University of Pittsburgh

About: University of Pittsburgh is a education organization based out in Pittsburgh, Pennsylvania, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 87042 authors who have published 201012 publications receiving 9656783 citations. The organization is also known as: Pitt & Western University of Pennsylvania.

Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of t-cell function in advanced cancer patients.

Abstract: Impaired T-cell function in patients with advanced cancer has been a widely acknowledged finding, but mechanisms reported thus far are those primarily operating in the tumor microenvironment. Very few mechanisms have been put forth to explain several well-described defects in peripheral blood T cells, such as reduction in expression of signaling molecules, decreased production of cytokines, or increased apoptosis. We have closely examined the peripheral blood mononuclear cell (PBMC) samples derived from patients and healthy individuals, and we have observed an important difference that may underlie the majority of reported defects. We observed that in samples from patients only, an unusually large number of granulocytes copurify with low density PBMCs on a density gradient rather than sediment, as expected, to the bottom of the gradient. We also show that activating granulocytes from a healthy donor with N-formyl-L-methionyl-L-leucyl-L-phenylalanine could also cause them to sediment aberrantly and copurify with PBMCs, suggesting that density change is a marker of their activation. To confirm this, we looked for other evidence of in vivo granulocyte activation and found it in drastically elevated plasma levels of 8-isoprostane, a product of lipid peroxidation and a marker of oxidative stress. Reduced T-cell receptor zeta chain expression and decreased cytokine production by patients' T cells correlated with the presence of activated granulocytes in their PBMCs. We showed that freshly obtained granulocytes from healthy donors, if activated, can also inhibit cytokine production by T cells. This action is abrogated by the addition of the hydrogen peroxide (H(2)O(2)) scavenger, catalase, implicating H(2)O(2) as the effector molecule. Indeed, when added alone, H(2)O(2) could suppress cytokine production of normal T cells. These findings indicate that granulocytes are activated in advanced cancer patients and that granulocyte-derived H(2)O(2) is the major cause of severe systemic T-cell suppression.

Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes.

Abstract: Nitric oxide is a short-lived biologic mediator for diverse cell types. Synthesis of an inducible nitric oxide synthase (NOS) in murine macrophages is stimulated by lipopolysaccharide (LPS) and interferon gamma. In human hepatocytes, NOS activity is induced by treatment with a combination of tumor necrosis factor, interleukin 1, interferon gamma, and LPS. We now report the molecular cloning and expression of an inducible human hepatocyte NOS (hep-NOS) cDNA. hep-NOS has 80% amino acid sequence homology to macrophage NOS (mac-NOS). Like other NOS isoforms, recognition sites for FMN, FAD, and NADPH are present, as well as a consensus calmodulin binding site. NOS activity in human 293 kidney cells transfected with hep-NOS cDNA is diminished by Ca2+ chelation and a calmodulin antagonist, reflecting a Ca2+ dependence not evident for mac-NOS. Northern blot analysis with hep-NOS cDNA reveals a 4.5-kb mRNA in both human hepatocytes and aortic smooth muscle cells following stimulation with LPS and cytokines. Human genomic Southern blots probed with human hep-NOS and human endothelial NOS cDNA clones display different genomic restriction enzyme fragments, suggesting distinct gene products for these NOS isoforms. hep-NOS appears to be an inducible form of NOS that is distinct from mac-NOS as well as brain and endothelial NOS isozymes.

Studying sex and gender differences in pain and analgesia: a consensus report

Abstract: In September 2006, members of the Sex, Gender and Pain Special Interest Group of the International Association for the Study of Pain met to discuss the following: (1) what is known about sex and gender differences in pain and analgesia; (2) what are the "best practice" guidelines for pain research with respect to sex and gender; and (3) what are the crucial questions to address in the near future? The resulting consensus presented herein includes input from basic science, clinical and psychosocial pain researchers, as well as from recognized experts in sexual differentiation and reproductive endocrinology. We intend this document to serve as a utilitarian and thought-provoking guide for future research on sex and gender differences in pain and analgesia, both for those currently working in this field as well as those still wondering, "Do I really need to study females?"

Association Between Initial Use of e-Cigarettes and Subsequent Cigarette Smoking Among Adolescents and Young Adults: A Systematic Review and Meta-analysis.

Abstract: Importance The public health implications of e-cigarettes depend, in part, on whether e-cigarette use affects the risk of cigarette smoking. Objective To perform a systematic review and meta-analysis of longitudinal studies that assessed initial use of e-cigarettes and subsequent cigarette smoking. Data Sources PubMed, EMBASE, Cochrane Library, Web of Science, the 2016 Society for Research on Nicotine and Tobacco 22nd Annual Meeting abstracts, the 2016 Society of Behavioral Medicine 37th Annual Meeting & Scientific Sessions abstracts, and the 2016 National Institutes of Health Tobacco Regulatory Science Program Conference were searched between February 7 and February 17, 2017. The search included indexed terms and text words to capture concepts associated with e-cigarettes and traditional cigarettes in articles published from database inception to the date of the search. Study Selection Longitudinal studies reporting odds ratios for cigarette smoking initiation associated with ever use of e-cigarettes or past 30-day cigarette smoking associated with past 30-day e-cigarette use. Searches yielded 6959 unique studies, of which 9 met inclusion criteria (comprising 17 389 adolescents and young adults). Data Extraction and Synthesis Study quality and risk of bias were assessed using the Newcastle-Ottawa Scale and the Risk of Bias in Non-randomized Studies of Interventions tool, respectively. Data and estimates were pooled using random-effects meta-analysis. Main Outcomes and Measures Among baseline never cigarette smokers, cigarette smoking initiation between baseline and follow-up. Among baseline non–past 30-day cigarette smokers who were past 30-day e-cigarette users, past 30-day cigarette smoking at follow-up. Results Among 17 389 adolescents and young adults, the ages ranged between 14 and 30 years at baseline, and 56.0% were female. The pooled probabilities of cigarette smoking initiation were 23.2% for baseline ever e-cigarette users and 7.2% for baseline never e-cigarette users. The pooled probabilities of past 30-day cigarette smoking at follow-up were 21.5% for baseline past 30-day e-cigarette users and 4.6% for baseline non–past 30-day e-cigarette users. Adjusting for known demographic, psychosocial, and behavioral risk factors for cigarette smoking, the pooled odds ratio for subsequent cigarette smoking initiation was 3.50 (95% CI, 2.38-5.16) for ever vs never e-cigarette users, and the pooled odds ratio for past 30-day cigarette smoking at follow-up was 4.28 (95% CI, 2.52-7.27) for past 30-day e-cigarette vs non–past 30-day e-cigarette users at baseline. A moderate level of heterogeneity was observed among studies ( I2 = 56%). Conclusions and Relevance e-Cigarette use was associated with greater risk for subsequent cigarette smoking initiation and past 30-day cigarette smoking. Strong e-cigarette regulation could potentially curb use among youth and possibly limit the future population-level burden of cigarette smoking.