tbuckley/cabot-search huggingface dataset:
A novel antidoping and medical care delivery model at the 2nd Summer Youth Olympic Games (2014), Nanjing China
Authors: Margo Mountjoy, Najla Akef, Richard Budgett, Susan Greinig, Guoping Li, Jegathesan Manikavasagam, Torbjorn Soligard, Xai Haiming, Xiaoye Yang
Journal: British Journal of Sports Medicine (2015)

Antidoping and medical care delivery programmes are required at all large international multisport events.To document and critique the novel antidoping and medical care delivery models implemented at the 2nd Summer Youth Olympic Games, Nanjing 2014.The International Olympic Committee implemented two new models of delivery of antidoping and medical care at the YOG. A review of these models as well as the public health programme and two health educational initiatives in the Cultural and Educational Program was undertaken by the International Olympic Committee.The implementation of the new antidoping model was feasible in the setting of the YOG. The antidoping rules and regulations of the International Olympic Committee were respected. This model enhanced the educational initiative and provided financial as well as human resource savings. The execution of the hospital-based venue model of medical care delivery at the YOG was also feasible in this setting. This model provided a practical infrastructure for the delivery of medical care at multisport events with the goal of providing optimum athlete healthcare. A public health prevention programme was implemented and no public health risks were encountered by the participants or the Nanjing citizens during the YOG. Finally, the implementation of the athlete health educational programmes within the Cultural and Educational Program provided athletes with an opportunity to improve their health and performance.To achieve the goal of protecting athlete health, and of employing effective doping control and education, new alternate models of antidoping and medical care delivery can be implemented.
Measures of nebulizer performance - Comparing like with like
Authors: Ross Hatley, Yulia Degtyareva, Richard Potter
Journal: European Respiratory Journal (2013)

Within nebulizer literature and manufacturers’ information leaflets, many different measures of nebulizer performance are reported: total emitted dose, respirable emitted dose, delivered dose (DD), respirable delivered dose (RDD), mass median aerodynamic diameter (MMAD), mass median diameter, fine particle fraction (FPF), etc. Comparing nebulizer performance can therefore be difficult.

SideStream Reusable (Philips Respironics) and VixOne (Devilbiss) nebulizers were filled with 2.5 mL salbutamol sulphate (Salamol Steri-Neb, 2 mg/mL). DD with an adult breathing pattern (tidal volume=500 mL; breaths per minute=15; inhalation:exhalation ratio=1:1) was determined. Particle size was measured by a Next Generation Impactor at 15 L/min extraction.

View this table:

Table 1: Performance measurements for the nebulizer systems (n=9).





DD was lower from the SideStream Reusable, compared with the VixOne. If high DD is a measure of good performance, then VixOne could be regarded as the better system. However, aerosol quality (MMAD, FPF) is also important; based on these measures the SideStream Reusable was superior. RDD (DD×FPF) is representative of the amount of drug delivered in the respirable range and is probably the closest in vitro measure to in vivo performance. Results for RDD were more favorable from the SideStream Reusable.

Only 4 possible measures of nebulizer performance were considered in this study, but performance results varied. Relative nebulizer comparisons must use the same measure; some measures may be more relevant to in vivo performance.
In-Hospital Mortality in Patients With Acute Decompensated Heart Failure Requiring Intravenous Vasoactive Medications
Authors: William T. Abraham, Kirkwood F. Adams, Gregg C. Fonarow, Maria Rosa Costanzo, Robert L. Berkowitz, Thierry H. LeJemtel, Mei L. Cheng, Janet Wynne
Journal: Journal of the American College of Cardiology (2005)
Differential Effects of Selective Cyclooxygenase-2 Inhibitors on Endothelial Function in Salt-Induced Hypertension
Authors: Matthias Hermann, Giovanni Camici, Aisha Fratton, David Hurlimann, Felix C. Tanner, Jens P. Hellermann, Martin Fiedler, Joachim Thiery, Michel Neidhart, Renate E. Gay, Steffen Gay, Thomas F. Lüscher, Frank Ruschitzka
Journal: Circulation (2003)

Background— In view of the ongoing controversy about potential differences in cardiovascular safety of selective cyclooxygenase (COX)-2 inhibitors (coxibs), we compared the effects of 2 different coxibs and a traditional NSAID on endothelial dysfunction, a well-established surrogate of cardiovascular disease, in salt-induced hypertension. Methods and Results— Salt-sensitive (DS) and salt-resistant (DR) Dahl rats were fed a high-sodium diet (4% NaCl) for 56 days. From days 35 to 56, diclofenac (6 mg · kg −1 · d −1 ; DS-diclofenac), rofecoxib (2 mg · kg −1 · d −1 ; DS-rofecoxib), celecoxib (25 mg · kg −1 · d −1 ; DS-celecoxib) or placebo (DS-placebo) was added to the chow. Blood pressure increased with sodium diet in the DS groups, which was more pronounced after diclofenac and rofecoxib treatment ( P &lt;0.005 versus DS-placebo) but was slightly decreased by celecoxib ( P &lt;0.001 versus DS-placebo). Sodium diet markedly reduced NO-mediated endothelium-dependent relaxations to acetylcholine (10 −10 -10 −5 mol/L) in aortic rings of untreated hypertensive rats ( P &lt;0.005 versus DR-placebo). Relaxation to acetylcholine improved after celecoxib ( P &lt;0.005 versus DS-placebo and DS-rofecoxib) but remained unchanged after rofecoxib and diclofenac treatment. Vasoconstriction after nitric oxide synthase inhibition, indicating basal NO release, with N ω -nitro- l -arginine methyl ester (10 −4 mol/L) was blunted in DS rats ( P &lt;0.05 versus DR-placebo), normalized by celecoxib, but not affected by rofecoxib or diclofenac. Indicators of oxidative stress, 8-isoprostane levels, were elevated in untreated DS rats on 4% NaCl (6.55±0.58 versus 3.65±1.05 ng/mL, P &lt;0.05) and normalized by celecoxib only (4.29±0.58 ng/mL). Conclusions— These data show that celecoxib but not rofecoxib or diclofenac improves endothelial dysfunction and reduces oxidative stress, thus pointing to differential effects of coxibs in salt-induced hypertension.
Transmembrane Proteins in the Tight Junction Barrier
Authors: ALAN S. FANNING, LAURA L. MITIC, JAMES MELVIN ANDERSON
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Three types of transmembrane proteins have been identified within the tight junction, but it remains to be determined how they provide the molecular basis for regulating the paracellular permeability for water, solutes, and immune cells. Several of these proteins localize specifically within the continuous cell-to-cell contacts of the tight junction. One of these, occludin, is a cell adhesion molecule that has been demonstrated to influence ion and solute permeability. The claudins are a family of four-membrane spanning proteins; unexpectedly, other members of this family have already been characterized without recognizing their relationship to tight junctions. Junction adhesion molecule, the most recently identified tight junction component, is a member of the Ig superfamily and influences the paracellular transmigration of immune cells. A plaque of cytoplasmic proteins under the junction may be responsible for scaffolding the transmembrane proteins, creating a link to the perijunctional actin cytoskeleton and transducing regulatory signals that control the paracellular barrier.
Specific Cross-talk between Epidermal Growth Factor Receptor and Integrin αvβ5 Promotes Carcinoma Cell Invasion and Metastasis
Authors: Jill M. Ricono, Miller Huang, Leo A. Barnes, Steven K. Lau, Sara M. Weis, David D. Schlaepfer, Steven K. Hanks, David A. Cheresh
Journal: Cancer Research (2009)

Tyrosine kinase receptors and integrins play essential roles in tumor cell invasion and metastasis. Previously, we showed that epidermal growth factor (EGF) stimulation of pancreatic carcinoma cells led to invasion and metastasis that was blocked by antagonists of integrin alpha(v)beta(5). Here, we show that EGF stimulates metastasis of carcinoma cells via a Src-dependent phosphorylation of p130 CAS leading to activation of Rap1, a small GTPase involved in integrin activation. Specifically, EGF receptor (EGFR)-induced Src activity leads to phosphorylation of a region within the CAS substrate domain, which is essential for Rap1 and alpha(v)beta(5) activation. This pathway induces alpha(v)beta(5)-mediated invasion and metastasis in vivo yet does not influence primary tumor growth or activation of other integrins on these cells. These findings show cross-talk between a tyrosine kinase receptor and an integrin involved in carcinoma cell invasion and metastasis and may explain in part how inhibitors of EGFR affect malignant disease.
Strategies to screen for adrenal suppression in children with asthma: there is no consensus among UK centres
Authors: M Brodlie, M C McKean
Journal: Thorax (2008)

We have read with great interest the recent review by Wilson et al stating the case for an international registry for idiopathic pulmonary fibrosis (IPF).1 This timely proposal prompts us to inform the community that, effective from 1 January 2008, the European Commission is funding a new network entitled “European IPF …
Metformin Use Is Associated with Better Survival of Diabetic Patients with Pancreatic Cancer
Authors: Navid Sadeghi, James L. Abbruzzese, Sai-Ching J. Yeung, Manal Hassan, Donghui Li
Journal: Clinical Cancer Research (2012)

Accumulating evidence suggests that metformin has antitumor activity. The aim of this study was to determine whether metformin use has a survival benefit in patients with pancreatic cancer.We conducted a retrospective study of patients with diabetes and pancreatic cancer treated at The University of Texas MD Anderson Cancer Center (Houston, TX). Information on diabetes history, including treatment modalities and clinical outcome of pancreatic cancer, was collected using personal interviews and medical record review. Survival analysis was carried out using a Kaplan-Meier plot, log-rank test, and Cox proportional hazards regression models.Among the 302 patients identified, there were no significant differences in demographic or major clinical characteristics between the patients who had received metformin (n = 117) and those who had not (n = 185). The 2-year survival rate was 30.1% for the metformin group and 15.4% for the non-metformin group (P = 0.004; χ(2) test). The median overall survival time was 15.2 months for the metformin group, and 11.1 months for the non-metformin group (P = 0.004, log-rank test). Metformin users had a 32% lower risk of death; the HR (95% confidence interval) was 0.68 (0.52-0.89) in a univariate model (P = 0.004), 0.64 (0.48-0.86) after adjusting for other clinical predictors (P = 0.003), and 0.62 (0.44-0.87) after excluding insulin users (P = 0.006). Metformin use was significantly associated with longer survival in patients with nonmetastatic disease only.Our finding that metformin use was associated with improved outcome of patients with diabetes and pancreatic cancer should be confirmed in independent studies. Future research should prospectively evaluate metformin as a supplemental therapy in this population.
Glucosylceramide synthase upregulates MDR1 expression in the regulation of cancer drug resistance through cSrc and β-catenin signaling
Authors: Yong-Yu Liu, Vineet Gupta, Gauri A Patwardhan, Kaustubh Bhinge, Yunfeng Zhao, Jianxiong Bao, Harihara Mehendale, Myles C Cabot, Yu-Teh Li, S Michal Jazwinski
Journal: Molecular Cancer (2010)

Drug resistance is the outcome of multiple-gene interactions in cancer cells under stress of anticancer agents. MDR1 overexpression is most commonly detected in drug-resistant cancers and accompanied with other gene alterations including enhanced glucosylceramide synthase (GCS). MDR1 encodes for P-glycoprotein that extrudes anticancer drugs. Polymorphisms of MDR1 disrupt the effects of P-glycoprotein antagonists and limit the success of drug resistance reversal in clinical trials. GCS converts ceramide to glucosylceramide, reducing the impact of ceramide-induced apoptosis and increasing glycosphingolipid (GSL) synthesis. Understanding the molecular mechanisms underlying MDR1 overexpression and how it interacts with GCS may find effective approaches to reverse drug resistance.MDR1 and GCS were coincidently overexpressed in drug-resistant breast, ovary, cervical and colon cancer cells; silencing GCS using a novel mixed-backbone oligonucleotide (MBO-asGCS) sensitized these four drug-resistant cell lines to doxorubicin. This sensitization was correlated with the decreased MDR1 expression and the increased doxorubicin accumulation. Doxorubicin treatment induced GCS and MDR1 expression in tumors, but MBO-asGCS treatment eliminated "in-vivo" growth of drug-resistant tumor (NCI/ADR-RES). MBO-asGCS suppressed the expression of MDR1 with GCS and sensitized NCI/ADR-RES tumor to doxorubicin. The expression of P-glycoprotein and the function of its drug efflux of tumors were decreased by 4 and 8 times after MBO-asGCS treatment, even though this treatment did not have a significant effect on P-glycoprotein in normal small intestine. GCS transient transfection induced MDR1 overexpression and increased P-glycoprotein efflux in dose-dependent fashion in OVCAR-8 cancer cells. GSL profiling, silencing of globotriaosylceramide synthase and assessment of signaling pathway indicated that GCS transfection significantly increased globo series GSLs (globotriaosylceramide Gb3, globotetraosylceramide Gb4) on GSL-enriched microdomain (GEM), activated cSrc kinase, decreased beta-catenin phosphorylation, and increased nuclear beta-catenin. These consequently increased MDR1 promoter activation and its expression. Conversely, MBO-asGCS treatments decreased globo series GSLs (Gb3, Gb4), cSrc kinase and nuclear beta-catenin, and suppressed MDR-1 expression in dose-dependent pattern.This study demonstrates, for the first time, that GCS upregulates MDR1 expression modulating drug resistance of cancer. GSLs, in particular globo series GSLs mediate gene expression of MDR1 through cSrc and beta-catenin signaling pathway.
Advanced Breast Cancer in Young Women
Authors: J. Peres
Journal: JNCI Journal of the National Cancer Institute (2013)

recent study in the Journal of the American Medical Association disturbed young women.The study, which all the major media picked up, found that the incidence of advanced breast cancer in women younger than 40 years had nearly doubled over three decades.But the importance of the finding, which the authors admit needs confirmation, remains a mystery, and some experts question whether it's real."It could be explained simply by multiple looks at the data," said Peter Ravdin, M.
Pulmonary edema formation with myocardial infarction and left atrial hypertension: intravascular and extravascular pulmonary fluid volumes.
Authors: R A Slutsky, W W Peck, C B Higgins
Journal: Circulation (1983)

The response of pulmonary blood volume (PBV) and extravascular lung water (EVLW) was examined by indicator-dilution techniques in 14 "open chest" dogs, seven that underwent coronary occlusion (group 2) and seven that served as controls (group 1). Data were obtained in a control stage (control stage 1) 45 min after coronary ligation (control stage 2), and 90 min after the left atrial pressure had been increased to approximately 35 mm Hg with a left atrial balloon. In group 2 animals, EVLW increased after coronary ligation without a marked change in left atrial pressure (6.9 +/- 0.4 to 8.2 +/- 0.5 ml/kg mean +/- SD; p less than .05) and increased to 20.1 +/- 1.4 ml/kg after the production of left atrial hypertension (p less than .005 vs control and vs coronary ligation). In the control dogs, EVLW was unchanged 45 min after the initial data had been collected (7.1 +/- 0.7 to 7.0 +/- 0.8 ml/kg). After the production of left atrial hypertension in these dogs, EVLW rose (14.8 +/- 1.2 ml/kg; p less than .005 vs control stage 1 and control stage 2, p less than .01 vs group 2 dogs). PBV did not change significantly with ligation and increased similarly in both groups during left atrial hypertension. We conclude that coronary ligation can increase EVLW, independent of microvascular hydrostatic pressure. During the production of left atrial hypertension there was greater transcapillary fluid flux in group 2 dogs at matched levels of left atrial pressure elevation. This may be due to an alteration in the permeability of the pulmonary capillary membrane during myocardial infarction and provides a partial explanation for the occasional disparity between left heart dynamics and the chest radiograph in acute myocardial infarction.
Identification and transcript analysis of a novel wallaby (Macropus eugenii) basal-like breast cancer cell line
Authors: Julie A Sharp, Sonia L Mailer, Peter C Thomson, Christophe Lefèvre, Kevin R Nicholas
Journal: Molecular Cancer (2008)

A wide variety of animal models have been used to study human breast cancer. Murine, feline and canine mammary tumor cell lines have been studied for several decades and have been shown to have numerous aspects in common with human breast cancer. It is clear that new comparative approaches to study cancer etiology are likely to be productive. A continuous line of breast carcinoma cells (WalBC) was established from a primary breast cancer that spontaneously arose in a female tammar wallaby (Macropus eugenii). The primary tumor was 1.5 cm3 and although large, did not appear to invade the stroma and lacked vimentin expression. The WalBC cell line was cultured from the primary tumor and passaged for 22 months. WalBC cells displayed an epithelial morphology when grown on plastic, were not EGF responsive, stained strongly for cyto-keratin and negatively for vimentin. WalBC cells were shown to be non-invasive within a Matrigel invasion assay and failed to produce tumors following transplantation into nude mice. Gene expression profiling of WalBC cells was performed using a cDNA microarray of nearly 10,000 mammary gland cDNA clones and compared to normal primary mammary cells and profiles of human breast cancer. Seventy-six genes were down-regulated and sixty-six genes were up-regulated in WalBC cells when compared to primary mammary cells. WalBC cells exhibited expression of known markers of basal invasive human breast cancers as well as increased KRT17, KRT 14 and KRT 19, DSP, s100A4, NDRG-1, ANXA1, TK1 and AQP3 gene expression and decreased gene expression of TIMP3, VIM and TAGLN. New targets for breast cancer treatment were identified such as ZONAB, PACSIN3, MRP8 and SUMO1 which have human homologues. This study demonstrates how novel models of breast cancer can provide new fundamental clues regarding cancer etiology which may lead to new human treatments and therapies.
Dilatation reserve of pulmonary arteries at stages of COPD experimental model
Authors: Natalija Kuzubova, Elena Lebedeva, Anatoliy Fedin, Tatiana Preobrazhenskaya
Journal: European Respiratory Journal (2013)

Aim: to evaluate the state of mediator systems in small pulmonary arteries (PAs) stepwise formation of COPD in experiment.  Methods. Model of COPD was induced in rats by nitrogen dioxide (NO 2 ) inhalation for 60 days. At the stages of COPD (15, 30 and 60 days) the effect of reagents-vasodilators (β-adrenoreceptor agonist izopreterenol, IP; NO donor nitrosorbid, NS; acetylcholine, AC; activator of C-fibers capsaicin; corticosteroid beclometasone, B) on isolated PAs (diameter  Results. All reagents dose-dependently decreased vascular tone of intact rat9s PAs. After 15-day NO 2  exposure dilatation effect of low doses of vasodilators do not differ from intact specimens. With increasing doses (0,1 to 10 μg) tension of PAs was reduced by 6.9 vs 22.7 mg in intact rats (p 2  exposure. In the intact group amplitude of PA contraction caused by NS in dose range 1-100 μg decreased by 27.9 mg, and after a 60 days - only 11 mg (p 2  exposure and at a dose of 1000 μg.  Conclusion. In forming a model of COPD functioning of neurotransmitter systems of PA wall was broken that led to a decrease effect of vasodilators on PA vascular tone and could facilitate the development of pulmonary hypertension which is typical of COPD.
Structure-Function Approach Identifies a COOH-Terminal Domain That Mediates Heparanase Signaling
Authors: Liat Fux, Nir Feibish, Victoria Cohen-Kaplan, Svetlana Gingis-Velitski, Sari Feld, Chen Geffen, Israel Vlodavsky, Neta Ilan
Journal: Cancer Research (2009)

Heparanase is an endo-beta-d-glucuronidase capable of cleaving heparan sulfate, activity that is strongly implicated in cellular invasion associated with tumor metastasis, angiogenesis, and inflammation. In addition, heparanase was noted to exert biological functions apparently independent of its enzymatic activity, enhancing the phosphorylation of selected protein kinases and inducing gene transcription. A predicted three-dimensional structure of constitutively active heparanase clearly delineates a TIM-barrel fold previously anticipated for the enzyme. Interestingly, the model also revealed the existence of a COOH-terminal domain (C-domain) that apparently is not an integral part of the TIM-barrel fold. We provide evidence that the C-domain is critical for heparanase enzymatic activity and secretion. Moreover, the C-domain was found to mediate nonenzymatic functions of heparanase, facilitating Akt phosphorylation, cell proliferation, and tumor xenograft progression. These findings support the notion that heparanase exerts enzymatic activity-independent functions, and identify, for the first time, a protein domain responsible for heparanase-mediated signaling. Inhibitors directed against the C-domain, combined with inhibitors of heparanase enzymatic activity, are expected to neutralize heparanase functions and to profoundly affect tumor growth, angiogenesis, and metastasis.