Outer membrane protein a of Salmonella enterica serovar Typhimurium activates dendritic cells and enhances Th1 polarization

<p>Abstract</p> <p>Background</p> <p>Typhoid, which is caused by <it>Salmonella enterica </it>serovar Typhimurium, remains a major health concern worldwide. Multidrug-resistant strains of <it>Salmonella </it>have emerged which exhibit increased survivability and virulence, thus leading to increased morbidity. However, little is known about the protective immune response against this microorganism. The outer membrane protein (Omp)A of bacteria plays an important role in pathogenesis.</p> <p>Results</p> <p>We purified OmpA from <it>S. enterica </it>serovar Typhimurium (OmpA-sal) and characterized the role of OmpA-sal in promoting adaptive and innate immune responses. OmpA-sal functionally activated bone marrow-derived dendritic cells by augmenting expression of CD80, CD86, and major histocompatibility complex classes I and II. Interestingly, OmpA-sal induced production of interferon-γ from T cells in mixed lymphocyte reactions, thus indicating Th1-polarizing capacity. The expression of surface markers and cytokine production in dendritic cells was mediated by the TLR4 signaling pathway in a TLR4 Knock-out system.</p> <p>Conclusions</p> <p>Our findings suggest that OmpA-sal modulates the adaptive immune responses to <it>S. enterica </it>serovar Typhimurium by activating dendritic cells and driving Th1 polarization, which are important properties to consider in the development of effective <it>S. enterica </it>serovar Typhimurium vaccines and immunotherapy adjuvant.</p

Association of Low-Dose Exposure to Persistent Organic Pollutants with Global DNA Hypomethylation in Healthy Koreans

BACKGROUND: Global DNA methylation levels have been reported to be inversely associated with blood levels of persistent organic pollutants (POPs), xenobiotics that accumulate in adipose tissue. Whether these associations extend to a population with much lower concentrations of POPs is not known. OBJECTIVES: This study was performed to examine whether low-dose exposure to POPs was associated with global DNA hypomethylation in Koreans. METHODS: The amount of global DNA by hypomethylation was estimated by the percent 5-methyl-cytosine (%5-mC) in Alu and LINE-1 assays in 86 apparently healthy Koreans. Among various POPs, organochlorine (OC) pesticides, polychlorinated bipheryls (PCBs), and polybrominated dipherylethers (PBDEs) were measured. RESULTS: Most OC pesticides were inversely and significantly associated with %5-mC in the Alu assay, with correlation coefficients in the range -0.2 to -0.3 after adjusting for age, sex, body mass index, smoking, and alcohol. The strongest OC pesticide associations with %5-mC in the Alu assay were observed with oxychlordane, trans-nonachlor, and p,p&apos;-dichlorodiphenyldichloroethylene. The correlation coefficient of age with %5-mC in the Alu assay was -0.24, similar to correlations of OC pesticides with %5-mC in the Alu assay. Most PCBs and PBDEs showed nonsignificant inverse trends with %5-mC in the Alu assay, but for some PCBs the U-shaped association was significant. On the other hand, POPs were not associated with %5-mC in the LINE-1 assay. CONCLUSIONS: We found that low-dose exposure to Pops, in particular OC pesticides, was associated with global DNA hypomethylation in apparently healthy Koreans.open1195102sciescopu

Psychometric Properties of the Hypomania Checklist-32 in Korean Patients with Mood Disorders

OBJECTIVE The aim of this study was to examine the validity of the Korean version of the Hypomania Checklist-32, second revision (HCL-32-R2) in mood disorder patients. METHODS A total of 454 patients who diagnosed as mood disorder according to Structured Clinical Interview for DSM-IV Axis I Disorders, clinician version (SCID-CV) (bipolar disorder [BD] I, n=190; BD-II, n=72; and major depressive disorder [MDD], n=192) completed the Korean module of the HCL-32-R2 (KHCL-32-R2). RESULTS The KHCL-32-R2 showed a three-factorial structure (eigenvalue ＞2) that accounted for 43.26% of the total variance. Factor 1 was labeled "active/elated" and included 16 items; factor 2, "irritable/distractible" and included 9 items; and factor 3 was labeled "risk-taking/indulging" and included 9 items. A score of 16 or more on the KHCL-32-R2 total scale score distinguished between BD and MDD, which yielded a sensitivity of 70% and a specificity of 70%. MDD and BD-II also could be differentiated at a cut-off of 15 with maximized sensitivity (0.67) and specificity (0.66). Cronbach's alpha of KHCL-32-R2 and its subsets (factors 1, 2, and 3) were 0.91, 0.89, 0.81 and 0.79, respectively. Correlations between KHCL-32-R2 and Montgomery- Asberg Depression Rating Scale, Young Mania Rating Scale and Korean version of Mood Disorder Questionnaire were -0.66 (p=0.41), -0.14 (p=0.9), and 0.61 (p＜0.001), respectively. CONCLUSION The KHCL-32-R2 may be a useful tool in distinguishing between bipolar and depressive patients in clinical settings

Multiple Intracranial Tuberculomas Mimicking Granulocytic Sarcomas in Acute Myeloid Leukemia

The diagnosis of incracranial tuberculoma in immune-compromised hosts is often difficult because conventional magnetic resonance (MR) imaging of tuberculoma reveals various findings and neurologic symptoms are not typical. Here, we report a case of a 54-yr old man with multiple intracranial tuberculoma who was treated for acute myeloid leukemia. He complained of right-side paresthesia after the third consolidation chemotherapy without leukemic relapse and fever. MR imaging of the brain showed multiple ring-enhanced lesions in the cerebrum, cerebellar hemisphere, and pons. The lesions appeared to mimic a metastatic tumor or abscess. Cerebrospinal fluid analysis showed no abnormal cells, but the level of adenosine deaminase was elevated (28.8 IU/L, normal 0-8). Stereotactic brain biopsy was performed, but only reactive gliosis was observed. To confirm diagnosis, an open brain biopsy was performed. The histopathology demonstrated chronic granulomatous inflammation with caseous necrosis. Tuberculous-polymerase chain reaction of the biopsy showed a positive result. He was treated with anti-tuberculosis medication and a high dose of steroid. Paresthesia improved, and follow-up brain MR imaging showed the decreased size and numbers of ring-enhanced lesions and improvement of perilesional edema 1 month after treatment. Here, we report on an interesting case of intracranial tuberculoma in acute myeloid leukemia

Enhancement of paclitaxel-induced breast cancer cell death via the glycogen synthase kinase-3 beta-mediated B-cell lymphoma 2 regulation

Glycogen synthase kinase-3 beta (GSK-3 beta) is a serine/threonine protein kinase that is known to mediate cancer cell death. Here, we show that B-cell lymphoma 2 (Bcl-2), an anti-apoptotic protein, is regulated by GSK-3 beta and that GSK-3 beta-mediated regulation of Bcl-2 is crucial for mitochondrial-dependent cell death in paclitaxel-stimulated cells. We demonstrate that MCF7 GSK3 beta siRNA cells are more sensitive to cell death than MCF7 GFP control cells and that in the absence of GSK-3 beta, Bcl-2 levels are reduced, a result enhanced by paclitaxel. Paclitaxel-induced JNK (c-Jun N-terminal kinase) activation is critical for Bcl-2 modulation. In the absence of GSK-3 beta, Bcl-2 was unstable in an ubiquitination-dependent manner in both basal-and paclitaxel-treated cells. Furthermore, we demonstrate that GSK-3 beta-mediated regulation of Bcl-2 influences cytochrome C release and mitochondrial membrane potential. Taken together, our data suggest that GSK-3 beta-dependent regulation of Bcl-2 is crucial for mitochondria-dependent cell death in paclitaxel-mediated breast cancer therapy.clos

The Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein, a toll-like receptor 4 agonist, enhances dendritic cell-based cancer vaccine potency

In this study, we showed the direct interaction between Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein (FAP) and toll-like receptor4 (TLR4) via co-localization and binding by using confocal microscopy and co-immunoprecipitation assays. FAP triggered the expression of pro- and anti-inflammatory cytokines in a TLR4-dependent manner. In addition, FAP-induced cytokine expression in bone marrow-derived dendritic cells (BMDCs) was modulated in part by glycogen synthase kinase-3 (GSK-3). FAP-induced expression of CD80, CD86, major histocompatibility complex (MHC) class I, and MHC class II in TLR4+/+ BMDCs was not observed in TLR4-/- BMDCs. Furthermore, FAP induced DC-mediated CD8+ T cell proliferation and cytotoxic T lymphocyte (CTL) activity, and suppressed tumor growth with DC-based tumor vaccination in EG7 thymoma murine model. Taken together, these results indicate that the TLR4 agonist, FAP, a potential immunoadjuvant for DC-based cancer vaccination, improves the DC-based immune response via the TLR4 signaling pathway

Randomized Trial of Stents Versus Bypass Surgery for Left Main Coronary Artery Disease 5-Year Outcomes of the PRECOMBAT Study

AbstractBackgroundIn a previous randomized trial, we found that percutaneous coronary intervention (PCI) was not inferior to coronary artery bypass grafting (CABG) for the treatment of unprotected left main coronary artery stenosis at 1 year.ObjectivesThis study sought to determine the 5-year outcomes of PCI compared with CABG for the treatment of unprotected left main coronary artery stenosis.MethodsWe randomly assigned 600 patients with unprotected left main coronary artery stenosis to undergo PCI with a sirolimus-eluting stent (n = 300) or CABG (n = 300). The primary endpoint was a major adverse cardiac or cerebrovascular event (MACCE: a composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target vessel revascularization) and compared on an intention-to-treat basis.ResultsAt 5 years, MACCE occurred in 52 patients in the PCI group and 42 patients in the CABG group (cumulative event rates of 17.5% and 14.3%, respectively; hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 0.84 to 1.90; p = 0.26). The 2 groups did not differ significantly in terms of death from any cause, myocardial infarction, or stroke as well as their composite (8.4% and 9.6%; HR, 0.89; 95% CI, 0.52 to 1.52; p = 0.66). Ischemia-driven target vessel revascularization occurred more frequently in the PCI group than in the CABG group (11.4% and 5.5%, respectively; HR: 2.11; 95% CI: 1.16 to 3.84; p = 0.012).ConclusionsDuring 5 years of follow-up, our study did not show significant difference regarding the rate of MACCE between patients who underwent PCI with a sirolimus-eluting stent and those who underwent CABG. However, considering the limited power of our study, our results should be interpreted with caution. (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease [PRECOMBAT]; NCT00422968

Effectiveness and safety of adalimumab in patients with intestinal Behçets disease: a real-world prospective observational study in South Korea

Background Intestinal Behçets disease (BD) is characterized by typical gastrointestinal ulcers in patients with BD followed by complications such as bleeding, perforation and fistula. Biologic agents are currently under active investigation to delay the disease course. Various data regarding infliximab are available, but there is relatively lack of data regarding adalimumab. Methods This was a multicenter, real-world prospective observational study to evaluate the effectiveness and safety of adalimumab in intestinal BD. The primary endpoint was disease activity at each follow up, including disease activity index for intestinal Behçets disease (DAIBD), serum C-reactive protein (CRP) level, and endoscopic findings. The secondary endpoint was the incidence of adverse drug reactions (ADRs). Results A total of 58 patients were enrolled and 8 of them were excluded. Adverse events were reported in 72.0% of patients with 122 events. ADRs were reported in 24.0% with 28 events. For adverse events, arthralgia was most commonly reported (13.1%: 16/122) and only one experienced critical adverse event (0.82%, 1/122: death due to stroke). On multivariable regression analysis, a longer disease duration was significantly associated with decreased ADRs [Odds ratio 0.976 (0.953–0.999, 95% CI); p = 0.042]. Clinical response rates as assessed by DAIBD were 90.9% at Week 12 and 89.7% at Week 56, respectively. The mean serum CRP level at baseline was significantly decreased after 12 weeks (3.91 ± 4.93 to 1.26 ± 2.03 mg/dL; p = 0.0002). Conclusion Adalimumab was found to be safe and effective in Korean patients with intestinal BD. A longer disease duration was significantly associated with decreased ADRs