tbuckley/cabot-search huggingface dataset:
Effects of peroxisome proliferator-activated receptor-γ agonists on the generation of microparticles by monocytes/macrophages
Authors: Tommaso Neri, Cinzia Cordazzo, Yuri Carmazzi, Silvia Petrini, Cristina Balìa, Fabio Stefanelli, Angela Amoruso, Sandra Brunelleschi, Maria Cristina Breschi, Roberto Pedrinelli, Pierluigi Paggiaro, Alessandro Celi
Journal: Cardiovascular Research (2012)

Microparticles are membrane vesicles shed by cells upon activation and/or apoptosis. Microparticles are involved in several processes, including blood coagulation and thrombosis. In addition to their role in the regulation of lipid metabolism, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists exert other effects, both dependent on and independent of PPAR-γ activation. Some PPAR-γ agonists have been linked to an increased risk of thrombotic diseases. We aimed to investigate the potential role of PPAR-γ agonists on the generation of procoagulant microparticles by human monocytes/macrophages. Monocytes/macrophages were isolated from the buffy coats of normal donors. Cells were incubated with three structurally unrelated PPAR-γ agonists, namely, rosiglitazone, pioglitazone, and 15-deoxy-Δ12,14-prostaglandin J2. Microparticle generation was assessed as phosphatidylserine concentration by a prothrombinase assay, after capturing the microparticles onto annexin V-coated wells. Intracellular calcium concentration was assessed by a fluorescent probe. Extracellular signal-regulated kinase (ERK) phosphorylation was assessed by western blot. Tissue factor expression on microparticles was measured with a one-stage clotting assay. Rosiglitazone and 15-deoxy-Δ12,14-prostaglandin J2, but not pioglitazone, caused a dose-dependent, significant increase in intracellular calcium mobilization and tissue factor-bearing microparticle generation. EGTA inhibited microparticle generation. The specific PPAR-γ inhibitor, GW9662, also inhibited microparticle generation. Finally, rosiglitazone and 15-deoxy-Δ12,14-prostaglandin J2 caused phosphorylation of ERK; inhibition of ERK by PD98059 inhibited microparticle generation. The PPAR-γ agonists rosiglitazone and 15-deoxy-Δ12,14-prostaglandin J2, but not pioglitazone, caused an increase in procoagulant, tissue factor-bearing microparticle generation by human monocytes/macrophages. The effect was dependent on ERK phosphorylation and partly mediated through intracellular calcium mobilization; however, direct activation of the PPAR-γ ligand was also involved.
The nose and OSA: variable nasal obstruction may be more important in pathophysiology than fixed obstruction
Authors: W. T. McNicholas
Journal: European Respiratory Journal (2008)

<h3>Abstract</h3> <h3>Objective</h3> To examine the effect of face mask intervention in respiratory infections across different exposure settings and age groups. <h3>Design</h3> Systematic review and meta-analysis. <h3>Data sources</h3> PubMed, Cochrane Central Register of Controlled Trials, and Web of Science were searched for randomized controlled trials investigating the effect of face masks on respiratory infections published by November 18th, 2020. We followed PRISMA guidelines. <h3>Eligibility criteria for selecting studies</h3> Randomized controlled trials investigating face masks in respiratory infections across different exposure settings. Two reviewers performed the search, extracted data, and assessed the risk of bias. Random effects meta-analysis with risk ratio, adjusted odds ratios, and number needed to treat were performed. Findings by source control or wearer protection, age groups, exposure settings, and role of non-compliance were evaluated. <h3>Results</h3> Seventeen studies were included, (N=11,601 cases and N=10,286 controls, follow-up from 4 days to 19 months). Fourteen trials included adults and children and three trials included children only. Twelve studies showed non-compliance in treatment and eleven in control group. Four studies supported the use of face masks. Meta-analysis across all studies with risk ratios found no association with number of infections (RR=0.957 [0.810 − 1.131], p=0.608). Meta-analysis using odds ratios adjusted for age, sex, and vaccination (when available) showed protective effect of face masks (OR=0.850 [0.736 − 0.982], p=0.027). Subgroup meta-analysis with adjusted odds ratios found a decrease in respiratory infections among adults (14 studies, OR = 0.829 [0.709 − 0.969], p=0.019) in source control setting (OR = 0.845 [0.7375 − 0.969], p=0.0159) and when face masks were used together with hand hygiene OR = 0.690 [0.568 − 0.838], p=0.0002). Overall between-study heterogeneity was large also in the subgroup analyses. <h3>Conclusion</h3> Despite the large between study heterogeneity, compliance bias and differences by environmental settings, the findings support the use of face masks to prevent respiratory infections. <i>PROSPERO registration number CRD42020205523</i>.
Postoperative radiotherapy in completely resected, early-stage, non-small-cell lung cancer: reflections and future directions.
Authors: Pierluigi Granone, Steven Keller, Lucio Trodella, Alfredo Cesario, Stefano Margaritora, Venanzio Porziella, Salvatore Valente, Giuseppe Maria Corbo, Rolando Maria d'Angelillo
Journal: The Lancet Oncology (2002)
Association of Habitual Snoring with Glucose and Insulin Metabolism in Nonobese Korean Adult Men
Authors: Chol Shin, JinYoung Kim, JeHyeong Kim, SangYeub Lee, JaeJeong Shim, KwangHo In, KyungHo Kang, SeHwa Yoo, NamHan Cho, KuChan Kimm, SoonJae Joo
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Habitual snoring is associated with cardiovascular morbidity and mortality, and metabolic abnormalities such as impaired glucose homeostasis. Many studies were performed in obese Western populations. The purpose of this study was to examine the association of habitual snoring with glucose and insulin metabolism in nonobese Korean men who were free of diabetes and hypertension. A total of 2,719 men ages 40-69 years from the Korean Health and Genome Study participated in this study. Information of snoring frequency was obtained by a questionnaire and glucose and insulin levels during oral glucose tolerance test were measured. Repeated measures analysis of variance detected significant differences in the changing patterns of glucose and insulin levels at 1 hour and 2 hours between habitual snorers and nonhabitual snorers, whereas there were no significant differences in fasting blood glucose and insulin levels. Multivariate logistic regression analyses revealed that habitual snoring was independently associated with elevated 1-hour and 2-hour glucose levels and a 2-hour insulin level, respectively. The present data suggest that habitual snoring may affect glucose-insulin metabolism, independent of diabetes and hypertension, even in nonobese Korean middle-age men. Further prospective studies are needed to examine the causal relationship between habitual snoring and insulin resistance or glucose intolerance.
Estrogen Receptors α and β Mediate Contribution of Bone Marrow–Derived Endothelial Progenitor Cells to Functional Recovery After Myocardial Infarction
Authors: Hiromichi Hamada, Myeong Kon Kim, Atsushi Iwakura, Masaaki Ii, Tina Thorne, Gangjian Qin, Jun Asai, Yoshiaki Tsutsumi, Haruki Sekiguchi, Marcy Silver, Andrea Wecker, Evelyn Bord, Yan Zhu, Raj Kishore, Douglas W. Losordo
Journal: Circulation (2006)

Background— Estradiol (E 2 ) modulates the kinetics of circulating endothelial progenitor cells (EPCs) and favorably affects neovascularization after ischemic injury. However, the roles of estrogen receptors α (ERα) and β (ERβ) in EPC biology are largely unknown. Methods and Results— In response to E 2 , migration, tube formation, adhesion, and estrogen-responsive element–dependent gene transcription activities were severely impaired in EPCs obtained from ERα-knockout mice (ERαKO) and moderately impaired in ERβKO EPCs. The number of ERαΚΟ EPCs (42.4±1.5; P &lt;0.001) and ERβKO EPCs (55.4±1.8; P =0.03) incorporated into the ischemic border zone was reduced as compared with wild-type (WT) EPCs (72.5±1.3). In bone marrow transplantation (BMT) models, the number of mobilized endogenous EPCs in E 2 -treated mice was significantly reduced in ERαKO BMT (WT mice transplanted with ERαKO bone marrow) (2.03±0.18%; P =0.004 versus WT BMT) and ERβKO BMT (2.62±0.07%; P =0.02 versus WT) compared with WT BMT (2.87±0.13%) (WT to WT BMT as control) mice. Capillary density at the border zone of ischemic myocardium also was significantly reduced in ERαKO BMT and ERβKO BMT compared with WT mice (WT BMT, 1718±75/mm 2 ; ERαKO BMT, 1107±48/mm 2 ; ERβKO BMT, 1567±50/mm 2 ). ERα mRNA was expressed more abundantly on EPCs compared with ERβ. Moreover, vascular endothelial growth factor was significantly downregulated on ERαKO EPCs compared with WT EPCs both in vitro and in vivo. Conclusions— Both ERα and ERβ contribute to E 2 -mediated EPC activation and tissue incorporation and to preservation of cardiac function after myocardial infarction. ERα plays a more prominent role in this process. Moreover, ERα contributes to upregulation of vascular endothelial growth factor, revealing possible mechanisms of an effect of E 2 on EPC biology. Finally, these data provide additional evidence of the importance of bone marrow–derived EPC phenotype in ischemic tissue repair.
Weight Loss to Treat Urinary Incontinence in Overweight and Obese Women
Authors: Leslee L. Subak, Rena Wing, Delia Smith West, Frank Franklin, Eric Vittinghoff, Jennifer M. Creasman, Holly E. Richter, Deborah Myers, Kathryn L. Burgio, Amy A. Gorin, Judith Macer, John W. Kusek, Deborah Grady
Journal: New England Journal of Medicine (2009)

Obesity is an established and modifiable risk factor for urinary incontinence, but conclusive evidence for a beneficial effect of weight loss on urinary incontinence is lacking. We randomly assigned 338 overweight and obese women with at least 10 urinary-incontinence episodes per week to an intensive 6-month weight-loss program that included diet, exercise, and behavior modification (226 patients) or to a structured education program (112 patients). The mean (+/-SD) age of the participants was 53+/-11 years. The body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) and the weekly number of incontinence episodes as recorded in a 7-day diary of voiding were similar in the intervention group and the control group at baseline (BMI, 36+/-6 and 36+/-5, respectively; incontinence episodes, 24+/-18 and 24+/-16, respectively). The women in the intervention group had a mean weight loss of 8.0% (7.8 kg), as compared with 1.6% (1.5 kg) in the control group (P<0.001). After 6 months, the mean weekly number of incontinence episodes decreased by 47% in the intervention group, as compared with 28% in the control group (P=0.01). As compared with the control group, the intervention group had a greater decrease in the frequency of stress-incontinence episodes (P=0.02), but not of urge-incontinence episodes (P=0.14). A higher proportion of the intervention group than of the control group had a clinically relevant reduction of 70% or more in the frequency of all incontinence episodes (P<0.001), stress-incontinence episodes (P=0.009), and urge-incontinence episodes (P=0.04). A 6-month behavioral intervention targeting weight loss reduced the frequency of self-reported urinary-incontinence episodes among overweight and obese women as compared with a control group. A decrease in urinary incontinence may be another benefit among the extensive health improvements associated with moderate weight reduction. (ClinicalTrials.gov number, NCT00091988.)
IN VITRO GENERATION OF MEMORY LYMPHOCYTES REACTIVE TO TRANSPLANTATION ANTIGENS
Authors: Nurit Hollander, Haim Ginsburg, Michael Feldman
Journal: The Journal of Experimental Medicine (1974)

The in vitro generation of memory cells reactive to transplantation antigens is described. Blast cells, obtained from rat lymphocytes sensitized on xenogeneic or allogeneic fibroblast monolayers, reverted to secondary small lymphocytes after transfer from the foreign sensitizing to syngeneic monolayers. These secondary small lymphocytes had a limited in vitro life span of 4-6 wk. They manifested properties of memory cells: upon re-exposure to fibroblasts of the sensitizing phenotype, the secondary lymphocytes adhered to the fibroblast monolayer and transformed into blast cells with cytotoxic activity. The response of secondary lymphocytes was rapid, compared to that of normal lymphocytes, and directed specifically against the primary sensitizing antigens.
Cognitive Effects of Atypical Antipsychotic Medications in Patients With Alzheimer's Disease: Outcomes From CATIE-AD
Authors: Cheryl L.P. Vigen, Wendy J. Mack, Richard S.E. Keefe, Mary Sano, David L. Sultzer, T. Scott Stroup, Karen S. Dagerman, John K. Hsiao, Barry D. Lebowitz, Constantine G. Lyketsos, Pierre N. Tariot, Ling Zheng, Lon S. Schneider
Journal: American Journal of Psychiatry (2011)

Objective: The impact of the atypical antipsychotics olanzapine, quetiapine, and risperidone on cognition in patients with Alzheimer's disease is unclear. The authors assessed the effects of time and treatment on neuropsychological functioning during the Clinical Antipsychotic Trials of Intervention Effectiveness–Alzheimer's Disease study (CATIE-AD). Method: CATIE-AD included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior who were randomly assigned to receive masked, flexible-dose olanzapine, quetiapine, risperidone, or placebo. Based on their clinicians' judgment, patients could discontinue the originally assigned medication and receive another randomly assigned medication. Patients were followed for 36 weeks, and cognitive assessments were obtained at baseline and at 12, 24, and 36 weeks. Outcomes were compared for 357 patients for whom data were available for at least one cognitive measure at baseline and one follow-up assessment that took place after they had been on their prescribed medication or placebo for at least 2 weeks. Results: Overall, patients showed steady, significant declines over time in most cognitive areas, including in scores on the Mini-Mental State Examination (MMSE; –2.4 points over 36 weeks) and the cognitive subscale of the Alzheimer's Disease Assessment Scale (–4.4 points). Cognitive function declined more in patients receiving antipsychotics than in those given placebo on multiple cognitive measures, including the MMSE, the cognitive subscale of the Brief Psychiatric Rating Scale, and a cognitive summary score summarizing change on 18 cognitive tests. Conclusions: In CATIE-AD, atypical antipsychotics were associated with worsening cognitive function at a magnitude consistent with 1 year's deterioration compared with placebo. Further cognitive impairment is an additional risk of treatment with atypical antipsychotics that should be considered when treating patients with Alzheimer's disease.
Humoral immune response to the E2 protein of hepatitis G virus is associated with long-term recovery from infection and reveals a high frequency of hepatitis G virus exposure among healthy blood donors
Authors: M Tacke, S Schmolke, V Schlueter, S Sauleda, J I Esteban, E Tanaka, K Kiyosawa, H J Alter, U Schmitt, G Hess, B Ofenloch-Haehnle, A M Engel
Journal: Hepatology (1997)

The second envelope protein (E2) of the hepatitis G virus (HGV) was expressed in Chinese hamster ovary (CHO) cells and showed a molecular weight of approximately 60 to 70 kd, with 15 to 25 kd of the size contributed by N-linked glycosylation. An enzyme-linked immunosorbent assay (ELISA) using HGV-E2 was developed to test for antibodies to this protein (anti-E2) in human sera. High sensitivity was achieved by developing monoclonal antibodies (mAbs) to HGV-E2, which were used as capture antibodies in the ELISA. Our studies revealed that 16% of healthy Spanish blood donors were exposed to HGV, indicating that additional routes of viral transmission besides parenteral exposure might exist. An even higher prevalence of exposure to HGV (52%-73%) was found in several groups at risk of parenteral exposure to infectious agents, i.e., intravenous drug users, transfusion history, hemophiliacs, and hepatitis C virus (HCV)-positive patients. Most anti-E2-positive patients were HGV-RNA-negative and vice versa, indicating an inverse correlation of these two viral markers. A panel of 16 posttransfusion patients followed for up to 16 years revealed that patients who develop an anti-E2 response become HGV-RNA-negative, while patients who do not develop anti-E2 are persistently infected. Immunity to HGV seems to be long-lasting, because circulating antibody to E2 could still be detected 14 years after seroconversion. Sequence comparisons showed that E2 is highly conserved among isolates collected worldwide, indicating that immune escape variants are not common in HGV infections. This reflects on a molecular level why HGV infections usually are cleared spontaneously by the host. However, possible mechanisms of HGV persistence, as found in some patients, remain to be elucidated.
Thymidylate synthase protein expression in colorectalcancer metastases predicts for clinical outcome to leucovorin-modulated bolus or infusional 5-fluorouracil but not methotrexate-modulated bolus 5-fluorouracil
Authors: C. Aschele, D. Debernardis, R. Bandelloni, S. Cascinu, V. Catalano, P. Giordani, S. Barni, D. Turci, G. Drudi, S. Lonardi, L. Gallo, F. Maley, S. Monfardini
Journal: Annals of Oncology (2002)
Changes in Prandial Glucagon Levels After a 2-Year Treatment With Vildagliptin or Glimepiride in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy
Authors: Bo Ahrén, James E. Foley, Ele Ferrannini, David R. Matthews, Bernard Zinman, Sylvie Dejager, Vivian A. Fonseca
Journal: Diabetes Care (2010)

To determine if the dipeptidyl peptidase-4 inhibitor vildagliptin more effectively inhibits glucagon levels than the sulfonylurea glimepiride during a meal.Glucagon responses to a standard meal were measured at baseline and study end point (mean 1.8 years) in a trial evaluating add-on therapy to metformin with 50 mg vildagliptin b.i.d. compared with glimepiride up to 6 mg q.d. in type 2 diabetes (baseline A1C 7.3 +/- 0.6%).A1C and prandial glucose area under the curve (AUC)(0-2 h) were reduced similarly in both groups, whereas prandial insulin AUC(0-2 h) increased to a greater extent by glimepiride. Prandial glucagon AUC(0-2 h) (baseline 66.6 +/- 2.3 pmol . h(-1) . l(-1)) decreased by 3.4 +/- 1.6 pmol . h(-1) . l(-1) by vildagliptin (n = 137) and increased by 3.8 +/- 1.7 pmol . h(-1) . l(-1) by glimepiride (n = 121). The between-group difference was 7.3 +/- 2.1 pmol . h(-1) . l(-1) (P < 0.001).Vildagliptin therapy but not glimepiride improves postprandial alpha-cell function, which persists for at least 2 years.
Selective Endothelin-A Versus Combined Endothelin-A/Endothelin-B Receptor Blockade in Rat Chronic Heart Failure
Authors: Paul Mulder, Houssaine Boujedaini, Vincent Richard, Genevieve Derumeaux, Jean Paul Henry, Sylvanie Renet, Jerry Wessale, Terry Opgenorth, Christian Thuillez
Journal: Circulation (2000)

Background —The relative efficacy of endothelin-A (ET A ) receptor blockade versus combined ET A -ET B receptor blockade in chronic heart failure (CHF) is still largely unknown. Methods and Results —We compared, in a rat model of CHF (coronary ligation), the hemodynamic and structural effects of 1 month of treatment with the ET A antagonist ABT-627 (5 mg · kg −1 · d −1 ), the ET B antagonist A-192621 (30 mg · kg −1 · d −1 ) or a combination of the 2 drugs. Doses were chosen for their capacity to block the pressor response to ET-1 (for ET A blockade) or the depressor responses to sarafotoxin S6c or ET-1 (for ET B blockade). ET A and combined ET A -ET B blockade reduced systolic blood pressure to the same extent, whereas ET B blockade had no effect. In contrast, only combined ET A -ET B blockade significantly reduced heart rate. Both ET A and combined ET A -ET B blockade, but not ET B blockade alone, increased left ventricular (LV) fractional shortening and wall thickening and reduced LV end-diastolic pressure, as well as LV end-diastolic and end-systolic volumes. However, all treatments (including ET B blockade) decreased LV collagen accumulation. Conclusions —The chronic blockade of both ET A and ET B receptors improved systemic hemodynamics, as well as LV function and remodeling, to the same extent as ET A receptor blockade alone. However, only combined ET A -ET B receptor blockade decreased heart rate. Whether this differential effect on heart rate affects the long-term outcome after treatment with ET A or mixed ET A -ET B antagonists in CHF remains to be determined.
Role of Kinins in the Control of Renal Papillary Blood Flow, Pressure Natriuresis, and Arterial Pressure
Authors: Jerónimo Tornel, María Isabel Madrid, Miguel García-Salom, Klaus J. Wirth, Francisco J. Fenoy
Journal: Circulation Research (2000)

Abstract —The present study evaluated the effects of blocking kinins with the bradykinin B 2 receptor antagonist Hoe140 on the relationship between renal perfusion pressure, papillary blood flow (PBF), and sodium excretion. To determine the relevance of renal kinins in the long-term control of arterial pressure, the effect of a chronic intrarenal infusion of Hoe140 on arterial pressure and sodium balance was also studied. PBF was not autoregulated in volume-expanded rats, and the administration of Hoe140 reduced PBF (−30%) and improved PBF autoregulation. The kinin antagonist also decreased sodium excretion (−35%) and blunted pressure natriuresis with no whole-kidney renal hemodynamic changes. These effects may be mediated through nitric oxide (NO), because in rats pretreated with N G -nitro- l -arginine methyl ester, Hoe140 had no additional effects on PBF or pressure natriuresis. A role for NO in mediating the renal response to Hoe140 is also supported by the finding that Hoe140 reduced basal urinary NO 3 − /NO 2 − excretion (−33%), and it blunted the arterial pressure–induced increase in NO 3 − /NO 2 − excretion, which is compatible with the idea that the pressure-natriuresis response may be mediated through kinins and NO. The importance of kinins in long-term regulation of arterial pressure is demonstrated by the severe arterial hypertension (172±6 mm Hg) induced during the chronic intrarenal infusion of Hoe140 associated with sodium and volume retention. These data suggest that renal kinins and NO may be a part of the renal mechanism coupling changes in arterial pressure with modifications in PBF and sodium excretion, therefore contributing to the long-term control of arterial pressure.