin 1 (IL-1) was found to be a potent inducer of procoagulant activity in cultured human vascular endothelium. IL-1-induced human umbilical vein endothelial cell procoagulant activity (HEC-PCA) was transiently expressed, manifest in intact cell monolayers, and required protein synthesis. Data obtained with coagulation factor-deficient plasma and a goat anti-human apoprotein III antiserum suggested that most, if not all, of IL-1-induced endothelial cell procoagulant activity is tissue factor-like. IL-1 induction of HEC-PCA may be important in the pathogenesis of intravascular coagulation in a variety of immunological and inflammatory conditions.
Effects of exercise training and neuromuscular electrical stimulation on symptoms, muscle strength, exercise capacity, activities of daily living, and quality of life in COPD
Authors: Filiz Tasdemir, Deniz Inal-Ince, Pinar Ergun, Dicle Kaymaz, Nese Demir, Ebru Demirci, Nurcan Egesel
Journal: European Respiratory Journal (2012)

Purpose:  Chronic obstructive pulmonary disease (COPD) have systemic consequences affecting exercise capacity and quality of life. The purpose of this randomized controlled study was to evaluate effects of neuromuscular electrical stimulation (NMES) on symptoms and function in COPD patients undergoing exercise training.   Materials and methods:  Twenty-seven clinically stable COPD patients (62.8±7.5 years, FEV 1 : 40.0±16.4%) were included. The NMES group (n=13) underwent endurance and quadriceps resistance training plus NMES, 2 days/week for 10 weeks. Control group (n=14) was applied the same exercise regimen plus placebo NMES. Incremental (ISWT), and endurance (ESWT) shuttle walk tests, quadriceps strength (1 repetition maximum), Medical Research Council (MRC) dyspnea scale, Fatigue Severity Scale, London Chest Activities of Daily Living Scale (LCADL), and St George Respiratory Questionnaire (SGRQ) were evaluated before and after the treatment.   Results:  In both groups, quadriceps strength, ISWT and ESWT distance increased, and MRC, LCADL and SGRQ scores decreased significantly after the treatment (p 0.05).   Conclusion:  Increase in exercise capacity was more evident when endurance and quadriceps resistance training was applied without NMES. Inclusion of NMES have no additional effects beyond exercise training on muscle strength, symptoms, activities daily living, and quality of life in stable COPD.
A Survey of Diving Behavior and Accidental Water Ingestion among Dutch Occupational and Sport Divers to Assess the Risk of Infection with Waterborne Pathogenic Microorganisms
Authors: Jack Schijven, Ana Maria de Roda Husman
Journal: Environmental Health Perspectives (2006)

Divers may run a higher risk of infection with waterborne pathogens than bathers because of more frequent and intense contact with water that may not comply with microbiologic water quality standards for bathing water. In this study we aimed to estimate the volume of water swallowed during diving as a key factor for infection risk assessment associated with diving. Using questionnaires, occupational and sport divers in the Netherlands were asked about number of dives, volume of swallowed water, and health complaints (nausea, vomiting, diarrhea, and ear, skin, eye, and respiratory complaints). Occupational divers, on average, swallowed 9.8 mL marine water and 5.7 mL fresh surface water per dive. Sport divers swallowed, on average, 9.0 mL marine water; 13 mL fresh recreational water; 3.2 mL river, canal, or city canal water; and 20 mL water in circulation pools. Divers swallowed less water when wearing a full face mask instead of an ordinary diving mask and even less when wearing a diving helmet. A full face mask or a diving helmet is recommended when diving in fecally contaminated water. From the volumes of swallowed water and concentrations of pathogens in fecally contaminated water, we estimated the infection risks per dive and per year to be as high as a few to up to tens of percents. This may explain why only 20% of the divers reported having none of the inquired health complaints within a period of 1 year. It is highly recommended that divers be informed about fecal contamination of the diving water.
Selective and Specific Inhibition of the Plasmodium falciparum Lysyl-tRNA Synthetase by the Fungal Secondary Metabolite Cladosporin
Authors: Dominic Hoepfner, Case W. McNamara, Chek Shik Lim, Christian Studer, Ralph Riedl, Thomas Aust, Susan L. McCormack, David M. Plouffe, Stephan Meister, Sven Schuierer, Uwe Plikat, Nicole Hartmann, Frank Staedtler, Simona Cotesta, Esther K. Schmitt, Frank Petersen, Frantisek Supek, Richard J. Glynne, John A. Tallarico, Jeffrey A. Porter, Mark C. Fishman, Christophe Bodenreider, Thierry T. Diagana, N. Rao Movva, Elizabeth A. Winzeler
Journal: Cell Host & Microbe (2012)

With renewed calls for malaria eradication, next-generation antimalarials need be active against drug-resistant parasites and efficacious against both liver- and blood-stage infections. We screened a natural product library to identify inhibitors of Plasmodium falciparum blood- and liver-stage proliferation. Cladosporin, a fungal secondary metabolite whose target and mechanism of action are not known for any species, was identified as having potent, nanomolar, antiparasitic activity against both blood and liver stages. Using postgenomic methods, including a yeast deletion strains collection, we show that cladosporin specifically inhibits protein synthesis by directly targeting P. falciparum cytosolic lysyl-tRNA synthetase. Further, cladosporin is >100-fold more potent against parasite lysyl-tRNA synthetase relative to the human enzyme, which is conferred by the identity of two amino acids within the enzyme active site. Our data indicate that lysyl-tRNA synthetase is an attractive, druggable, antimalarial target that can be selectively inhibited.
Mac the knife? Macrophages– the double-edged sword of hepatic fibrosis
Authors: Scott L. Friedman
Journal: Journal of Clinical Investigation (2005)

Progression of hepatic fibrosis requires sustained inflammation leading to activation of stellate cells into a fibrogenic and proliferative cell type, whereas regression is associated with stellate cell apoptosis. The contribution of hepatic macrophages to these events has been largely overlooked. However, a study in this issue of the JCI demonstrates that macrophages play pivotal but divergent roles, favoring ECM accumulation during ongoing injury but enhancing matrix degradation during recovery. These findings underscore the potential importance of hepatic macrophages in regulating both stellate cell biology and ECM degradation during regression of hepatic fibrosis.
Air Versus Oxygen in ST-Segment–Elevation Myocardial Infarction
Authors: Dion Stub, Karen Smith, Stephen Bernard, Ziad Nehme, Michael Stephenson, Janet E. Bray, Peter Cameron, Bill Barger, Andris H. Ellims, Andrew J. Taylor, Ian T. Meredith, David M. Kaye
Journal: Circulation (2015)

Oxygen is commonly administered to patients with ST-elevation-myocardial infarction despite previous studies suggesting a possible increase in myocardial injury as a result of coronary vasoconstriction and heightened oxidative stress.We conducted a multicenter, prospective, randomized, controlled trial comparing oxygen (8 L/min) with no supplemental oxygen in patients with ST-elevation-myocardial infarction diagnosed on paramedic 12-lead ECG. Of 638 patients randomized, 441 patients had confirmed ST-elevation-myocardial infarction and underwent primary end-point analysis. The primary end point was myocardial infarct size as assessed by cardiac enzymes, troponin I, and creatine kinase. Secondary end points included recurrent myocardial infarction, cardiac arrhythmia, and myocardial infarct size assessed by cardiac magnetic resonance imaging at 6 months. Mean peak troponin was similar in the oxygen and no oxygen groups (57.4 versus 48.0 μg/L; ratio, 1.20; 95% confidence interval, 0.92-1.56; P=0.18). There was a significant increase in mean peak creatine kinase in the oxygen group compared with the no oxygen group (1948 versus 1543 U/L; means ratio, 1.27; 95% confidence interval, 1.04-1.52; P=0.01). There was an increase in the rate of recurrent myocardial infarction in the oxygen group compared with the no oxygen group (5.5% versus 0.9%; P=0.006) and an increase in frequency of cardiac arrhythmia (40.4% versus 31.4%; P=0.05). At 6 months, the oxygen group had an increase in myocardial infarct size on cardiac magnetic resonance (n=139; 20.3 versus 13.1 g; P=0.04).Supplemental oxygen therapy in patients with ST-elevation-myocardial infarction but without hypoxia may increase early myocardial injury and was associated with larger myocardial infarct size assessed at 6 months.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01272713.