tbuckley/cabot-search huggingface dataset:
Results of the Predictors of Response to CRT (PROSPECT) Trial
Authors: Eugene S. Chung, Angel R. Leon, Luigi Tavazzi, Jing-Ping Sun, Petros Nihoyannopoulos, John Merlino, William T. Abraham, Stefano Ghio, Christophe Leclercq, Jeroen J. Bax, Cheuk-Man Yu, John Gorcsan, Martin St John Sutton, Johan De Sutter, Jaime Murillo
Journal: Circulation (2008)

Background— Data from single-center studies suggest that echocardiographic parameters of mechanical dyssynchrony may improve patient selection for cardiac resynchronization therapy (CRT). In a prospective, multicenter setting, the Predictors of Response to CRT (PROSPECT) study tested the performance of these parameters to predict CRT response. Methods and Results— Fifty-three centers in Europe, Hong Kong, and the United States enrolled 498 patients with standard CRT indications (New York Heart Association class III or IV heart failure, left ventricular ejection fraction ≤35%, QRS ≥130 ms, stable medical regimen). Twelve echocardiographic parameters of dyssynchrony, based on both conventional and tissue Doppler–based methods, were evaluated after site training in acquisition methods and blinded core laboratory analysis. Indicators of positive CRT response were improved clinical composite score and ≥15% reduction in left ventricular end-systolic volume at 6 months. Clinical composite score was improved in 69% of 426 patients, whereas left ventricular end-systolic volume decreased ≥15% in 56% of 286 patients with paired data. The ability of the 12 echocardiographic parameters to predict clinical composite score response varied widely, with sensitivity ranging from 6% to 74% and specificity ranging from 35% to 91%; for predicting left ventricular end-systolic volume response, sensitivity ranged from 9% to 77% and specificity from 31% to 93%. For all the parameters, the area under the receiver-operating characteristics curve for positive clinical or volume response to CRT was ≤0.62. There was large variability in the analysis of the dyssynchrony parameters. Conclusion— Given the modest sensitivity and specificity in this multicenter setting despite training and central analysis, no single echocardiographic measure of dyssynchrony may be recommended to improve patient selection for CRT beyond current guidelines. Efforts aimed at reducing variability arising from technical and interpretative factors may improve the predictive power of these echocardiographic parameters in a broad clinical setting.
Problem based learning in continuing medical education: a review of controlled evaluation studies
Authors: P B A Smits
Journal: BMJ (2002)

Reviews of undergraduate medical education cautiously support the short term and long term outcomes of problem based learning compared with traditional learning. The effectiveness of problem based learning in continuing medical education, however, has not been reviewed. This review of controlled evaluation studies found limited evidence that problem based learning in continuing medical education increased participants' knowledge and performance and patients' health. There was moderate evidence that doctors are more satisfied with problem based learning.
Enterobacterial Repetitive Intergenic Consensus (ERIC) Sequences in Escherichia coli: Evolution and Implications for ERIC-PCR
Authors: L. A. Wilson
Journal: Molecular Biology and Evolution (2006)

Enterobacterial repetitive intergenic consensus (ERIC) sequences are 127-bp imperfect palindromes that occur in multiple copies in the genomes of enteric bacteria and vibrios. Here we investigate the distribution of these elements in the complete genome sequences of nine Escherichia coli (including Shigella species) strains. There is a significant tendency for copies to be adjacent to more highly expressed genes. There is considerable variation among strains with respect to the presence of an element in any particular intergenic region, but some copies appear to have been conserved since before the divergence of E. coli and Salmonella enterica. In comparisons of orthologous copies between these species, ERIC sequences are surprisingly conserved, implying that they have acquired some function, perhaps related to mRNA stability. The relationships among copies within E. coli are consistent with a master copy mode of generation. Insertion of new copies seems to occur at, and involve duplication of, the dinucleotide TA. Two classes of inserts of about 70 bp each occur at different specific sites within ERIC sequences; these inserts evolve independently of the ERIC sequences. The small number of ERIC sequences in E. coli genomes indicates that a widely used bacterial fingerprinting method using primers based on ERIC sequences (ERIC-PCR) does not rely on the presence of ERIC sequences.
ESTROGENS AND ATHEROSCLEROSIS
Authors: Lauren Nathan and, Gautam Chaudhuri
Journal: The Annual Review of Pharmacology and Toxicology (1997)

▪ Abstract Estrogens prevent heart disease in women and have also been shown to retard atherogenesis in animal models. Estrogens may act at several steps in the atherogenic process to prevent cardiovascular disease. Some of the benefits of estrogens can be ascribed to their ability to favorably alter the lipoprotein profile, i.e. increase high-density lipoprotein and decrease low-density lipoprotein, and also to their ability to prevent oxidative modification of low-density lipoprotein. Other beneficial effects of estrogens include direct actions on the vascular endothelium and vascular smooth muscle, leading to a decrease in the expression of adhesion molecules involved in monocyte adhesion to endothelial cells, and to a decrease in certain chemokines involved in monocyte migration into the subendothelial space. Estrogens may also affect the later stages of atherogenesis. Finally, estrogens may modify the behavior of atherosclerotic vessels by altering their reactivity and thereby promoting vasodilation, and this may also partly account for their ability to prevent clinical events due to cardiovascular disease.
Anti-angiogenic activity of carebastine: a plausible mechanism affecting airway remodelling
Authors: A. De Luisi, G. Mangialardi, R. Ria, G. Acuto, D. Ribatti, A. Vacca
Journal: European Respiratory Journal (2009)

Ebastine is a well-known selective second-generation histamine H 1 receptor antagonist, which is used for seasonal and perennial allergic rhinitis and chronic urticaria. Angiogenesis plays a crucial role in the development of airway inflammation and remodelling in allergic rhinitis and asthmatic patients, in whom, indeed, the mucosa displays increased vascularity and overexpression of vascular endothelial growth factor (VEGF). The aim of the present study was to evaluate the anti-angiogenic properties of carebastine, the active metabolite of ebastine. The effects of carebastine on human umbilical vein endothelial cell (EC) (HUVEC) and human pulmonary artery EC (HPAEC) proliferation, migration and capillary-like tube formation were investigated in vitro , and in the chick embryo chorioallantoic membrane (CAM) assay in vivo . Moreover, the effect of carebastine on phosphorylation of the cell VEGF receptor fetal liver kinase-1, or VEGF receptor 2 (VEGFR-2), and Akt kinase (Akt) was evaluated by Western blotting. Carebastine inhibited VEGF-induced HUVEC and HPAEC proliferation, migration and angiogenesis in a dose-dependent manner in vitro . Cell proliferation was inhibited by 42 and 64% in HUVECs and 62 and 75% in HPAECs upon exposure for 48 and 72 h, respectively, to 20 μM carebastine (p≤0.03), and even more with 30 μM carebastine. Cell migration was inhibited by 37 and 70% in HUVECs (p≤0.03) and 60 and 78% in HPAECs (p≤0.01) in the presence of 10 and 30 μM carebastine, respectively. Carebastine (20 μM) caused a significant reduction (70−86%; p&lt;0.01) in topological parameters of the capillary network produced in vitro by both EC lines on a basement membrane extract. Carebastine (30 and 50 μM) inhibited the VEGF-induced angiogenesis in the CAM assay in vivo two- and three-fold, respectively (p&lt;0.001). Finally, both EC lines, on exposure to 10 and 20 μM carebastine, showed a four- to six-fold reduction (p≤0.01) in both VEGF- and H 1 receptor-induced VEGFR-2 and Akt phosphorylation. Overall, these data provide the first evidence regarding the anti-angiogenic activity of ebastine, and suggest its potential use as an anti-angiogenic molecule, besides its antihistaminic activity for the treatment of allergic diseases in which angiogenesis takes place.
ICAM-1, E-selectin, and TNF alpha expression in labial salivary glands of patients with rheumatoid vasculitis
Authors: R. M. Flipo, T. Cardon, M. C. Copin, M. Vandecandelaere, B. Duquesnoy, A. Janin
Journal: Annals of the Rheumatic Diseases (1997)

To assess the expression of ICAM1, VCAM1, E-selectin, CD44, and TNF alpha in labial salivary glands of patients with rheumatoid vasculitis.Labial salivary glands from six patients with rheumatoid vasculitis before and after treatment, six aged matched rheumatoid arthritis patients without clinical evidence of rheumatoid vasculitis, 10 patients with primary Sjögren syndrome, 10 patients with rheumatoid arthritis and proven secondary Sjögren syndrome, and six controls were tested with specific antibodies.ICAM1, E-selectin, and TNF alpha were significantly expressed in endothelial cells and perivascular cellular infiltrate only in rheumatoid vasculitis before treatment.The expression of ICAM1, E-selectin, and TNF alpha allows an assessment of the activity of the vasculitic process in rheumatoid vasculitis. Labial salivary gland biopsy findings in patients with rheumatoid arthritis and visceral vasculitis without purpura or neuropathy (that is, mesenteric, coronary, or cerebral vasculitis) would be of interest and are examples where labial salivary gland tissue is more accessible than the affected tissue.
Immune-Dependent and Independent Antitumor Activity of GM-CSF Aberrantly Expressed by Mouse and Human Colorectal Tumors
Authors: Rocio G. Urdinguio, Agustin F. Fernandez, Angela Moncada-Pazos, Covadonga Huidobro, Ramon M. Rodriguez, Cecilia Ferrero, Pablo Martinez-Camblor, Alvaro J. Obaya, Teresa Bernal, Adolfo Parra-Blanco, Luis Rodrigo, Maria Santacana, Xavier Matias-Guiu, Beatriz Soldevilla, Gemma Dominguez, Felix Bonilla, Santiago Cal, Carlos Lopez-Otin, Mario F. Fraga
Journal: Cancer Research (2012)

Granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF2) is a cytokine produced in the hematologic compartment that may enhance antitumor immune responses, mainly by activation of dendritic cells. Here, we show that more than one-third of human colorectal tumors exhibit aberrant DNA demethylation of the GM-CSF promoter and overexpress the cytokine. Mouse engraftment experiments with autologous and homologous colon tumors engineered to repress the ectopic secretion of GM-CSF revealed the tumor-secreted GM-CSF to have an immune-associated antitumor effect. Unexpectedly, an immune-independent antitumor effect was observed that depended on the ectopic expression of GM-CSF receptor subunits by tumors. Cancer cells expressing GM-CSF and its receptor did not develop into tumors when autografted into immunocompetent mice. Similarly, 100% of the patients with human colon tumors that overexpressed GM-CSF and its receptor subunits survived at least 5 years after diagnosis. These data suggest that expression of GM-CSF and its receptor subunits by colon tumors may be a useful marker for prognosis as well as for patient stratification in cancer immunotherapy.
Lost in Transgenesis
Authors: Jennifer Davis, Marjorie Maillet, Joseph M. Miano, Jeffery D. Molkentin
Journal: Circulation Research (2012)

The advent of modern mouse genetics has benefited many fields of diseased-based research over the past 20 years, none perhaps more profoundly than cardiac biology. Indeed, the heart is now arguably one of the easiest tissues to genetically manipulate, given the availability of an ever-growing tool chest of molecular reagents/promoters and "facilitator" mouse lines. It is now possible to modify the expression of essentially any gene or partial gene product in the mouse heart at any time, either gain or loss of function. This review is designed as a handbook for the nonmouse geneticist and/or junior investigator to permit the successful manipulation of any gene or RNA product in the heart, while avoiding artifacts. In the present review, guidelines, pitfalls, and limitations are presented so that rigorous and appropriate examination of cardiac genotype-phenotype relationships can be performed. This review uses examples from the field to illustrate the vast spectrum of experimental and design details that must be considered when using genetically modified mouse models to study cardiac biology.
Metabisulphite-induced occupational asthma in a radiographer
Authors: R. Merget
Journal: European Respiratory Journal (2005)

There is epidemiological evidence for an increased prevalence of occupational asthma among radiographers. However, the causes of darkroom disease are not yet defined. A 37-year-old female radiographer reported work-related asthma ∼2 yrs after starting work in a local hospital. She was atopic and showed bronchial hyperresponsiveness to methacholine. Occupational-type exposure with a fixing agent, but not with a developer, produced an immediate-type asthmatic reaction. As the fixing agent contained sodium metabisulphite (SMBS), a substance known to cause asthma, bronchial challenges with SMBS were performed in the patient and nine asthmatic controls. The patient showed a positive bronchial immediate reaction on 2 separate days after inhalation of 48 and 96 µg SMBS, and one control also showed a significant fall in forced expiratory volume in one second after inhalation of 12 µg SMBS. The positive reaction in the control subject argues for a greater susceptibility of both persons to SMBS or its reaction product sulphur dioxide, rather than for a new occupational allergen. It is concluded that sodium metabisulphite exposure should be recognised as a cause of darkroom asthma.
No evidence for bradykinin hydrolysis in human erythrocyte suspensions: H NMR studies
Authors: Serena J. Hyslop, Glenn F. King, Philip W. Kuchel
Journal: American Journal of Hematology (1987)

Abstract In view of their permeability to small peptides, it has been postulated that human erythrocytes may play a role in terminating the action of some circulating peptide hormones. Work using classical paper chromatographic techniques for detecting free amino acids indicated that the octapeptide, des‐(Arg 9 )‐bradykinin, enters these cells and its amino‐terminal arginine residue is released by cytosolic aminopeptidase‐P. We have used 1 H NMR to monitor directly the release of arginine from bradykinin. The hydrolytic reaction rate in hemolysates, with an initial peptide concentration of 13.0 mmol l −1 was 6.5 mmol (1 packed red cell) −1 h −1 . But no reaction was evident after a 4.5‐h incubation with intact cells, thus contradicting the earlier suggestion that erythrocytes are involved in the primary inactivation of this hormone. This is consistent with our previous findings that the pentapeptide leu‐enkephalin fails to enter human erythrocytes but that its lower‐order degradation products may do so.
The Clinical Course of Patients with Idiopathic Pulmonary Fibrosis
Authors: Fernando J. Martinez, Sharon Safrin, Derek Weycker, Karen M. Starko, Williamson Z. Bradford, Talmadge E. King, Kevin R. Flaherty, David A. Schwartz, Paul W. Noble, Ganesh Raghu, Kevin K. Brown
Journal: Annals of Internal Medicine (2005)

Background: Prospective data defining the clinical course in idiopathic pulmonary fibrosis (IPF) are sparse. Objective: To analyze the clinical course of patients with mild to moderate IPF. Design: Analysis of data from the placebo group of a randomized, controlled trial evaluating interferon-γ1b. Setting: Academic and community medical centers. Patients: 168 patients in the placebo group of a trial evaluating interferon-γ1b. Measurements: Measures of physiology and dyspnea assessed at 12-week intervals; hospitalizations; and the pace of deterioration and cause of death over a median period of 76 weeks. Results: Physiologic variables changed minimally during the study. However, 23% of patients required hospitalization for a respiratory disorder and 21% died. Idiopathic pulmonary fibrosis was the primary cause of death in 89% of patients who died, and an apparent acute clinical deterioration preceded death in 47% of these patients. Limitations: The instrument used to define the pace of deterioration and cause of death was applied retrospectively. Conclusions: Recognition of the common occurrence of acute fatal deterioration in patients with mild to moderate IPF has important implications for monitoring patients and supports early referral for lung transplantation. *A complete list of the IPF Study Group is available from reference 3: Raghu G, Brown KK, Bradford WZ, Starko K, Noble PW, Schwartz DA, et al. A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2004;350:125-33.
Terbinafine: tolerability in general medical practice
Authors: None O'sullivan
Journal: British Journal of Dermatology (1999)

Four open, prospective, postmarketing studies with consistent protocols were undertaken, involving over 25,000 patients and nearly 3600 physicians in four European countries (UK, Netherlands, Germany and Austria). The purpose was to determine the tolerability of terbinafine when prescribed to a large, unselected patient population in general medical practice. Patients were recruited from dermatology departments and from general and family practitioners. All received at least one dose of terbinafine. No specific exclusion criteria were applied. The only treatment instructions provided were those contained in the manufacturer's product information. Patients were monitored for adverse events at baseline, during treatment, and at the end of treatment. Of the 25,884 patients entering the study, 38.6% (9991) had concomitant disease, 42.8% (11,078) were taking other medications, and 22.7% (5876) were older than 60 years. The predominant indication for prescribing terbinafine was onychomycosis. Mean duration of treatment was 13.2 weeks. No adverse events were reported in 89.5% (23,167) of patients. The remaining 10.5% (2717) reported one or more adverse events, primarily gastrointestinal (4.9%) or dermatological (2.3%). A total of 115 serious adverse events were recorded, but of these only four were probably and eight possibly related to terbinafine. There were no reported drug-drug interactions, even in patients receiving concomitant medications metabolized by cytochrome P-450 enzymes. There were also no clinically significant drug-disease interactions. In conclusion, terbinafine is well tolerated in an unselected general practice population. This confirms its good tolerability previously established during controlled clinical trials.
817 POSITIVE PREDICTIVE VALUE OF EARLY ANTIVIRAL RESPONSE PROFILE WITH ALBINTERFERON ALFA-2B IN IFN-NAIVE PATIENTS WITH GENOTYPE 1, CHRONIC HEPATITIS C
Authors: A.U. Neumann, S. Zeuzem, E. Yoshida, Y. Benhamou, S. Pianko, J.G. McHutchison, E. Pulkstenis, G.M. Subramanian
Journal: Journal of Hepatology (2008)
Fat, Protein, and Meat Consumption and Renal Cell Cancer Risk: A Pooled Analysis of 13 Prospective Studies
Authors: Jung Eun Lee, Donna Spiegelman, David J. Hunter, Demetrius Albanes, Leslie Bernstein, Piet A. van den Brandt, Julie E. Buring, Eunyoung Cho, Dallas R. English, Jo L. Freudenheim, Graham G. Giles, Saxon Graham, Pamela L. Horn-Ross, Niclas Håkansson, Michael F. Leitzmann, Satu Männistö, Marjorie L. McCullough, Anthony B. Miller, Alexander S. Parker, Thomas E. Rohan, Arthur Schatzkin, Leo J. Schouten, Carol Sweeney, Walter C. Willett, Alicja Wolk, Shumin M. Zhang, Stephanie A. Smith-Warner
Journal: JNCI Journal of the National Cancer Institute (2008)

BackgroundResults of several case–control studies suggest that high consumption of meat (all meat, red meat, or processed meat) is associated with an increased risk of renal cell cancer, but only a few prospective studies have examined the associations of intakes of meat, fat, and protein with renal cell cancer.
Delayed Enhanced Nitric Oxide–Mediated Coronary Vasodilation Following Brief Ischemia and Prolonged Reperfusion in Conscious Dogs
Authors: Song-Jung Kim, Bijan Ghaleh, Raymond K. Kudej, Cheng-Hsiung Huang, Thomas H. Hintze, Stephen F. Vatner
Journal: Circulation Research (1997)

The goal of this study was to determine both the early and delayed effects of a brief (10-minute) coronary artery occlusion (CAO) and prolonged (5-day) reperfusion (CAR) on coronary endothelial function. Fourteen mongrel dogs were chronically instrumented to measure aortic and left ventricular pressures, wall thickness, and left circumflex coronary blood flow (CBF). Before CAO and during CAR, coronary vascular reactivity was investigated by 15-second CAO and subsequent reactive hyperemia (RH) and by the selective intracoronary infusion of acetylcholine (ACh, 10 micrograms/min) and bradykinin (BK, 2.5 micrograms/min), endothelium-dependent vasodilators, and sodium nitroprusside (SNP, 40 micrograms/min), an endothelium-independent vasodilator. CBF responses to ACh and BK began to increase after 6 hours of CAR, reached a peak after 1 to 2 days of CAR, and then subsided over the subsequent 4 days. After 1 day of CAR, compared with before CAO, enhanced CBF responses (P < .05), associated with increased coronary sinus oxygen content, were observed for-ACh (+66 +/- 20%), BK (+74 +/- 24%), and RH (+24 +/- 5%) but not SNP (-2 +/- 10%). Production of NO metabolites (nitrate and nitrite), measured as their coronary arteriovenous differencexCBF, was significantly increased after 1 to 2 days of CAR, both at baseline (153 +/- 56%) and during BK infusion (220 +/- 76%) (P < .05). Holding CBF at pre-CAO levels during the initial CAR period did not attenuate the delayed enhanced endothelial vasodilation to ACh and BK. However, NO blockade with intracoronary NG-nitro-L-arginine blocked the enhanced coronary vasodilation to ACh and BK. Thus, in contrast to previous studies, these data indicate that brief ischemic episodes induce delayed enhanced coronary endothelial function, which is delayed in onset and prolonged in duration. This can be explained by an upregulation of coronary vascular NO production, potentially involved in the mechanism of the delayed window of preconditioning.
Benign-to-Malignant B16 melanoma Progression Induced in Two Stages In Vitro by Exposure to Hypoxi
Authors: C. W. Stackpole, L. Groszek, S. S. Kalbag
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Benign-to-Malignant B16 melanoma Progression Induced in Two Stages In Vitro by Exposure to Hypoxi Get access Christopher W. Stackpole, Christopher W. Stackpole Department of Experimental Pathology, New York Medical CollegeValhalla, N.Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Laura Groszek, Laura Groszek Department of Experimental Pathology, New York Medical CollegeValhalla, N.Y. Search for other works by this author on: Oxford Academic PubMed Google Scholar Suraj S. Kalbag Suraj S. Kalbag * Department of Experimental Pathology, New York Medical CollegeValhalla, N.Y. * Christopher W. Stackpole, Ph.D., Department of Experimental Pathology. Basic Science Building. New York Medical College. Valhalla, NY 10595. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 5, 2 March 1994, Pages 361–367, https://doi.org/10.1093/jnci/86.5.361 Published: 02 March 1994 Article history Received: 02 July 1993 Revision received: 09 November 1993 Accepted: 02 December 1993 Published: 02 March 1994