tbuckley/cabot-search huggingface dataset:
Respiratory muscle specific warm-up and elite swimming performance
Authors: Emma E Wilson, Tricia M McKeever, Claire Lobb, Tom Sherriff, Luke Gupta, Glenn Hearson, Neil Martin, Martin R Lindley, Dominick E Shaw
Journal: British Journal of Sports Medicine (2013)

Background Inspiratory muscle training has been shown to improve performance in elite swimmers, when used as part of routine training, but its use as a respiratory warm-up has yet to be investigated. Aim To determine the influence of inspiratory muscle exercise (IME) as a respiratory muscle warm-up in a randomised controlled cross-over trial. Methods A total of 15 elite swimmers were assigned to four different warm-up protocols and the effects of IME on 100 m freestyle swimming times were assessed.Each swimmer completed four different IME warm-up protocols across four separate study visits: swimming-only warm-up; swimming warm-up plus IME warm-up (2 sets of 30 breaths with a 40% maximum inspiratory mouth pressure load using the Powerbreathe inspiratory muscle trainer); swimming warm-up plus sham IME warm-up (2 sets of 30 breaths with a 15% maximum inspiratory mouth pressure load using the Powerbreathe inspiratory muscle trainer); and IME-only warm-up. Swimmers performed a series of physiological tests and scales of perception (rate of perceived exertion and dyspnoea) at three time points (pre warm-up, post warm-up and post time trial). Results The combined standard swimming warm-up and IME warm-up were the fastest of the four protocols with a 100 m time of 57.05 s. This was significantly faster than the IME-only warm-up (mean difference=1.18 s, 95% CI 0.44 to 1.92, p&lt;0.01) and the swim-only warm-up (mean difference=0.62 s, 95% CI 0.001 to 1.23, p=0.05). Conclusions Using IME combined with a standard swimming warm-up significantly improves 100 m freestyle swimming performance in elite swimmers.
Genetic and Epigenetic Modeling of the Origins of Multidrug-Resistant Cells in a Human Sarcoma Cell Line
Authors: Kevin G. Chen, Yan C. Wang, Marci E. Schaner, Brian Francisco, George E. Durán, Dejan Juric, Lyn M. Huff, Hesed Padilla-Nash, Thomas Ried, Tito Fojo, Branimir I. Sikic
Journal: Cancer Research (2005)

The origin of drug-resistant cells in human cancers has been a fundamental problem of cancer pharmacology. Two major contrasting hypotheses (genetics versus epigenetics) have been proposed to elucidate the mechanisms of acquired drug resistance. In this study, we answer these fundamental questions through investigation of the genetic and epigenetic pathways that control the origin of ABCB1 (MDR1) gene activation with acquired multidrug resistance in drug-sensitive human sarcoma (MES-SA cells). The genetic and epigenetic bases of this selected activation involve the initiation of transcription at a site 112 kb upstream of the ABCB1 proximal promoter (P1) in the drug-resistant cells. This activation was associated with a chromatin-remodeling process characterized by an increase in acetylated histone H3 within a 968-bp region 5' of the ABCB1 upstream promoter. These alterations provide both genetic and epigenetic susceptibility for ABCB1 expression in drug-resistant cells. Complete activation of the ABCB1 gene through the coding region was proposed by interactions of selected trans-alterations or epigenetic changes on the ABCB1 proximal promoter, which occurred during initial drug exposure. Thus, our data provide evidence for a major genomic alteration that changes the chromatin structure of the ABCB1 upstream promoter via acetylation of histone H3 initiating ABCB1 activation, further elucidating the genetic and epigenetic bases that determine chemotherapeutic response in drug-resistant derivatives of MES-SA cells.
Optimal Targeting of HER2–PI3K Signaling in Breast Cancer: Mechanistic Insights and Clinical Implications
Authors: Brent N. Rexer, Carlos L. Arteaga
Journal: Cancer Research (2013)

Abstract The combination of a PI3K inhibitor with trastuzumab has been shown to be effective at overcoming trastuzumab resistance in models of HER2+ breast cancer by inhibiting HER2–PI3K–FOXO–survivin signaling. In this review the potential clinical implications of these findings are discussed. Cancer Res; 73(13); 3817–20. ©2013 AACR.
Molecular Evolution of the Testis TAFs of Drosophila
Authors: V. C. Li, J. C. Davis, K. Lenkov, B. Bolival, M. T. Fuller, D. A. Petrov
Journal: Molecular Biology and Evolution (2009)

The basal transcription machinery is responsible for initiating transcription at core promoters. During metazoan evolution, its components have expanded in number and diversified to increase the complexity of transcriptional regulation in tissues and developmental stages. To explore the evolutionary events and forces underlying this diversification, we analyzed the evolution of the Drosophila testis TAFs (TBP-associated factors), paralogs of TAFs from the basal transcription factor TFIID that are essential for normal transcription during spermatogenesis of a large set of specific genes involved in terminal differentiation of male gametes. There are five testis-specific TAFs in Drosophila, each expressed only in primary spermatocytes and each a paralog of a different generally expressed TFIID subunit. An examination of the presence of paralogs across taxa as well as molecular clock dating indicates that all five testis TAFs likely arose within a span of approximately 38 My 63-250 Ma by independent duplication events from their generally expressed paralogs. Furthermore, the evolution of the testis TAFs has been rapid, with apparent further accelerations in multiple Drosophila lineages. Analysis of between-species divergence and intraspecies polymorphism indicates that the major forces of evolution on these genes have been reduced purifying selection, pervasive positive selection, and coevolution. Other genes that exhibit similar patterns of evolution in the Drosophila lineages are also characterized by enriched expression in the testis, suggesting that the pervasive positive selection acting on the tTAFs is likely to be related to their expression in the testis.
Palmitoyl-L-carnitine modifies the function of vascular endothelium
Authors: N. Inoue, K.-i. Hirata, H. Akita, M. Yokoyama
Journal: Cardiovascular Research (1994)

Journal Article Palmitoyl-L-carnitine modifies the function of vascular endothelium Get access Nobutaka Inoue, Nobutaka Inoue First Department of Internal Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Japan: N Inoue, K Hirata, H Akita, M Yokoyama. Correspondence to Dr Inoue. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ken-ichi Hirata, Ken-ichi Hirata First Department of Internal Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Japan: N Inoue, K Hirata, H Akita, M Yokoyama. Search for other works by this author on: Oxford Academic PubMed Google Scholar Hozuka Akita, Hozuka Akita First Department of Internal Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Japan: N Inoue, K Hirata, H Akita, M Yokoyama. Search for other works by this author on: Oxford Academic PubMed Google Scholar Mitsuhiro Yokoyama Mitsuhiro Yokoyama First Department of Internal Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Japan: N Inoue, K Hirata, H Akita, M Yokoyama. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 1, January 1994, Pages 129–134, https://doi.org/10.1093/cvr/28.1.129 Published: 01 January 1994 Article history Received: 03 February 1993 Accepted: 05 October 1993 Published: 01 January 1994
Identifying Dieters Who Will Develop an Eating Disorder: A Prospective, Population-Based Study
Authors: Christopher G Fairburn, Zafra Cooper, Helen A Doll, Beverley A Davies
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The aims of the study were to identify the characteristics of the dieters most at risk of subsequently developing an eating disorder and to evaluate the feasibility of using a brief questionnaire to identify such dieters in advance. METHOD: A general population cohort of 2,992 young women who were dieting was identified. On four occasions over the subsequent 2 years, this cohort was sent a questionnaire concerning eating habits and attitudes. Participants whose responses suggested that they had developed an eating disorder were interviewed to establish their true case status. The baseline questionnaires of those who did and did not subsequently develop an eating disorder were compared to identify features that predicted future case status. RESULTS: One hundred four of the dieters developed an eating disorder of clinical severity during the 2 years of follow-up. Their baseline questionnaire scores differed in many respects from those who had not developed an eating disorder. Items associated with developing an eating disorder were selected by using three different statistical methods. A simple case-predicting instrument based on one of five items scoring above an optimal cut point had a sensitivity of 71% and a specificity of 72% (overall efficiency of 72%). CONCLUSIONS: Dieters who will develop an eating disorder within the next 2 years have distinctive features. It is feasible to identify them in advance with reasonable efficiency with a brief questionnaire. This questionnaire could be incorporated into routine health assessments, thereby identifying those at high risk.
Mortality trends in women and men with COPD in Ontario, Canada, 1996–2012
Authors: Andrea Gershon, Jeremiah Hwee, J Charles Victor, Andrew Wilton, Robert Wu, Anna Day, Teresa To
Journal: Thorax (2014)

<h3>Importance</h3> COPD is the third leading cause of death worldwide. Mortality trends offer an indication of how well a society is doing in fighting a disease. <h3>Objective</h3> To examine trends in all-cause, lung cancer, cardiovascular and COPD mortalities in people with COPD, overall and in men and women. <h3>Design, setting, participants</h3> Population, cohort study using health administrative data from Ontario, Canada, 1996 to 2011. <h3>Exposure</h3> A previously validated COPD case definition was used to identify all people with COPD. <h3>Main outcomes and measures</h3> All-cause, lung cancer, cardiovascular and COPD mortality rates were determined annually from 1996 to 2011 overall, and in men and women. All-cause trends were compared with all-cause trends in the non-COPD population. All rates were standardised to the 2006 Ontario population. <h3>Results</h3> The prevalence of COPD was 11.0% in 2011. Over the study period, all-cause mortality decreased significantly more in men with COPD than the non-COPD population. The same was not observed in women. COPD-specific and lung cancer mortalities, which started higher in men with COPD, decreased faster in them than in women with COPD with the two rates becoming more similar over time. Cardiovascular disease mortality declined at a relatively equal rate in both sexes. <h3>Conclusions and relevance</h3> Mortality in people with COPD has decreased; however, the decrease has been greater in men than in women. Public health interventions and medical care appear to be improving mortality in individuals with COPD but more research is needed to determine if they are benefiting both sexes equally.
IL-31–IL-31R interactions negatively regulate type 2 inflammation in the lung
Authors: Jacqueline G. Perrigoue, Ji Li, Colby Zaph, Michael Goldschmidt, Phillip Scott, Frederic J. de Sauvage, Edward J. Pearce, Nico Ghilardi, David Artis
Journal: The Journal of Experimental Medicine (2007)

Interleukin (IL) 31Rα (glycoprotein 130–like monocyte receptor and glycoprotein 130–like receptor) heterodimerizes with oncostatin M receptor β to bind IL-31, a cytokine expressed preferentially by CD4+ T helper type 2 (Th2) cells. However, the functions of IL-31–IL-31R signaling in immune regulation remain unknown. Here, we identify a novel role for IL-31R in limiting type 2 inflammation in the lung. After intravenous injection of Schistosoma mansoni eggs, IL-31Rα−/− mice developed severe pulmonary inflammation, characterized by an increase in the area of granulomatous inflammation, increased numbers of resistin-like molecule α+ cells, and enhanced collagen deposition compared to WT counterparts. In vitro, macrophages generated from IL-31Rα−/− mice promoted enhanced ovalbumin-specific CD4+ T cell proliferation and purified naive CD4+ T cells from IL-31Rα−/− mice exhibited enhanced proliferation and expression of Th2 cytokines, identifying a T cell– and macrophage-intrinsic regulatory function for IL-31R signaling. In contrast, the generation of CD4+ T cell–mediated Th1 responses were normal in IL-31Rα−/− mice, suggesting that the regulatory role of IL-31R signaling is limited to type 2 responses. Together, these data implicate IL-31R signaling as a novel negative regulatory pathway that specifically limits type 2 inflammation.
Ventricular Response in Atrial Fibrillation
Authors: M. TEN HOOPEN
Journal: Circulation Research (1966)

The data on durations of the intervals between successive R-R waves in the ECG from patients during atrial fibrillation, reported by Horan and Kistler (Circulation Research 9: 305, 1961) show that the larger the mean and modal value in a record the larger were the shortest and longest durations. The finding that the latter extreme was usually a few times larger than the former has been used in an attempt to organize the data with the help of a probabilistic model. It is assumed that a sequence of intervals is generated, the durations of which are symmetrically distributed, but in fibrillation the process is distorted from time to time and larger intervals occasionally occur. The effects of atrial impulses on conduction through the A-V node are discussed. A mathematical expression describing this phenomenon is derived.
Randomized Phase III Trial of Temsirolimus and Bevacizumab Versus Interferon Alfa and Bevacizumab in Metastatic Renal Cell Carcinoma: INTORACT Trial
Authors: Brian I. Rini, Joaquim Bellmunt, Jill Clancy, Kongming Wang, Andreas G. Niethammer, Subramanian Hariharan, Bernard Escudier
Journal: Journal of Clinical Oncology (2013)

To prospectively determine the efficacy of combination therapy with temsirolimus plus bevacizumab versus interferon alfa (IFN) plus bevacizumab in metastatic renal cell carcinoma (mRCC).In a randomized, open-label, multicenter, phase III study, patients with previously untreated predominantly clear-cell mRCC were randomly assigned, stratified by prior nephrectomy and Memorial Sloan-Kettering Cancer Center prognostic group, to receive the combination of either temsirolimus (25 mg intravenously, weekly) or IFN (9 MIU subcutaneously thrice weekly) with bevacizumab (10 mg/kg intravenously, every 2 weeks). The primary end point was independently assessed progression-free survival (PFS).Median PFS in patients treated with temsirolimus/bevacizumab (n = 400) versus IFN/bevacizumab (n = 391) was 9.1 and 9.3 months, respectively (hazard ratio [HR], 1.1; 95% CI, 0.9 to 1.3; P = .8). There were no significant differences in overall survival (25.8 ν 25.5 months; HR, 1.0; P = .6) or objective response rate (27.0% ν 27.4%) with temsirolimus/bevacizumab versus IFN/bevacizumab, respectively. Patients receiving temsirolimus/bevacizumab reported significantly higher overall mean scores in the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) -15 and FKSI-Disease Related Symptoms subscale compared with IFN/bevacizumab (indicating improvement); however, no differences in global health outcome measures were observed. Treatment-emergent all-causality grade ≥ 3 adverse events more common (P < .001) with temsirolimus/bevacizumab were mucosal inflammation, stomatitis, hypophosphatemia, hyperglycemia, and hypercholesterolemia, whereas neutropenia was more common with IFN/bevacizumab. Incidence of pneumonitis with temsirolimus/bevacizumab was 4.8%, mostly grade 1 or 2.Temsirolimus/bevacizumab combination therapy was not superior to IFN/bevacizumab for first-line treatment in clear-cell mRCC.
A strategy to reduce cardiovascular disease by more than 80%
Authors: N J Wald
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives</b> To determine the combination of drugs and vitamins, and their doses, for use in a single daily pill to achieve a large effect in preventing cardiovascular disease with minimal adverse effects. The strategy was to simultaneously reduce four cardiovascular risk factors (low density lipoprotein cholesterol, blood pressure, serum homocysteine, and platelet function) regardless of pretreatment levels. <b>Design</b> We quantified the efficacy and adverse effects of the proposed formulation from published meta-analyses of randomised trials and cohort studies and a meta-analysis of 15 trials of low dose (50-125 mg/day) aspirin. <b>Outcome measures</b> Proportional reduction in ischaemic heart disease (IHD) events and strokes; life years gained; and prevalence of adverse effects. <b>Results</b> The formulation which met our objectives was: a statin (for example, atorvastatin (daily dose 10 mg) or simvastatin (40 mg)); three blood pressure lowering drugs (for example, a thiazide, a β blocker, and an angiotensin converting enzyme inhibitor), each at half standard dose; folic acid (0.8 mg); and aspirin (75 mg). We estimate that the combination (which we call the Polypill) reduces IHD events by 88% (95% confidence interval 84% to 91%) and stroke by 80% (71% to 87%). One third of people taking this pill from age 55 would benefit, gaining on average about 11 years of life free from an IHD event or stroke. Summing the adverse effects of the components observed in randomised trials shows that the Polypill would cause symptoms in 8-15% of people (depending on the precise formulation). <b>Conclusion</b> The Polypill strategy could largely prevent heart attacks and stroke if taken by everyone aged 55 and older and everyone with existing cardiovascular disease. It would be acceptably safe and with widespread use would have a greater impact on the prevention of disease in the Western world than any other single intervention.
Mouse Mammary Tumor Virus p75 and p110 CUX1 Transgenic Mice Develop Mammary Tumors of Various Histologic Types
Authors: Chantal Cadieux, Valérie Kedinger, Lu Yao, Charles Vadnais, Maria Drossos, Marilène Paquet, Alain Nepveu
Journal: Cancer Research (2009)

The p75 and p110 isoforms of the CUX1 homeodomain protein are overexpressed in breast tumors and cancer cell lines. To assess and compare the ability of these short CUX1 isoforms in driving mammary tumor development, we used site-specific transgenesis into the Hprt locus to generate transgenic mice expressing p75 or p110 CUX1 under the control of the mouse mammary tumor virus-long terminal repeat. We report that mammary tumors developed after a long latency period, and although various histopathologies were observed, the proportion of adenosquamous carcinomas was significantly higher in p75 CUX1 than in p110 CUX1 transgenic mice. Metastasis to the lung was observed in three p75 CUX1 transgenic mice. Comparisons between tumors and adjacent normal mammary glands revealed that transgenes were overexpressed in most but not all tumors, yet in all cases tested, CUX1 DNA binding was increased, suggesting that both higher expression and changes in post-translational modifications can contribute to stimulate transgene activity. Interestingly, higher expression of erbB2 mRNA was seen in most tumors, not only solid carcinomas but also adenosquamous carcinomas, whereas higher expression of various Wnt genes and activation of the beta-catenin pathway was observed primarily in adenosquamous carcinomas. Activation of erbB2 expression appeared to represent a cooperating event that occurred independently of CUX1. In contrast, chromatin immunoprecipitation, short hairpin RNA-mediated knockdown, and reporter assays established that CUX1 is involved in the transcriptional regulation of several Wnt genes. Together, these results support the notion that oncogenic activity of CUX1 can facilitate the establishment of a Wnt/beta-catenin autocrine loop.
ARIA: A Neuromuscular Junction Neuregulin
Authors: Gerald D. Fischbach, Kenneth M. Rosen
Journal: Annual Review of Neuroscience (1997)

▪ Abstract Motor neurons influence the expression and the distribution of acetylcholine receptors in skeletal muscle. Molecules that mediate this carefully choreographed interaction have recently been identified. One of them, ARIA, is a polypeptide purified from chicken brain on the basis of its ability to stimulate the synthesis of muscle acetylcholine receptors. The predicted amino acid sequence suggests that ARIA is synthesized as a transmembrane precursor protein and that it is a member of a family of ligands that activate receptor tyrosine kinases related to the epidermal growth factor receptor. Certain features of the ligand family (the neuregulins) and their receptors (erbBs) are reviewed. Evidence that ARIA plays an important role at developing and mature neuromuscular junctions is discussed.
Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel disease
Authors: R N Cunliffe
Journal: Gut (2001)

<h3>BACKGROUND AND AIMS</h3> Intestinal epithelial cell derived antimicrobial peptides of the defensin family may play a major role in host defence against microorganisms. Our aims were to (i) isolate, characterise, and investigate the processing of human defensin 5 (HD-5) in normal Paneth cells and (ii) investigate expression of HD-5 in active inflammatory bowel disease (IBD). <h3>METHODS</h3> Antiserum raised against chemically synthesised putative mature HD-5 was used for immunohistochemistry and purification of HD-5 from extracts of normal terminal ileal crypts. <h3>RESULTS</h3> In normal and Crohn9s disease terminal ileum, HD-5 immunoreactivity was seen in Paneth cells and in some villous epithelial cells. Normal colonic mucosa did not express HD-5 but HD-5 immunoreactivity was seen in cells in the colonic crypt region of many IBD samples.<i>N</i>-terminal amino acid sequence analysis of HD-5 purified from normal terminal ileal Paneth cells consistently showed the predicted sequence of the precursor form of the peptide. Following stimulation of isolated intact normal terminal ileal crypts, a truncated form of HD-5, with the<i>N</i>-terminal sequence GEDNQLAIS, was detected in the supernatant. <h3>CONCLUSIONS</h3> (i) HD-5 is present only in the precursor form in normal terminal ileal Paneth cells and is processed to the mature form during and/or after secretion, (ii) some villous epithelial cells express HD-5, and (iii) HD-5 is expressed by metaplastic Paneth cells in the colon in IBD.