Objective and designT helper 17 (Th17) and regulatory T (Treg) lymphocytes might play important roles in patients with severe sepsis. The association of Th17 or Treg lymphocytes with survival is also unclear.MethodsEighty-seven patients with severe sepsis were enrolled from our intensive care units between August 2008 and July 2010. Leukocyte antigens and clinical data were determined on day 1 in all patients and on day 7 in first-year patients.ResultsThe percentages in peripheral blood mononuclear cells (PBMCs) and circulatory counts of CD4+ and CD8+ lymphocytes in survivors were higher than those in non-survivors. Th1/CD4+ ratios and circulatory Th1 lymphocyte counts in survivors were higher than in non-survivors. Absolute counts of Th17 and Treg lymphocytes in survivors were higher than in non-survivors. The percentages of CD4+ and CD8+ in survivors’ PBMCs were increased after 6 days. Th17/CD4+ ratios and circulatory Th17 lymphocyte counts in survivors were increased after 6 days.ConclusionsHigher Th1 differentiation and total CD4+ T lymphocyte counts were associated with higher survival. The association of circulatory Th17 and Treg lymphocytes with mortality in severe sepsis may be due to the change in total CD4+ T lymphocytes. In survivors, Th17 differentiation and counts were restored.

Pulmonary artery aneurysm is a rare lesion of the thoracic cavity. Different etiologies have been reviewed, but idiopathic lesions without other symptoms are seldom reported. Usually, surgical interventions are suggested, but the long-term outcomes are not well established. Here, we report a 24-year-old man with main pulmonary artery aneurysm who successfully underwent aneurysmectomy and polytetrafluoroethylene vascular graft replacement. The postoperative course was uneventful, and the following image study revealed normal size of the great vessels.

IntroductionSepsis-induced immunosuppression may result in death. The mechanisms of immune suppression include loss of macrophage and monocyte expression of the major histocompatibility complex, increased anti-inflammatory cytokine expression and decreased expression of proinflammatory cytokines. In this study, we sought to determine the mechanisms of immune suppression in severe sepsis by repeated detection.MethodsWe designed this prospective observational study to measure monocyte human leukocyte antigen (HLA)-DR expression, plasma cytokine levels and cytokine responses on days 1 and 7 in stimulated peripheral blood mononuclear cells (PBMCs) of healthy controls and patients with severe sepsis.ResultsOf the 35 enrolled patients, 23 survived for 28 days and 12 died, 6 of whom died within 7 days. Plasma levels of IL-1β, IL-6, IL-10, IL-17, transforming growth factor (TGF)-β1 and TNF-α were higher, but plasma IL-12 level was lower in septic patients than those in controls. Day 1 plasma levels of IL-1β, IL-6, IL-10 and TGF-β1 in nonsurvivors were higher than those in survivors. Day 7 plasma IL-10 levels in nonsurvivors were higher than in survivors. IL-1β response was higher, but IL-12 and TNF-α responses were lower in septic patients than in controls. Day 1 IL-6 response was lower, but day 1 TGF-β1 response was higher in nonsurvivors than in survivors. Plasma IL-6 and IL-10 levels were decreased in survivors after 6 days. IL-6 response was decreased in survivors after 6 days, but IL-12 response was increased. Monocyte percentage was higher, but positive HLA-DR percentage in monocytes and mean fluorescence intensity (MFI) of HLA-DR were lower in septic patients than in controls. MFI of HLA-DR was increased in survivors after 6 days.ConclusionsMonocyte HLA-DR expression and IL-12 response from PBMCs are restored in patients who survive severe sepsis.

Alcohol’s impairment of both hepatic lipid metabolism and insulin resistance (IR) are key drivers of alcoholic steatosis, the initial stage of alcoholic liver disease (ALD). Pharmacologic reduction of lipotoxic ceramide prevents alcoholic steatosis and glucose intolerance in mice, but potential off-target effects limit its strategic utility. Here, we employed a hepatic-specific acid ceramidase (ASAH) overexpression model to reduce hepatic ceramides in a Lieber-DeCarli model of experimental alcoholic steatosis. We examined effects of alcohol on hepatic lipid metabolism, body composition, energy homeostasis, and insulin sensitivity as measured by hyperinsulinemic-euglycemic clamp. Our results demonstrate that hepatic ceramide reduction ameliorates the effects of alcohol on hepatic lipid droplet (LD) accumulation by promoting VLDL secretion and lipophagy, the latter of which involves ceramide cross-talk between the lysosomal and LD compartments. We additionally demonstrate that hepatic ceramide reduction prevents alcohol’s inhibition of hepatic insulin signaling. These effects on the liver are associated with a reduction in oxidative stress markers and are relevant to humans, as we observe peri- LD ASAH expression in human ALD. Together, our results suggest a potential role for hepatic ceramide inhibition in preventing ALD.

Background: Many determinants for a sustained response to lamivudine therapy have been reported but the role of T cell responsiveness remains unclear. The finding that tyrosine-methionine-aspartate-aspartate (YMDD) motif of the reverse transcriptase domain of hepatitis B virus (HBV) DNA polymerase carries a HLA-A2 restricted cytotoxic T lymphocyte (CTL) epitope makes quantitative measurement of the numbers of peptide specific CTLs feasible using MHC tetramer-peptide complex staining. Aim: To investigate the correlation between anti-YMDD motif CTL activity and the efficacy of lamivudine therapy in HLA-A2 positive patients with chronic hepatitis B (CH-B). Methods: The function and phenotype of peptide and interleukin 2 expanded peripheral blood mononuclear cells were quantified by cell lytic assay and immunocytochemical analysis by staining with HLA-A2-peptide tetramer complexes. Results: After in vitro expansion, sustained responders had more potent CTL responses against YMDD, YVDD, and YIDD, as well as other epitopes on HBV antigens than non-responders. The frequency of YMDD/YVDD/YIDD motif specific CTLs increased significantly with an effective cell lytic function during and after therapy in sustained responders but not in non-responders. YMDD specific CTLs cross reacted with YIDD and YVDD mutant epitopes, and shared T cell receptor gene usages with YIDD and YVDD specific CTLs. Conclusions: Sustained responders, at least HLA-A2 patients, elicited a more potent CTL immunity against YMDD and its mutants. YMDD specific CTLs are cross reactive with YVDD and YIDD mutant epitopes, which may further contribute to immune clearance of the mutant viruses and a successful response to lamivudine therapy in CH-B patients.