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        Adipose Tissue Dendritic Cells Are Independent Contributors to Obesity-Induced Inflammation and Insulin Resistance

        Cho, Kae Won,Zamarron, Brian F.,Muir, Lindsey A.,Singer, Kanakadurga,Porsche, Cara E.,DelProposto, Jennifer B.,Geletka, Lynn,Meyer, Kevin A.,O’Rourke, Robert W.,Lumeng, Carey N. American Association of Immunologists 2016 Journal of Immunology Vol. No.

        <P>Dynamic changes of adipose tissue leukocytes, including adipose tissue macrophage (ATM) and adipose tissue dendritic cells (ATDCs), contribute to obesity-induced inflammation and metabolic disease. However, clear discrimination between ATDC and ATM in adipose tissue has limited progress in the field of immunometabolism. In this study, we use CD64 to distinguish ATM and ATDC, and investigated the temporal and functional changes in these myeloid populations during obesity. Flow cytometry and immunostaining demonstrated that the definition of ATM as F4/80(+)CD11b(+) cells overlaps with other leukocytes and that CD45(+)CD64(+) is specific for ATM. The expression of core dendritic cell genes was enriched in CD11c(+)CD64(-) cells (ATDC), whereas core macrophage genes were enriched in CD45(+)CD64(+) cells (ATM). CD11c(+)CD64(-) ATDCs expressed MHC class II and costimulatory receptors, and had similar capacity to stimulate CD4(+) T cell proliferation as ATMs. ATDCs were predominantly CD11b(+) conventional dendritic cells and made up the bulk of CD11c(+) cells in adipose tissue with moderate high-fat diet exposure. Mixed chimeric experiments with Ccr2(-/-) mice demonstrated that high-fat diet induced ATM accumulation from monocytes was dependent on CCR2, whereas ATDC accumulation was less CCR2 dependent. ATDC accumulation during obesity was attenuated in Ccr7(-/-) mice and was associated with decreased adipose tissue inflammation and insulin resistance. CD45(+)CD64(+) ATM and CD45(+)CD64(-)CD11c(+) ATDCs were identified in human obese adipose tissue and ATDCs were increased in s.c. adipose tissue compared with omental adipose tissue. These results support a revised strategy for unambiguous delineation of ATM and ATDC, and suggest that ATDCs are independent contributors to adipose tissue inflammation during obesity.</P>

      • KCI등재

        Sarcopenia and Post-Operative Morbidity and Mortality in Patients with Gastric Cancer

        Stephen O Brien,Maria Twomey,Fiachra Moloney,Richard G. Kavanagh,Brian W. Carey,Derek Power,Michael M. Maher,Owen J. OConnor,Criostoir ÓSúilleabháin 대한위암학회 2018 Journal of gastric cancer Vol.18 No.3

        Purpose: Surgical resection for gastric adenocarcinoma is associated with significant post-operative morbidity and mortality. The aim of this study was to assess the prognostic significance of sarcopenia in patients undergoing resection for gastric adenocarcinoma with respect to post-operative morbidity and survival. Materials and Methods: A retrospective analysis was conducted on a cohort of consecutive patients who underwent surgical resection for gastric adenocarcinoma between 2008 and 2014. Patient demographics, radiological parameters, and pathological data were collected. OsiriX software (Pixmeo) was used to measure skeletal muscle area, which was normalized for height to calculate skeletal muscle index. Results: A total of 56 patients (41 male, 15 female; mean age, 68.4 ± 11.9 years) met the inclusion criteria. Of these, 36% (20 of 56) of the patients were sarcopenic pre-operatively. Both sarcopenic and non-sarcopenic patient groups were equally matched with the exception of weight and body mass index (P=0.036 and 0.001, respectively). Sarcopenia was associated with a decreased overall survival (log-rank P=0.003) and was an adverse prognostic predictor of overall survival in multivariate analysis (hazard ratio, 10.915; P=0.001). Sarcopenia was a predictor of serious in-hospital complications in multivariate analysis (odds ratio, 3.508; P=0.042). Conclusions: In patients undergoing curative resection for gastric cancer, there was a statistically significant association between sarcopenia and both decreased overall survival and serious post-operative complications. The measurement and reporting of skeletal muscle index on pre-operative computed tomography should be considered.

      • SCOPUSKCI등재

        Sarcopenia and Post-Operative Morbidity and Mortality in Patients with Gastric Cancer

        O'Brien, Stephen,Twomey, Maria,Moloney, Fiachra,Kavanagh, Richard G.,Carey, Brian W.,Power, Derek,Maher, Michael M.,O'Connor, Owen J.,O'Suilleabhain, Criostoir The Korean Gastric Cancer Association 2018 Journal of gastric cancer Vol.18 No.3

        Purpose: Surgical resection for gastric adenocarcinoma is associated with significant post-operative morbidity and mortality. The aim of this study was to assess the prognostic significance of sarcopenia in patients undergoing resection for gastric adenocarcinoma with respect to post-operative morbidity and survival. Materials and Methods: A retrospective analysis was conducted on a cohort of consecutive patients who underwent surgical resection for gastric adenocarcinoma between 2008 and 2014. Patient demographics, radiological parameters, and pathological data were collected. OsiriX software (Pixmeo) was used to measure skeletal muscle area, which was normalized for height to calculate skeletal muscle index. Results: A total of 56 patients (41 male, 15 female; mean age, $68.4{\pm}11.9years$) met the inclusion criteria. Of these, 36% (20 of 56) of the patients were sarcopenic pre-operatively. Both sarcopenic and non-sarcopenic patient groups were equally matched with the exception of weight and body mass index (P=0.036 and 0.001, respectively). Sarcopenia was associated with a decreased overall survival (log-rank P=0.003) and was an adverse prognostic predictor of overall survival in multivariate analysis (hazard ratio, 10.915; P=0.001). Sarcopenia was a predictor of serious in-hospital complications in multivariate analysis (odds ratio, 3.508; P=0.042). Conclusions: In patients undergoing curative resection for gastric cancer, there was a statistically significant association between sarcopenia and both decreased overall survival and serious post-operative complications. The measurement and reporting of skeletal muscle index on pre-operative computed tomography should be considered.

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