tbuckley/cabot-search huggingface dataset:
Effect of eIF3a on Response of Lung Cancer Patients to Platinum-Based Chemotherapy by Regulating DNA Repair
Authors: Ji-Ye Yin, Jie Shen, Zi-Zheng Dong, Qiong Huang, Mei-Zuo Zhong, De-Yun Feng, Hong-Hao Zhou, Jian-Ting Zhang, Zhao-Qian Liu
Journal: Clinical Cancer Research (2011)

The purpose of this study is to test the hypothesis that eIF3a may regulate the expression of DNA repair proteins which, in turn, affects response of lung cancer patients to treatments by DNA-damaging anticancer drugs.
Differences in Glucose Tolerance Between Fixed-Dose Antihypertensive Drug Combinations in People With Metabolic Syndrome
Authors: George Bakris, Mark Molitch, Ann Hewkin, Mark Kipnes, Pantelis Sarafidis, Kaffa Fakouhi, Peter Bacher, James Sowers
Journal: Diabetes Care (2006)

We sought to test the hypothesis that a fixed-dose combination of trandolapril/verapamil-SR (T/V) is superior to a fixed-dose combination of losartan/hydrochlorothiazide (L/H) on glucose tolerance in hypertensive patients with impaired glucose tolerance (IGT).A prospective, randomized, open-label, blinded-end points design was used to assess the effects of a T/V versus L/H combination in patients with IGT and hypertension (n = 240) followed for up to 1 year. Doses were titrated to a systolic blood pressure <130 mmHg. Primary outcome was change from baseline in a 2-h glucose on oral glucose tolerance test (OGTT) at study end (mean [+/-SD] at follow-up, 46.9 +/- 13.5 weeks). Secondary outcomes included changes in insulin sensitivity, office and 24-h ambulatory blood pressure, incidence of new-onset diabetes, lipids, and inflammatory markers. Data are expressed as means +/- SE unless otherwise noted.Changes at study end were noted in 2-h OGTT glucose (T/V -0.21 +/- 0.36 vs. L/H +1.44 +/- 0.36 mmol/l; P < 0.001) and insulin level (-30.13 +/- 38.38 vs. +84.86 +/- 38.33 pmol/l, respectively; P = 0.025). Worsening of insulin resistance occurred by week 12 (T/V 0.000 +/- 0.001 vs. L/H -0.005 +/- 0.001; P = 0.016). A higher incidence of new-onset diabetes (T/V 11.0 vs. L/H 26.6%; P = 0.002) and HbA1c >7% (2.6 vs. 9.6%, respectively; P = 0.05) occurred at study end.In patients with IGT, normal kidney function, and hypertension, the fixed-dose combination of T/V reduces the risk of new-onset diabetes compared with an L/H-based therapy.
Non-pathogenic bacteria elicit a differential cytokine response by intestinal epithelial cell/leucocyte co-cultures
Authors: D Haller
Journal: Gut (2000)

Intestinal epithelial cells (IEC) are thought to participate in the mucosal defence against bacteria and in the regulation of mucosal tissue homeostasis. Reactivity of IEC to bacterial signals may depend on interactions with immunocompetent cells. To address the question of whether non-pathogenic bacteria modify the immune response of the intestinal epithelium, we co-cultivated enterocyte-like CaCO-2 cells with human blood leucocytes in separate compartments of transwell cultures.CaCO-2/PBMC co-cultures were stimulated with non-pathogenic bacteria and enteropathogenic Escherichia coli. Expression of tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-8, monocyte chemoattracting protein 1 (MCP-1), and IL-10 was studied by enzyme linked immunosorbent assays (cytokine secretion) and by semiquantitative reverse transcription-polymerase chain reaction.Challenge of CaCO-2 cells with non-pathogenic E coli and Lactobacillus sakei induced expression of IL-8, MCP-1, IL-1beta, and TNF-alpha mRNA in the presence of underlying leucocytes. Leucocyte sensitised CaCO-2 cells produced TNF-alpha and IL-1beta whereas IL-10 was exclusively secreted by human peripheral blood mononuclear cells. CaCO-2 cells alone remained hyporesponsive to the bacterial challenge. Lactobacillus johnsonii, an intestinal isolate, showed reduced potential to induce proinflammatory cytokines but increased transforming growth factor beta mRNA in leucocyte sensitised CaCO-2 cells. TNF-alpha was identified as one of the early mediators involved in cellular cross talk. In the presence of leucocytes, discriminative activation of CaCO-2 cells was observed between enteropathogenic E coli and non-pathogenic bacteria.The differential recognition of non-pathogenic bacteria by CaCO-2 cells required the presence of underlying leucocytes. These results strengthen the hypothesis that bacterial signalling at the mucosal surface is dependent on a network of cellular interactions.
The relationships of high energy phosphates, tissue pH, and regional blood flow to diastolic distensibility in the ischemic dog myocardium.
Authors: S Momomura, J S Ingwall, J A Parker, P Sahagian, J J Ferguson, W Grossman
Journal: Circulation Research (1985)

Myocardial ischemia due to increased oxygen demand (pacing tachycardia plus critical coronary stenoses) alters diastolic distensibility and relaxation more than ischemia of comparable duration due to coronary occlusion. To investigate the relationship between myocardial diastolic function and metabolism, we compared myocardial high energy phosphate content, tissue pH, and regional blood flow for these two types of ischemia in anesthetized open-chest dogs. Myocardial biopsies were done with a high-speed air-turbine biopsy drill, permitting rapid (less than 1-second) freezing of tissue samples from both nonischemic and ischemic areas, while myocardial pH was measured with a hydrogen ion-selective polymer membrane implanted in the subendocardium. After 3 minutes of pacing tachycardia in dogs with critical coronary stenoses (demand-type ischemia, n = 14), regional systolic function (% segment shortening by ultrasonic crystals) was mildly depressed (from 19 +/- 2% control to 13 +/- 2% post-pacing, P less than 0.01), while left ventricular diastolic pressure-segment length relations shifted upward, indicating decreased distensibility of the ischemic myocardial segment. Associated with these changes in function, subendocardial adenosine triphosphate decreased (from 31.3 +/- 1.5 to 27.9 +/- 1.0 nmol/mg protein, P less than 0.01), as did creatine phosphate (53.8 +/- 2.1 to 39.6 +/- 2.5 nmol/mg protein, P less than 0.01), while myocardial pH declined slightly (delta pH = -0.14 +/- 0.02, P less than 0.01). In contrast, at 3 minutes of coronary artery occlusion (primary ischemia, n = 14), regional segment shortening was replaced by systolic bulging (% shortening decreased from 17 +/- 2% to -2 +/- 1% during occlusion, P less than 0.01), while left ventricular pressure-segment length relations were not shifted upward, and there was no decrease in diastolic distensibility of the ischemic segment. With coronary artery occlusion, subendocardial adenosine triphosphate declined slightly (33.2 +/- 0.5 to 29.2 +/- 2.0 nmol/mg, P less than 0.05), while creatine phosphate decreased substantially (51.1 +/- 2.3 to 7.8 +/- 1.4 nmol/mg protein, P less than 0.01). Myocardial pH fell strikingly (delta pH = -0.33 +/- 0.03, P less than 0.01), and the decline was 236% of that seen with demand-type ischemia. Regional myocardial blood flow (microsphere technique) showed a decreased endocardial:epicardial (endo:epi) ratio (1.04 +/- 0.04 control vs. 0.40 +/- 0.05 during pacing, P less than 0.01) and absolute subendocardial flow (1.02 +/- 0.47 to 0.47 +/- 0.05 ml/min per g, P less than 0.01) with demand-type ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)
Visual or computer-based measurements: important for interpretation of athletes’ ECG
Authors: H M Berge, K Steine, T E Andersen, E E Solberg, K Gjesdal
Journal: British Journal of Sports Medicine (2014)

Background ECG is recommended for preparticipation health examination in athletes. Owing to a lack of consensus on how to read and interpret athletes’ ECGs, different criteria for abnormality are used. Aims To compare the prevalence of abnormal ECGs and test the correlation between visual and computer-based measurements. Methods In a preparticipation cardiac screening examination of 595 male professional soccer players aged 18–38 years, ECGs were categorised according to the European Society of Cardiology's (ESC) recommendations and the Seattle criteria, respectively. Visual measurements were conducted with callipers on-screen on the averaged PQRST complex in each lead, calculated by the trimmed mean. Computer-based measurements were derived from the medium beat. Heart rhythm and conduction were scored visually by a cardiologist. Categorical variables were compared by κ statistics (K) and continuous variables by intraclass correlation. Results ECGs of good quality were available from 579 players. According to the ESC's recommendations and Seattle criteria, respectively, ECGs were categorised as abnormal in 171 (29.5%) vs 64 (11.1%) players after visual assessment, and in 293 (50.6%; K=0.395) vs 127 (21.9%; K=0.564) after computer-based measurements. Intraclass correlation was very good for measurements of R and S wave amplitudes and moderate to very good for intervals. K was very good for pathological Q wave amplitudes and moderate for T wave inversions. Conclusions Abnormal ECGs were more than twice as common after computer-based than after visual measurements. Such a difference will markedly influence the number of athletes who need further examinations. Reference values may need adjustments dependent on measurement methods.
Supervision of Exercise Testing by Nonphysicians
Authors: Jonathan Myers, Daniel E. Forman, Gary J. Balady, Barry A. Franklin, Jane Nelson-Worel, Billie-Jean Martin, William G. Herbert, Marco Guazzi, Ross Arena
Journal: Circulation (2014)

exercise test; physical exertion; physician's roleThe standard exercise test is a well-established procedure that has been widely used in cardiovascular medicine for many decades, with staffing issues that have changed over time.The test is frequently considered the "gatekeeper" to more expensive and/or invasive procedures since it is often the first diagnostic evaluation when coronary artery disease (CAD) is suspected.Thus, it is used to help guide decisions regarding diagnosis and/or medical and interventional management.Moreover, the prognostic value of aerobic capacity and other variables obtained during exercise is firmly established in those who are apparently healthy and in virtually all patient populations. 1,2Generally, peak or symptomlimited exercise testing is used to detect signs or symptoms of myocardial ischemia and to discern fundamental information on exercise capacity, exercise hemodynamics, dysrhythmias, oxygenation, neuroautonomic health, symptoms, and other physiological responses.In most instances, peak effort entails at least brief periods of high-intensity † Significant.The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel.Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.
1340 HEPATITIS C VIRUS INFECTION ALTERS LIPID METABOLISM DEPENDING ON THE RS12979860 POLYMORPHISM IN THE IL28B GENE
Authors: J.A. del Campo, Á. Rojas, R. Aparcero, R. Ramirez-Lorca, B. Pardo-Yules, M.E. Sáez, L.M. Real, M. Diago, F.J. Morón, I. Carmona, R.J. Andrade, M. Cuaresma, A. Ruiz, M. Romero Gómez
Journal: Journal of Hepatology (2011)
Upper airway size and collapsibility in snorers: evaluation with digital fluoroscopy
Authors: Y Tsushima, J Antila, E Svedstrom, A Vetrio, E Laurikainen, O Polo, M Kormano
Journal: European Respiratory Journal (1996)

This study addressed the question of whether there are any differences in the size and collapsibility of the upper airway measured by digital fluoroscopy, between snorers and controls whilst they were awake and breathing normally; and whether there are any correlations between these measurements and other clinical data. The dynamic changes of the upper airway size were evaluated using digital fluoroscopy in 33 patients and 16 normal controls. The measurements were compared with findings in an overnight sleep study, including a static-charge-sensitive bed (SCSB) and oximeter recordings. The minimum anteroposterior dimension at the velopharyngeal level was smaller in patients with partial upper airway obstruction than in controls (p&lt;0.005); patients with complete obstruction did not differ from the controls. The velopharyngeal airways were also more collapsible in patients with severe partial obstruction (p&lt;0.01) than in controls. At the oropharyngeal and hypopharyngeal levels, the dimensions and the collapsibilities were similar in patients and controls. The velopharyngeal collapsibility correlated with body mass index (p&lt;0.001), whereas the airway size did not. The velopharyngeal collapsibility was more pronounced in patients with frequent episodes of arterial oxyhaemoglobin desaturation during sleep. Velopharyngeal collapsibility associated with high body mass index was the important determinant of nocturnal breathing disturbances. Digital fluoroscopy displays the dynamic changes of the upper airways throughout the respiratory cycle.
Topical 5-aminolaevulinic acid photodynamic therapy for extensive scalp actinic keratoses.
Authors: T. Markham, P. Collins
Journal: British Journal of Dermatology (2001)

Scalp actinic keratoses (AKs) are common, particularly in elderly bald males. Cryotherapy and 5-fluorouracil are effective for localized AKs but are limited in extensive disease. Topical 5-aminolaevulinic acid photodynamic therapy (5-ALA PDT) is an alternative. We treated four patients with extensive scalp AKs with low light dose, low dose-rate topical 5-ALA PDT using a broad-spectrum visible light source. Three patients cleared and one showed significant improvement. Remission lasted 6 months.
Altered cAMP-Dependent Protein Kinase A in Platelets of Patients With Obsessive-Compulsive Disorder
Authors: J Perez, D Tardito, L Ravizza, G Racagni, S Mori, G Maina
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The purpose of this study was to assess cAMP-dependent protein kinase A in patients with obsessive-compulsive disorder (OCD). METHOD: The levels and the activity of protein kinase A were evaluated in whole platelets obtained from 12 unmedicated patients with OCD and 15 healthy comparison subjects. RESULTS: The immunolabeling of protein kinase A regulatory subunits type I and II were significantly greater but that of the catalytic subunit significantly lower in patients with OCD than in healthy subjects. The cAMP-stimulated activity in patients with OCD was significantly lower than that in healthy subjects. CONCLUSIONS: These data suggest a possible role of protein kinase A in the pathophysiology of OCD.
Overweight, Obesity, and Incident Asthma
Authors: David A. Beuther, E. Rand Sutherland
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Although obesity has been implicated as an asthma risk factor, there is heterogeneity in the published literature regarding its role in asthma incidence, particularly in men.To quantify the relationship between categories of body mass index (BMI) and incident asthma in adults and to evaluate the impact of sex on this relationship.Online bibliographic databases were searched for prospective studies evaluating BMI and incident asthma in adults. Independent observers extracted data regarding annualized asthma incidence from studies meeting predetermined criteria, within defined categories of normal weight (BMI < 25), overweight (BMI, 25-29.9), and obesity (BMI >or= 30). Data were analyzed by inverse-variance-weighted, random-effects meta-analysis. Stratified analysis between BMI categories and within sex was performed.Seven studies (n=333,102 subjects) met inclusion criteria. Compared with normal weight, overweight and obesity (BMI >or= 25) conferred increased odds of incident asthma, with an odds ratio (OR) of 1.51 (95% confidence interval [CI], 1.27-1.80). A dose-response effect of elevated BMI on asthma incidence was observed; the OR for incident asthma for normal-weight versus overweight subjects was 1.38 (95% CI, 1.17-1.62) and was further elevated for normal weight versus obesity (OR, 1.92; 95% CI, 1.43-2.59; p<0.0001 for the trend). A similar increase in the OR of incident asthma due to overweight and obesity was observed in men (OR, 1.46; 95% CI, 1.05-2.02) and women (OR, 1.68; 95% CI, 1.45-1.94; p=0.232 for the comparison).Overweight and obesity are associated with a dose-dependent increase in the odds of incident asthma in men and women, suggesting asthma incidence could be reduced by interventions targeting overweight and obesity.
Raltegravir for the treatment of patients co-infected with HIV and tuberculosis (ANRS 12 180 Reflate TB): a multicentre, phase 2, non-comparative, open-label, randomised trial
Authors: Beatriz Grinsztejn, Nathalie De Castro, Vincent Arnold, Valdiléa G Veloso, Mariza Morgado, José Henrique Pilotto, Carlos Brites, José Valdez Madruga, Nêmora Tregnago Barcellos, Breno Riegel Santos, Carla Vorsatz, Catherine Fagard, Marilia Santini-Oliveira, Olivier Patey, Constance Delaugerre, Geneviève Chêne, Jean-Michel Molina
Journal: The Lancet Infectious Diseases (2014)
The role of kisspeptin in the control of gonadotrophin secretion
Authors: A.K. Roseweir, R.P. Millar
Journal: Human Reproduction Update (2008)

Kisspeptins, and their cognate receptor gpr-54, were first found to regulate the hypothalamic–pituitary–gonadal (HPG) axis in 2003, when two groups demonstrated that mutations in gpr-54 cause idiopathic hypogonadotropic hypogonadism characterized by delayed or absent puberty. This review aims to highlight discoveries in the KiSS-1/gpr-54 system, focusing on their regulation of the HPG axis in male and female reproductive systems of both mammalian and non-mammalian vertebrates. A search of PUBMED and the authors' files was done without limitations by language or species for citations relevant to kisspeptin, reproduction and signal transduction. Kisspeptins and gpr-54 are critical for puberty and the regulation of reproduction. Kisspeptins have been implicated in mediating many of the important signals relayed to the gonadotrophin-releasing hormone (GnRH) neuron such as positive and negative feedback, metabolic input and photoperiod. The ability of kisspeptin neurons to co-ordinate different signals impinging on the HPG axis makes it one of the most important regulators of GnRH and the reproductive axis. Kisspeptins are pivotal regulators of the HPG axis and reproduction, with the ability to integrate signals from both internal and external sources. Knowledge about the signalling mechanisms involved in kisspeptin stimulation of GnRH would help improve the understanding of the importance of this critical pathway in reproduction.
Mesenchymal Stromal Cells Derived From Crohn's Patients Deploy Indoleamine 2,3-dioxygenase-mediated Immune Suppression, Independent of Autophagy
Authors: Raghavan Chinnadurai, Ian B Copland, Spencer Ng, Marco Garcia, Mahadev Prasad, Dalia Arafat, Greg Gibson, Subra Kugathasan, Jacques Galipeau
Journal: Molecular Therapy (2015)

Autologous bone marrow-derived mesenchymal stromal cells (MSCs) for adoptive cell therapy of luminal Crohn's disease (CD) are being tested in clinical trials. However, CD is associated with dysregulation of autophagy and its effect on MSC's immunobiology is unknown. Here, we demonstrate no quantitative difference in phenotype, in vitro growth kinetics and molecular signatures to IFNγ between MSCs derived from CD and healthy individuals. CD MSCs were indistinguishable from those derived from healthy controls at inhibiting T-cell proliferation through an indoleamine 2,3-dioxygenase (IDO)-dependent mechanism. Upon IFNγ prelicensing, both MSC populations inhibit T-cell effector functions. Neither a single-nucleotide polymorphism (SNP) rs7820268 in the IDO gene, nor a widely reported CD predisposing SNP ATG16L1rs2241880 modulated the suppressive function of MSCs carrying these haplotypes. IFNγ stimulation or coculture with activated T cells upregulated the expression of autophagy genes and/or vacuoles on MSCs. Pharmacological blockade of autophagy pathway did not reverse the immunosuppressive properties and IFNγ responsiveness of MSCs confirming the absence of a functional link between these two cell biochemical properties. We conclude that autophagy, but not IDO and IFNγ responsiveness, is dispensable for MSC's immunosuppressive properties. MSCs from CD subjects are functionally analogous to those of healthy individuals.
The specificity and cellular origin of phenylethanolamine N-methyltransferase (PNMT)-like immunoreactivity in psoriatic skin
Authors: O. JOHANSSON, A. OLSSON, A. ENHAMRE, J. FRANSSON, H. HAMMAR, S-W. HAN, M. GOLDSTEIN
Journal: British Journal of Dermatology (1990)

Phenylethanolamine N-methyltransferase (PNMT)-like immunoreactivity has been found in psoriatic skin and in this study, PNMT-like immunoreactivity was investigated in the involved and uninvolved skin of six patients with lichen planus and four patients with lichen simplex. No PNMT immunoreactivity was observed in these diseases. Studies were carried out using cultured fibroblasts from two patients with psoriasis from uninvolved and involved areas of skin and from two controls using antibodies to PNMT, as well as antibodies to the chemical messengers somatostatin, substance P, parathyroid hormone and peptide histidine isoleucine amide. No immunoreactivity to these substances was found, and fibroblasts are unlikely to be the cellular origin of the PNMT-like immunoreactivity as seen in psoriatic skin.
Medical Students’ Exposure to Urology in European Schools: The European Association of Urology Proposals for a Convergence Programme
Authors: Remigio Vela Navarrete, Alain Le Duc, Rolf Ackermann, Laurent Boccon-Gibod, Frans Debruyne, Peter Ekman, Udo Jonas, Per-Anders Abrahamsson, Walter Artibani, Chris Chapple, Manfred Wirth
Journal: European Urology (2010)
Inhibition of c-Jun N-Terminal Kinase Limits Lipopolysaccharide-induced Pulmonary Neutrophil Influx
Authors: Patrick G. Arndt, Scott K. Young, Jonathan G. Lieber, Michael B. Fessler, Jerry A. Nick, G. Scott Worthen
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

The influx of neutrophils into the lung is a sentinel event in LPS-induced acute lung inflammation. Previous studies have shown that systemic inhibition of p38 decreases LPS-induced neutrophil influx into the alveolar space but has no effect on pulmonary parenchymal neutrophil accumulation or on microvascular leak, indicating other pathways are important in LPS-induced acute lung inflammation. This study examined the role of c-Jun N-terminal kinase in LPS-induced acute lung inflammation. Systemic inhibition of c-Jun N-terminal kinase, with the specific c-Jun N-terminal kinase inhibitor SP600125, decreased the LPS-induced accumulation of neutrophils into the lung parenchyma and alveolar space. In addition, increases in microvascular leak after LPS exposure were diminished by c-Jun N-terminal kinase inhibition. To determine mechanisms by which systemic c-Jun N-terminal kinase inhibition decreased pulmonary neutrophil influx, LPS and tumor necrosis factor α (TNF-α–)–induced neutrophil actin assembly and retention were examined. Neutrophil actin assembly was decreased after LPS and TNF-α stimulation with SP600125 pretreatment, as well as LPS-induced neutrophil retention. Finally, c-Jun N-terminal kinase inhibition decreased Cdc42 activation after LPS or TNF-α stimulation, thereby providing one mechanism by which c-Jun N-terminal kinase inhibition decreased actin assembly, and thereby pulmonary neutrophil accumulation.