Myopericarditis in a Korean Young Male With Systemic Lupus Erythematosus

Myocardial involvement with clinical symptoms is a rare manifestation of systemic lupus erythematosus (SLE), despite the relatively high prevalence of myocarditis at autopsies of SLE patients. In this review, we report the case of a 19-year-old male SLE patient who initially presented with myopericarditis and was successfully treated with high dose of glucocorticoids

NF-κB and CREB Are Involved in IL-8 Production of Human Neutrophils Induced by Trichomonas vaginalis-Derived Secretory Products

Trichomonas vaginalis is a flagellated lumen-dwelling extracellular protozoan parasite that causes human trichomoniasis via sexual intercourse. Human neutrophils play a crucial role in acute tissue inflammatory responses in T. vaginalis infection. In this study, we investigated the signaling mechanism of neutrophil responses when stimulated with T. vaginalis-derived secretory products (TvSP), which were collected from 1×107 live trichomonads. Incubation of human neutrophils isolated from peripheral blood with TvSP induced up-regulation of IL-8 protein secretion. In addition, stimulation with TvSP induced phosphorylation of NF-κB and CREB in neutrophils. Moreover, TvSP-induced IL-8 production was also significantly inhibited by pretreatment of neutrophils with iκB inhibitor or CREB inhibitor. These results suggest that transcription factors NF-κB and CREB are involved in IL-8 production in human neutrophils induced by stimulation with T. vaginalis infection

Characteristics, Outcomes and Predictors of Long-Term Mortality for Patients Hospitalized for Acute Heart Failure: A Report From the Korean Heart Failure Registry

BACKGROUND AND OBJECTIVES: Acute heart failure (AHF) is associated with a poor prognosis and it requires repeated hospitalizations. However, there are few studies on the characteristics, treatment and prognostic factors of AHF. The aims of this study were to describe the clinical characteristics, management and outcomes of the patients hospitalized for AHF in Korea. SUBJECTS AND METHODS: We analyzed the clinical data of 3,200 hospitalization episodes that were recorded between June 2004 and April 2009 from the Korean Heart Failure (KorHF) Registry database. The mean age was 67.6±14.3 years and 50% of the patients were female. RESULTS: Twenty-nine point six percent (29.6%) of the patients had a history of previous HF and 52.3% of the patients had ischemic heart disease. Left ventricular ejection fraction (LVEF) was reported for 89% of the patients. The mean LVEF was 38.5±15.7% and 26.1% of the patients had preserved systolic function (LVEF ≥50%), which was more prevalent in the females (34.0% vs. 18.4%, respectively, p<0.001). At discharge, 58.6% of the patients received beta-blockers (BB), 53.7% received either angiotensin converting enzyme-inhibitors or angiotensin receptor blockers (ACEi/ARB), and 58.4% received both BB and ACEi/ARB. The 1-, 2-, 3- and 4-year mortality rates were 15%, 21%, 26% and 30%, respectively. Multivariate analysis revealed that advanced age {hazard ratio: 1.023 (95% confidence interval: 1.004-1.042); p=0.020}, a previous history of heart failure {1.735 (1.150-2.618); p=0.009}, anemia {1.973 (1.271-3.063); p=0.002}, hyponatremia {1.861 (1.184-2.926); p=0.007}, a high level of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) {3.152 (1.450-6.849); p=0.004} and the use of BB at discharge {0.599 (0.360-0.997); p=0.490} were significantly associated with total death. CONCLUSION: We present here the characteristics and prognosis of an unselected population of AHF patients in Korea. The long-term mortality rate was comparable to that reported in other countries. The independent clinical risk factors included age, a previous history of heart failure, anemia, hyponatremia, a high NT-proBNP level and taking BB at discharge.ope

Effects of Interleukin-10 Polymorphisms, Helicobacter pylori Infection, and Smoking on the Risk of Noncardia Gastric Cancer

OBJECTIVE: Both variations in the interleukin-10 (IL10) gene and environmental factors are thought to influence inflammation and gastric carcinogenesis. Therefore, we investigated the associations between IL10 polymorphisms, Helicobacter pylori (H. pylori) infection, and smoking in noncardia gastric carcinogenesis in Koreans. METHODS: We genotyped three promoter polymorphisms (-1082A>G, -819T>C, and -592 A>C) of IL10 in a case-control study of 495 noncardia gastric cancer patients and 495 sex- and age-matched healthy controls. Multiple logistic regression models were used to detect the effects of IL10 polymorphisms, H. pylori infection, and smoking on the risk of gastric cancer, which was stratified by the histological type of gastric cancer. RESULTS: The IL10-819C and -592C alleles were found to have complete linkage disequilibrium, and all three IL10 polymorphisms were associated with an increased risk of intestinal-type noncardia gastric cancer. These associations were observed only in H. pylori-positive subjects and current smokers. A statistically significant interaction between the IL10-592 genotype and H. pylori infection on the risk of intestinal-type gastric cancer was observed (P for interaction  = 0.047). In addition, H. pylori-positive smokers who were carriers of either the IL10-1082G (OR [95% CI]  = 17.76 [6.17-51.06]) or the -592C (OR [95% CI]  = 8.37 [2.79-25.16]) allele had an increased risk of intestinal-type gastric cancer compared to H. pylori-negative nonsmokers homozygous for IL10-1082A and -592A, respectively. The interaction between the IL10-1082 polymorphism and the combined effects of H. pylori infection and smoking tended towards significance (P for interaction  = 0.080). CONCLUSIONS: Inflammation-related genetic variants may interact with H. pylori infection and smoking to increase the risk of noncardia gastric cancer, particularly the intestinal-type. These findings may be helpful in identifying individuals at an increased risk for developing noncardia gastric cancer

Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancers

Background Gynecologic malignancy is one of the leading causes of mortality in female adults worldwide. Comprehensive genomic analysis has revealed a list of molecular aberrations that are essential to tumorigenesis, progression, and metastasis of gynecologic tumors. However, targeting such alterations has frequently led to treatment failures due to underlying genomic complexity and simultaneous activation of various tumor cell survival pathway molecules. A compilation of molecular characterization of tumors with pharmacological drug response is the next step toward clinical application of patient-tailored treatment regimens. Results Toward this goal, we establish a library of 139 gynecologic tumors including epithelial ovarian cancers (EOCs), cervical, endometrial tumors, and uterine sarcomas that are genomically and/or pharmacologically annotated and explore dynamic pharmacogenomic associations against 37 molecularly targeted drugs. We discover lineage-specific drug sensitivities based on subcategorization of gynecologic tumors and identify TP53 mutation as a molecular determinant that elicits therapeutic response to poly (ADP-Ribose) polymerase (PARP) inhibitor. We further identify transcriptome expression of inhibitor of DNA biding 2 (ID2) as a potential predictive biomarker for treatment response to olaparib. Conclusions Together, our results demonstrate the potential utility of rapid drug screening combined with genomic profiling for precision treatment of gynecologic cancers

Three Novel cis-Acting Elements Required for Efficient Plus-Strand DNA Synthesis of the Hepatitis B Virus Genome

Synthesis of the relaxed-circular (RC) DNA genomes of hepadnaviruses by reverse transcriptase involves two template switches during plus-strand DNA synthesis. These template switches require repeat sequences (so-called donor and acceptor sites) between which a complementary strand of nucleic acid is transferred. To determine cis-acting elements apart from the donor and acceptor sites that are required for plus-strand RC DNA synthesis by hepatitis B virus (HBV), a series of mutants bearing a small deletion were made and analyzed for their impact on the viral genome synthesis. We found three novel cis-acting elements in the HBV genome: one element, located in the middle of the minus strand, is indispensable, whereas the other two elements, located near either end of the minus strand, contribute modestly to the plus-strand RC DNA synthesis. The data indicated that the first element facilitates plus-strand RNA primer translocation or subsequent elongation during plus-strand RC DNA synthesis, while the last two elements, although distantly located on the minus strand, act at multiple steps to promote plus-strand RC DNA synthesis. The necessity of multiple cis-acting elements on the minus-strand template reflects the complex nature of hepadnavirus reverse transcription