Background The benefit of statin use after acute ST-segment elevation myocardial infarction (STEMI) has been well established, however, the influence of the timing of statin administration has not been elucidated. The objective of this study focused on early clinical outcomes after percutaneous coronary intervention (PCI). Methods This analysis of the Korea Working Group on Myocardial Infarction registry (KorMI) study included 3,584 STEMI patients (mean age, 63 ±13 years;male, 2,684, 74.9%) undergoing PCI from January 2008 to June 2009. Rates of major adverse cardiac events (MACE:all-cause death, recurrent MI, and target lesion revascularization) were compared among patients grouped according to statin therapy timing:I, both during and after hospitalization (n=2,653, 74%);II, only during hospita-lization (n=309, 8.6%);III, only after discharge (n=157, 4.4%);and IV, no statin therapy (n=465, 13%). Mean follow-up duration was 234 ± 113 days. Results Multivariate factors of statin use during hospitalization included prior statin use, multiple diseased vessels, final thrombolysis in myocardial infarction flow grade III, and low-density lipoprotein cholesterol level. At 6-month follow-up, groups III and IV had the highest MACE rates (2.3%, 3.9%, 5.1%, and 4.9%for groups I-IV, respectively, P=0.004). After adjusting for confounders, groups II-IV had a higher MACE risk than group I [hazard ratio (HR):3.20, 95%confidence interval (95%CI):1.31-7.86, P=0.011;HR:3.84, 95%CI:1.47-10.02, P=0.006;and HR:3.17, 95%CI:1.59-6.40, P=0.001;respectively]. Conclusions This study, based on the national registry database, shows early and continuous statin therapy improvs early outcomes of STEMI patients after PCI in real-world clinical prac-tice.

Syntenin is an adaptor molecule containing 2 PDZ domains which mediate molecular interactions with diverse integral or cytoplasmic proteins. Most of the results on the biological function of syntenin were obtained from studies with malignant cells, necessitating exploration into the role of syntenin in normal cells. To understand its role in normal cells, we investigated expression and function of syntenin in human lymphoid tissue and cells in situ and in vitro. Syntenin expression was denser in the germinal center than in the extrafollicular area. Inside the germinal center, syntenin expression was obvious in follicular dendritic cells (FDCs). Flow cytometric analysis with isolated cells confirmed a weak expression of syntenin in T and B cells and a strong expression in FDCs. In FDC-like cells, HK cells, most syntenin proteins were found in the cytoplasm compared to weak expression in the nucleus. To study the function of syntenin in FDC, we examined its role in the focal adhesion of HK cells by depleting syntenin by siRNA technology. Knockdown of syntenin markedly impaired focal adhesion kinase phosphorylation in HK cells. These results suggest that syntenin may play an important role in normal physiology as well as in cancer pathology.
B-Lymphocytes ; Cytoplasm ; Dendritic Cells, Follicular* ; Focal Adhesion Protein-Tyrosine Kinases* ; Focal Adhesions* ; Germinal Center ; Humans* ; Lymphoid Tissue ; PDZ Domains ; Phosphorylation ; Proteins ; RNA, Small Interfering ; Syntenins*

Objective Multidector computed tomography (MDCT) is now commonly used for the evaluation of coronary artery disease. Because MDCT images include many non-cardiac organs and the patient population evaluated is highly susceptible to extracardiac diseases, this study was designed to evaluate the prevalence of extracardiac findings in the MDCT evaluation of ischemic heart disease. Methods From March 2007 to March 2008, a total of six-hundred twenty patients, who underwent 64-slice MDCT evaluations for chest pain, or dyspnea, were enrolled in this study. Cardiac and non-cardiac findings were comprehensively evaluated by a radiologist. Results Enrolled patients included 306 men (49.4%), with a mean age of 66 years. Significant coronary artery stenosis was found in 41.6%of the patients. A total of 158 extracardiac findings were observed in 110 (17.7%) patients. Commonly involved extracardiac organs were lung (36.7%), hepatobiliary system (21.5%), thyroid (19.6%), kidney (10.8%), spine (9.7%) and breast (0.6%). Of those 110 patients, 50 (45.5%) patients underwent further diagnostic investigations. Malignant disease was detected in three (2.7%) patients (lung cancer, pancreatic cancer, and thyroid cancer). Conclusions Extracardiac findings are frequently present and should be a concern in the MDCT evaluation of chest pain syndrome.

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays an important role in vascular functions, including vasorelaxation. We here investigated the pharmacological effect of the natural product syringaresinol on vascular relaxation and eNOS-mediated NO production as well as its underlying biochemical mechanism in endothelial cells. Treatment of aortic rings from wild type, but not eNOS-/- mice, with syringaresinol induced endothelium-dependent relaxation, which was abolished by addition of the NOS inhibitor NG-monomethyl-L-arginine. Treatment of human endothelial cells and mouse aortic rings with syringaresinol increased NO production, which was correlated with eNOS phosphorylation via the activation of Akt and AMP kinase (AMPK) as well as elevation of intracellular Ca2+ levels. A phospholipase C (PLC) inhibitor blocked the increases in intracellular Ca2+ levels, AMPK-dependent eNOS phosphorylation, and NO production, but not Akt activation, in syringaresinol-treated endothelial cells. Syringaresinol-induced AMPK activation was inhibited by co-treatment with PLC inhibitor, Ca2+ chelator, calmodulin antagonist, and CaMKKbeta siRNA. This compound also increased eNOS dimerization, which was inhibited by a PLC inhibitor and a Ca2+-chelator. The chemicals that inhibit eNOS phosphorylation and dimerization attenuated vasorelaxation and cGMP production. These results suggest that syringaresinol induces vasorelaxation by enhancing NO production in endothelial cells via two distinct mechanisms, phosphatidylinositol 3-kinase/Akt- and PLC/Ca2+/CaMKKbeta-dependent eNOS phosphorylation and Ca2+-dependent eNOS dimerization.
Animals ; Aorta/*drug effects/physiology ; Enzyme Activation/drug effects ; Furans/*pharmacology ; Gene Deletion ; Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; Humans ; Lignans/*pharmacology ; Mice ; Mice, Inbred C57BL ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/genetics/*metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide Phospholipase C/metabolism ; Phosphorylation/drug effects ; Protein Multimerization/*drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; Vasodilation/*drug effects

BACKGROUND: Prostaglandins (PGs) play pathogenic and protective roles in inflammatory diseases. The novel concept of PGs as immune modulators is being documented by several investigators. By establishing an in vitro experimental model containing human follicular dendritic cell-like cells, HK cells, we reported that HK cells produce prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2) and that these PGs regulate biological functions of T and B cells. METHODS: To investigate the respective contribution of cyclooxygenase-1 (COX-1) and COX-2 to PGE2 and PGI2 production in HK cells, we performed siRNA technology to knock down COX enzymes and examined the effect on PG production. RESULTS: Both PGE2 and PGI2 productions were almost completely inhibited by the depletion of COX-2. In contrast, COX-1 knockdown did not significantly affect PG production induced by lipopolysaccharide (LPS). CONCLUSION: The current results suggest that mPGES-1 and PGIS are coupled with COX-2 but not with COX-1 in human follicular dendritic cell (FDC) and may help understand the potential effects of selective COX inhibitors on the humoral immunity.
Cyclooxygenase 1 ; Cyclooxygenase 2 ; Dendritic Cells, Follicular ; Dinoprostone ; Epoprostenol ; Humans ; Immunity, Humoral ; Intramolecular Oxidoreductases ; Models, Theoretical ; Prostaglandins ; Research Personnel ; RNA, Small Interfering ; Stromal Cells

The immune system maintains the integrity of our bodies by warding off intruding microorganisms, but by sustaining tolerance to our own tissues. The immunologic tolerance is established by several layers of safeguards, including physical elimination of self-reactive lymphocytes during their development in the central lymphoid organs, anergy induction in autoreactive lymphocytes before their emigration to the periphery, or production regulatory T lymphocytes that suppress the activation, proliferation, and differentiation of various effector cells. The major regulatory T lymphocytes display their phenotype as CD4(+)CD25(+)Foxp3(+) and constitute about 10% of the peripheral T lymphocytes. Even with these safeguards, the immunologic tolerance sometimes fails and generates autoimmune diseases. Scientists studying the pathogenesis of autoimmune diseases pay particular attention to a CD4(+) T lymphocytes subset, Th17 lymphocytes, distinct from Th1 and Th2. Th17 produces diverse proinflammatory cytokines including IL-17 and TNF-alpha. Th17 and these cytokines are causatively associated with many episodes of autoimmune diseases. Accumulated data reveal the critical role of Th17 cells in the pathology of autoimmunity and portray them as an important target in the treatment of various autoimmune diseases. In this article, we will describe the main characteristics of regulatory T cells and Th17 cells and their cellular and molecular mechanisms of protective or destructive functions, respectively.
Autoimmune Diseases ; Autoimmunity ; Cytokines ; Emigration and Immigration ; Immune System ; Interleukin-17 ; Lymphocytes ; Phenotype ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Th17 Cells ; Tumor Necrosis Factor-alpha

The immune system maintains the integrity of our bodies by warding off intruding microorganisms, but by sustaining tolerance to our own tissues. The immunologic tolerance is established by several layers of safeguards, including physical elimination of self-reactive lymphocytes during their development in the central lymphoid organs, anergy induction in autoreactive lymphocytes before their emigration to the periphery, or production regulatory T lymphocytes that suppress the activation, proliferation, and differentiation of various effector cells. The major regulatory T lymphocytes display their phenotype as CD4(+)CD25(+)Foxp3(+) and constitute about 10% of the peripheral T lymphocytes. Even with these safeguards, the immunologic tolerance sometimes fails and generates autoimmune diseases. Scientists studying the pathogenesis of autoimmune diseases pay particular attention to a CD4(+) T lymphocytes subset, Th17 lymphocytes, distinct from Th1 and Th2. Th17 produces diverse proinflammatory cytokines including IL-17 and TNF-alpha. Th17 and these cytokines are causatively associated with many episodes of autoimmune diseases. Accumulated data reveal the critical role of Th17 cells in the pathology of autoimmunity and portray them as an important target in the treatment of various autoimmune diseases. In this article, we will describe the main characteristics of regulatory T cells and Th17 cells and their cellular and molecular mechanisms of protective or destructive functions, respectively.
Autoimmune Diseases ; Autoimmunity ; Cytokines ; Emigration and Immigration ; Immune System ; Interleukin-17 ; Lymphocytes ; Phenotype ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Th17 Cells ; Tumor Necrosis Factor-alpha

BACKGROUND: Platelets take part in repairing the lesions of endothelial damage. To understand the molecular mechanism of this process, we tested the hypothesis that CD154 expressed on activated platelets stimulates proliferation of human endothelial cells. METHODS: The expression levels of CD154 and CD40 on platelets and endothelial cells, respectively, were measured by flow cytometry and confocal microscopy. Function-blocking monoclonal antibody against CD154 was developed after immunization with CD154- transfected L cells. RESULTS: An anti-CD40 agonist antibody and soluble CD154 both induced significant proliferation of endothelial cells. In addition, a function-blocking anti-CD154 antibody inhibited the platelet-induced proliferation of endothelial cells, indicating that the CD154-CD40 pathway is involved in these cellular interactions. An anti-VEGF antibody failed to inhibit the proliferation. This, in addition to the fact that very small amounts of VEGF are released from platelets or endothelial cells, suggests that VEGF does not play an important role in the platelet-stimulated proliferation of endothelial cells. CONCLUSION: Our results indicate that platelets induce proliferation of endothelial cells by CD154-CD40 interactions independently of VEGF.
Blood Platelets ; Endothelial Cells ; Flow Cytometry ; Human Umbilical Vein Endothelial Cells ; Humans ; Immunization ; Microscopy, Confocal ; Vascular Endothelial Growth Factor A

PURPOSE: This study aimed to contribute to overall public health by examining the prevalence rates of impaired fasting blood glucose and type 2 diabetes mellitus and developing a model to predict high risk factors for impaired fasting blood glucose and type 2 diabetes mellitus. METHODS: The 1998 Public Health Nutrition Survey data was used for this study. Subjects were 7,702 adult at the age of 20 or over. The frequency analysis, chisquared test was performed. A decision tree was utilized to define a model designed to predict high risk factors for impaired fasting glucose and type 2 diabetes mellitus. RESULTS: The prevalence rates of impaired fasting blood glucose was 10.8% and prevalence rates of type 2 diabetes mellitus was 9.4%. The decision tree analysis exhibited that age was strong factors for impaired fasting blood glucose. HDL cholesterol and kind of economic activities were high risk factors for impaired fasting blood glucose and type 2 diabetes mellitus on those in 20s. BMI, total cholesterol level, marriage status, sex for impaired fasting blood glucose and type 2 diabetes mellitus on those in 30s. The total cholesterol level, drinking and waist size were identified as risk factors on those in 40s. BMI, education level and hypertension seemed to have an impact on those in 50s. The waist size, sex and income had an impact on those in 60s. CONCLUSIONS: This study underscores the need for the public health infrastructure to improve various health promotion programs for those who have risk factors for impaired fasting blood glucose and type 2 diabetes mellius. The implementation of effective nutrition, workout and anti-drinking programs will boost public health.
Adult ; Blood Glucose ; Cholesterol ; Cholesterol, HDL ; Decision Trees ; Diabetes Mellitus, Type 2* ; Drinking ; Education ; Fasting* ; Glucose* ; Health Promotion ; Humans ; Hypertension ; Marriage ; Nutrition Surveys ; Prevalence ; Public Health ; Risk Factors*

PURPOSE: We report six cases of histologically diagnosed conjunctival MALT (mucosa-associated lymphoid tissue)oma. Presenting symptoms were eyelid swelling, foreign body sensation, lid mass, injection and itching sensation. PATIENTS AND METHODS: Six patients with conjunctival MALToma were followed. Clinical progress and biopsy result were reviewed periodically. RESULTS: The conjunctival MALToma seemed to be localized and slowly progressive. Although the conjunctival MALToma is known to be well responsive to radiotherapy, two of three patients who received radiotherapy revealed to have remnant lymphoma cells histologically in conjunctival biopsy. In addition, chemotherapy did not have curative effect in any of the patients. CONCLUSIONS: Therefore, we are doubtful for the necessity of active treatment in MALTomas of the conjunctiva.
Biopsy ; Conjunctiva ; Drug Therapy ; Eyelids ; Foreign Bodies ; Humans ; Lymphoma ; Pruritus ; Radiotherapy ; Sensation