tbuckley/cabot-search huggingface dataset:
Visceral white fat remodelling contributes to intermittent hypoxia-induced atherogenesis
Authors: L. Poulain, A. Thomas, J. Rieusset, L. Casteilla, P. Levy, C. Arnaud, M. Dematteis
Journal: European Respiratory Journal (2013)

Obstructive sleep apnoea is a highly prevalent disease characterised by repetitive upper airway collapse during sleep leading to intermittent hypoxia. Cardiometabolic complications of sleep apnoea have been mostly attributed to intermittent hypoxia. These consequences could be mediated through intermittent hypoxia-related alterations of the visceral white fat, as it is recognised for playing an important role in inflammation, atherogenesis and insulin resistance. Epididymal adipose tissue alterations were investigated in 20-week-old nonobese male apolipoprotein E-deficient mice exposed to intermittent hypoxia (inspiratory oxygen fraction 5-21%, 60-s cycle, 8 h · day(-1)) or air for 6 weeks. These adipose tissue alterations, as well as metabolic alterations and aortic atherosclerosis, were then assessed in lipectomised or sham-operated mice exposed to intermittent hypoxia or air for 6 weeks. Intermittent hypoxia induced morphological (shrunken adipocytes), functional (increased uncoupling protein-1 expression) and inflammatory (increased macrophage recruitment and secretion of interleukin-6 and tumour necrosis factor-α) remodelling of epididymal adipose tissue. Hypoxic mice presented more severe dyslipidaemia and atherosclerosis lesions and developed insulin resistance. Epididymal lipectomy attenuated both intermittent hypoxia-induced dyslipidaemia and atherogenesis, but did not improve insulin sensitivity. Our results confirmed that the dyslipidaemic and proatherogenic effects of intermittent hypoxia are partly mediated through morphological, functional and inflammatory remodelling of visceral white fat, regardless of obesity.
Human Melanoma Metastases Demonstrate Nonstochastic Site-Specific Antigen Heterogeneity That Correlates with T-cell Infiltration
Authors: Edmund K. Bartlett, Patricia A. Fetsch, Armando C. Filie, Andrea Abati, Seth M. Steinberg, John R. Wunderlich, Donald E. White, Daniel J. Stephens, Francesco M. Marincola, Steven A. Rosenberg, Udai S. Kammula
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Metastasis heterogeneity presents a significant obstacle to the development of targeted cancer therapeutics. In this study, we sought to establish from a large series of human melanoma metastases whether there exists a determined pattern in tumor cellular heterogeneity that may guide the development of future targeted immunotherapies. Experimental Design: From a cohort of 1,514 patients with metastatic melanoma, biopsies were procured over a 17-year period from 3,086 metastatic tumors involving various anatomic sites. To allow specific tumor cell profiling, we used established immunohistochemical methods to perform semiquantitative assessment for a panel of prototypic melanocyte differentiation antigens (MDA), including gp100, MART-1, and tyrosinase. To gain insight into the endogenous host immune response against these tumors, we further characterized tumor cell expression of MHC I and MHC II and, also, the concomitant CD4+ and CD8+ T-cell infiltrate. Results: Tumor cell profiling for MDA expression demonstrated an anatomic site-specific pattern of antigen expression that was highest in brain, intermediate in soft tissues/lymph nodes, and lowest in visceral metastases. Hierarchical clustering analysis supported that melanoma metastases have a phylogenetically determined, rather than a stochastic, pattern of antigen expression that varies by anatomic site. Furthermore, tyrosinase expression was more frequently lost in metastatic sites outside of the brain and was uniquely correlated with both endogenous CD8+ and CD4+ T-cell infiltrates. Conclusion: Site-specific antigen heterogeneity represents a novel attribute for human melanoma metastases that should be considered in future therapy development and when assessing the responsiveness to antigen-specific immunotherapies. Clin Cancer Res; 20(10); 2607–16. ©2014 AACR.
Guidelines of care for office surgical facilities. Part II. Self-Assessment checklist
Authors: None Guidelines/Outcomes Committee, Lynn A Drake, Roger I Ceilley, Raymond L Cornelison, Scott M Dinehart, William Dorner, Robert W Goltz, Gloria F Graham, Maria K Hordinsky, Charles W Lewis, David M Pariser, Stuart J Salasche, John W Skouge, Maria L Chanco Turner, Stephen B Webster, Duane C Whitaker, Barbara Butler, Barbara J Lowery
Journal: Journal of the American Academy of Dermatology (1995)
Risk-Benefit Decision Making for Treatment of Depression During Pregnancy
Authors: Katherine L. Wisner, Deborah A. Zarin, Eric S. Holmboe, Paul S. Appelbaum, Alan J. Gelenberg, Henrietta L. Leonard, Ellen Frank
Journal: American Journal of Psychiatry (2000)

The Committee on Research on Psychiatric Treatments of the American Psychiatric Association identified treatment of major depression during pregnancy as a priority area for improvement in clinical management. The goal of this article was to assist physicians in optimizing treatment plans for childbearing women.The authors' work group developed a decision-making model designed to structure the information delivered to pregnant women in the context of the risk-benefit discussion. Perspectives of forensic and decision-making experts were incorporated.The model directs the psychiatrist to structure the problem through diagnostic formulation and identification of treatment options for depression. Reproductive toxicity in five domains (intrauterine fetal death, physical malformations, growth impairment, behavioral teratogenicity, and neonatal toxicity) is reviewed for the potential somatic treatments. The illness (depression) also is characterized by symptoms of somatic dysregulation that compromise health during pregnancy. The patient actively participates and provides her evaluation of the acceptability of the various treatments and outcomes. Her capacity to participate in this process provides evidence of competence to consent. Included in the decision-making process are the patient's significant others and obstetrical physician. The process is ongoing, with the need for incorporation of additional data as the pregnancy and treatment response progress.The conceptual model provides structure to a process that is frequently stressful for both patients and psychiatrists. By applying the model, clinicians will ensure that critical aspects of the risk-benefit discussion are included in their care of pregnant women.
Serpin Peptidase Inhibitor Clade A Member 1 as a Potential Marker for Malignancy in Insulinomas
Authors: Sandra Valéria de Sá, Maria Lúcia Corrêa-Giannella, Márcio Carlos Machado, Karin Krogh, Madson Queiroz de Almeida, Maria Adelaide Albergaria Pereira, Sheila Aparecida Coelho Siqueira, Rosely Antunes Patzina, Felícia Satie Ibuki, Mari Cleide Sogayar, Marcel Cerqueira César Machado, Daniel Giannella-Neto
Journal: Clinical Cancer Research (2007)

The biological behavior of insulinomas cannot be predicted based on histopathologic criteria in which the diagnosis of malignancy is confirmed by the presence of metastases. In this study, microarray and quantitative real-time reverse transcription-PCR were applied to identify differentially expressed genes between malignant and nonmalignant insulinomas to search for useful biomarkers to recognize the metastatic potential of insulinomas.Code Link human bioarrays were used to analyze differences in approximately 20,000 genes between six well-differentiated endocrine tumors of benign behavior compared with one well-differentiated endocrine carcinoma (WDEC) and three metastases of endocrine carcinomas (MEC). Quantitative real-time reverse transcription-PCR was used to validate differential expressions of five genes in a series of 35 sporadic insulinomas. Serpin peptidase inhibitor clade A member 1 (SERPINA1; alpha-1-antitrypsin) expression, identified as up-regulated in malignant insulinomas, was also evaluated by immunohistochemistry.Analysis of microarray data resulted in 230 differentially expressed genes. Gene Ontology analysis identified serine-type endopeptidase activity and serine-type endopeptidase inhibitor activity as pathways presenting significant differential expression. Protease serine 2 and complement factor B (from serine-type endopeptidase activity pathway) were respectively confirmed as up-regulated in well-differentiated endocrine tumors of benign behavior (WDET) and in WDEC/MEC. Angiotensinogen and SERPINA1 (from serine-type endopeptidase inhibitor activity pathway) were confirmed as up-regulated in WDEC/MEC. SERPINA1 was shown to be expressed in 85.7% of malignant versus 14.3% of nonmalignant insulinomas by immunohistochemistry.Our data are consistent to the possibility that SERPINA1 is a marker of malignancy in insulinomas. Given the widespread availability of antibody anti-alpha-1-antitrypsin in pathology services, SERPINA1 expression evaluation might be of clinical utility in recognizing patients more likely to develop an aggressive presentation.
Relations of Plasma Matrix Metalloproteinase-9 to Clinical Cardiovascular Risk Factors and Echocardiographic Left Ventricular Measures
Authors: Johan Sundström, Jane C. Evans, Emelia J. Benjamin, Daniel Levy, Martin G. Larson, Douglas B. Sawyer, Deborah A. Siwik, Wilson S. Colucci, Patrice Sutherland, Peter W.F. Wilson, Ramachandran S. Vasan
Journal: Circulation (2004)

Plasma levels of matrix metalloproteinase-9 (MMP-9), a key determinant of extracellular matrix degradation, are increased in heart failure and in acute coronary syndromes. We investigated cross-sectional relations of plasma MMP-9 to vascular risk factors and echocardiographic left ventricular (LV) measurements.We studied 699 Framingham Study participants (mean age, 57 years; 58% women), free of heart failure and previous myocardial infarction, who underwent routine echocardiography. We examined sex-specific distributions of LV internal dimensions (LVEDD) and wall thickness (LVWT) and sampled persons with both LVEDD and LVWT below the sex-specific median (referent, n=299), with increased LVEDD (LVEDD > or =90th percentile, n=204) and increased LVWT (LVWT > or =90th percentile, n=221) in a 3:2:2 ratio. Plasma MMP-9 was detectable in 138 persons (20%). In multivariable models, increasing heart rate (OR per SD, 1.41; 95% CI, 1.17 to 1.71) and antihypertensive treatment (OR, 1.63; 95% CI, 1.06 to 2.50) were key clinical correlates of detectable plasma MMP-9. In multivariable-adjusted models, detectable plasma MMP-9 was associated with increased LVEDD (OR, 2.84; 95% CI, 1.13 to 7.11), increased LVWT (OR, 2.54; 95% CI, 1.00 to 6.46), and higher LV mass (P=0.06) in men but not in women (OR for increased LVEDD, 1.37; 95% CI, 0.54 to 3.46; for increased LVWT, 0.99; 95% CI, 0.39 to 2.52; P=0.59 for LV mass).In our community-based sample, detectable plasma MMP-9 levels were associated with increased LV diastolic dimensions and increased wall thickness in men. These observations indicate that plasma MMP-9 level may be a marker for cardiac extracellular matrix degradation, a process involved in LV remodeling.
Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of the Efficacy and Safety of Apricoxib in Combination With Either Docetaxel or Pemetrexed in Patients With Biomarker-Selected Non–Small-Cell Lung Cancer
Authors: Martin J. Edelman, Ming T. Tan, Mary J. Fidler, Rachel E. Sanborn, Greg Otterson, Lecia V. Sequist, Tracey L. Evans, Bryan J. Schneider, Roger Keresztes, John S. Rogers, Jorge Antunez de Mayolo, Josephine Feliciano, Yang Yang, Michelle Medeiros, Sara L. Zaknoen
Journal: Journal of Clinical Oncology (2014)

Overexpression of COX-2 correlates with advanced stage and worse outcomes in non-small-cell lung cancer (NSCLC), possibly as a result of elevated levels of COX-2-dependent prostaglandin E2 (PGE2). Exploratory analyses of studies that used COX-2 inhibitors have demonstrated potentially superior outcome in patients in whom the urinary metabolite of PGE2 (PGE-M) is suppressed. We hypothesized that patients with disease defined by PGE-M suppression would benefit from the addition of apricoxib to second-line docetaxel or pemetrexed.Patients with NSCLC who had disease progression after one line of platinum-based therapy, performance status of 0 to 2, and normal organ function were potentially eligible. Only patients with a ≥ 50% decrease in urinary PGE-M after 5 days of treatment with apricoxib could enroll. Docetaxel 75 mg/m(2) or pemetrexed 500 mg/m(2) once every 21 days per the investigator was administered with apricoxib or placebo 400 mg once per day. The primary end point was progression-free survival (PFS). Exploratory analysis was performed regarding baseline urinary PGE-M and outcomes.In all, 101 patients completed screening, and 72 of the 80 who demonstrated ≥ 50% suppression were randomly assigned to apricoxib or placebo. Toxicity was similar between the arms. No improvement in PFS was seen with apricoxib versus placebo. The median PFS for the control arm was 97 days (95% CI, 52 to 193 days) versus 85 days (95% CI, 67 to 142 days) for the experimental arm (P = .91).Apricoxib did not improve PFS, despite biomarker-driven patient selection.
Tolerability of β-Blocker Initiation and Titration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF)
Authors: Stephen S. Gottlieb, Michael L. Fisher, John Kjekshus, Prakash Deedwania, Lars Gullestad, Jiri Vitovec, John Wikstrand
Journal: Circulation (2002)

Background — β-Blockade improves survival when administered over a long period of time to patients with heart failure. However, the time course of any possible deterioration during the titration phase has not been reported. Methods and Results — We looked at evidence of clinical deterioration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) by analyzing events and symptoms during the first 90 days. During titration, the Kaplan-Meier curves for the combined end point of all-cause mortality/all-cause hospitalization were similar in all patients randomized, with no significant difference in favor of placebo at any visit or in any of the analyzed subgroups (New York Heart Association class II, III/IV, or III/IV with ejection fraction &lt;0.25, heart rate ≤76 bpm, and systolic blood pressure ≤120 mm Hg). The curves started to diverge in favor of β-blockade after 60 days. Low heart rate was the main factor that limited titration. In New York Heart Association class III/IV, 5.9% of the patients receiving placebo discontinued study medicine during the first 90 days compared with 8.1% of those receiving metoprolol CR/XL ( P =0.037 unadjusted, P =NS adjusted); corresponding figures in those with New York Heart Association class III/IV and ejection fraction &lt;0.25 were 7.1% and 8.0% ( P =NS). From day 90 until the end of the study, more patients in the placebo group discontinued study medicine in all subgroups. There was no change in diuretic or ACE inhibitor dosing with β-blocker titration. Most patients reported no change in symptoms of breathlessness or fatigue during the titration phase. Conclusions — When carefully titrated, metoprolol CR/XL can be given safely to the overwhelming majority of patients with stable mild to moderate heart failure, with minimal side effects or deterioration.
Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study
Authors: Eric Bonnefoy, Frédéric Lapostolle, Alain Leizorovicz, Gabriel Steg, Eugène P McFadden, Pierre Yves Dubien, Simon Cattan, Eric Boullenger, Jacques Machecourt, Jean-Michel Lacroute, Jean Cassagnes, François Dissait, Paul Touboul
Journal: The Lancet (2002)
Follow-up Imaging for Vertebral Osteomyelitis
Authors: Adam J. Visconti, Joshua Biddle, Marc Solomon
Journal: JAMA Internal Medicine (2013)

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Systematic Review of the Staging Performance of<sup>18</sup>F-Fluorodeoxyglucose Positron Emission Tomography in Esophageal Cancer
Authors: H.L. van Westreenen, M. Westerterp, P.M.M. Bossuyt, J. Pruim, G.W. Sloof, J.J.B. van Lanschot, H. Groen, J.Th.M. Plukker
Journal: Journal of Clinical Oncology (2004)

Purpose Despite the increasing number of publications concerning 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) for staging of esophageal cancer and the increasing availability of this novel diagnostic modality, its exact role in preoperative staging of these tumors is still unknown. The aim of this study was to systematically review the literature regarding the diagnostic performance of FDG-PET in preoperative staging of patients with esophageal cancer, and to calculate summary estimates of its sensitivity and specificity. Methods The databases of PubMed, Embase, and Cochrane were searched for relevant studies. Two reviewers independently assessed the methodological quality of each study. A meta-analysis of the reported sensitivity and specificity of each study was performed. Results Twelve studies met the inclusion criteria. The studies had several design deficiencies. Pooled sensitivity and specificity for the detection of locoregional metastases were 0.51 (95% CI, 0.34 to 0.69) and 0.84 (95% CI, 0.76 to 0.91), respectively. For distant metastases, pooled sensitivity and specificity were 0.67 (95% CI, 0.58 to 0.76) and 0.97 (95% CI, 0.90 to 1.0), respectively. Conclusion FDG-PET showed moderate sensitivity and specificity for the detection of locoregional metastases, and reasonable sensitivity and specificity in detection of distant lymphatic and hematogenous metastases.
Late Device Dislodgement After Percutaneous Closure of Mitral Prosthesis Paravalvular Leak With Amplatzer Muscular Ventricular Septal Defect Occluder
Authors: Gian Paolo Ussia, Salvatore Scandura, Antonio M. Calafiore, Sara Mangiafico, Rocco Meduri, Alfredo R. Galassi, Corrado Tamburino
Journal: Circulation (2007)
MYCN-Dependent Expression of Sulfatase-2 Regulates Neuroblastoma Cell Survival
Authors: Valeria Solari, Lucia Borriello, Gianluca Turcatel, Hiroyuki Shimada, Richard Sposto, G. Esteban Fernandez, Shahab Asgharzadeh, Edwin A. Yates, Jeremy E. Turnbull, Yves A. DeClerck
Journal: Cancer Research (2014)

Heparan sulfate proteoglycans (HSPG) play a critical role in the interaction of tumor cells and their microenvironment. HSPG activity is dictated by sulfation patterns controlled by sulfotransferases, which add sulfate groups, and sulfatases (Sulf), which remove 6-O-sulfates. Here, we report altered expression of these enzymes in human neuroblastoma cells with higher levels of Sulf-2 expression, a specific feature of MYCN-amplified cells (MYCN-A cells) that represent a particularly aggressive subclass. Sulf-2 overexpression in neuroblastoma cells lacking MYCN amplification (MYCN-NA cells) increased their in vitro survival. Mechanistic investigations revealed evidence of a link between Sulf-2 expression and MYCN pathogenicity in vitro and in vivo. Analysis of Sulf-2 protein expression in 65 human neuroblastoma tumors demonstrated a higher level of Sulf-2 expression in MYCN-A tumors than in MYCN-NA tumors. In two different patient cohorts, we confirmed the association in expression patterns of Sulf-2 and MYCN and determined that Sulf-2 overexpression predicted poor outcomes in a nonindependent manner with MYCN. Our findings define Sulf-2 as a novel positive regulator of neuroblastoma pathogenicity that contributes to MYCN oncogenicity. Cancer Res; 74(21); 5999-6009. ©2014 AACR.
In vitro and in vivo effect of verapamil on human airway responsiveness to leukotriene D4.
Authors: J A Roberts, M A Giembycz, D Raeburn, I W Rodger, N C Thomson
Journal: Thorax (1986)

The mechanism by which leukotriene D4 (LTD4) induces airway narrowing in man is unclear. We have investigated this by examining the effect of the calcium channel blocker verapamil on the sensitivity of in vitro preparations of human bronchi to LTD4 and methacholine, and on the bronchoconstriction induced in normal subjects by these agonists in vivo. In vitro smooth muscle sensitivity was assessed by the concentration of LTD4 and methacholine causing a 50% of maximum contraction (EC50) and as the maximum tension generated. Verapamil did not alter baseline tension or the response to LTD4 but did inhibit contractile responses to methacholine. In vivo studies were performed in six normal subjects; they inhaled increasing concentrations of LTD4 (0.4-50 micrograms/ml) or methacholine (2-64 mg/ml). Airway responsiveness in vivo was expressed as the provocation concentration (PC) of agonist producing a 35% fall in specific airways conductance (PC35sGaw) and a 30% fall in flow at 30% of vital capacity (PC30 V30(p)). Verapamil did not alter baseline sGaw or V30(p). One subject did not respond to LTD4 on either day. In contrast to the in vitro results, verapamil produced a greater than 10 fold reduction in LTD4 induced bronchoconstriction, but had no effect on methacholine induced bronchoconstriction. These results suggest that in normal subjects bronchoconstriction induced by inhaled LTD4 is due to a combination of direct and indirect mechanisms.
Is MRI Really the Gold Standard for the Quantification of Salvage From Myocardial Infarction?
Authors: Philipp Heusch, Felix Nensa, Gerd Heusch
Journal: Circulation Research (2015)

I nfarct size is the major determinant of post myocardial in- farction remodeling and heart failure 1 and ultimately of patients' prognosis. 2,3Infarct size itself is determined by the area at risk, that is, the perfusion territory of the occluded coronary artery, the duration of ischemia, the magnitude of collateral blood flow, and only to a small extent by the hemodynamic situation, notably heart rate. 4The only way to salvage ischemic myocardium from impending infarction is by timely reperfusion; however, reperfusion also inflicts injury on the previously ischemic myocardium and contributes to final infarct size. 5Such reperfusion injury can be attenuated by ischemic conditioning strategies and certain drugs, which recruit part of the signal transduction of ischemic conditioning strategies, 6,7 both in experimental animal models and in patients with reperfused acute myocardial infarction. 8Is MRI Really the Gold Standard for the Quantification of Salvage From Myocardial Infarction?
Pharmacokinetic study of cystemustine, administered on a weekly schedule in cancer patients
Authors: E. Cellarier, C. Terret, P. Labarre, R. Ouabdesselam, H. Curé, C. Marchenay, J.C. Maurizis, J.C. Madelmont, P. Chollet, J.P. Armand
Journal: Annals of Oncology (2002)