Identification of novel variants for complicating cardiac disease in the scrub typhus infection using whole genome sequencing

Background/Aims@#Scrub typhus infection has been known to complicate cardiovascular diseases mainly attributing to high mortality. Genetic susceptibility loci for complicating cardiac diseases such as atrial fibrillation, heart failure, and ischemic heart disease identified by genomic study have been limited in scrub typhus infection. Therefore, we investigated the genetic novel variants predicting complicating cardiac diseases in patients with confirmed scrub typhus infection using whole genome sequencing. @*Methods@#We performed a prospective study for eight consecutive patients with scrub typhus infection. During follow-up, six cases were clinically diagnosed with complicating cardiac diseases and two controls without complicating cardiac diseases. The whole genomes of the all patients were sequenced, and the individual sequence variants were compared between accordcase and control patients. Variant genotypes were compared and identified as a single nucleotide polymorphism (SNP) of the different genotype distributions between six cases and two controls. @*Results@#The GG genotype in SNP (rs4977397) of solute carrier 24 family member 2 (SLC24A2) gene and non-TT genotype in SNP (rs2676750) of adenosine deaminase, RNA specific, B2 (ADARB2) gene were distinctively found in the case patients with complicated cardiac disease, compared with control patents in the scrub typhus infection. @*Conclusions@#We suggest that the SNPs of SLC24A2 and ADARB2 might be genetic surrogate markers for complicating cardiac diseases in the scrub typhus infection. Our study show that early detection based on individual sequence variants might be feasible to predict complicating cardiac diseases in patients with scrub typhus infection, if further studies with more participants confirm these findings.

Surgically Metabolic Resection of Pericardial Fat to Ameliorate Myocardial Mitochondrial Dysfunction in Acute Myocardial Infarction Obese Rats

Background@#Pericardial fat (PF) is highly associated with cardiovascular disease but the effectiveness of surgical resection of PF is still unknown for myocardial mitochondrial structure and function in acute myocardial infarction (AMI) with obesity. The aim of this study was to demonstrate the difference in myocardial mitochondrial structure and function between obese AMI with additionally resected PF and those without resected PF. @*Methods@#Obese rats with 12-week high fat diet (45 kcal% fat, n = 21) were randomly assigned into 3 groups: obese control, obese AMI and obese AMI with additionally resected PF. One week after developing AMI and additional resection of PF, echocardiogram, myocardial mitochondrial histomorphology, oxidative phosphorylation system (OXPHOS), anti-oxidative enzyme and sarcoplasmic reticulum Ca 2+ ATPase 2 (SERCA2) in the non-infarcted area were assessed between these groups. @*Results@#There was significant improvement of systolic function in AMI with PF resection compared with the AMI group in the echocardiogram. Even though the electron microscopic morphology for the mitochondria seems to be similar between the AMI with PF resection and AMI groups, there was an improved expression of PGC-1α and responsive OXPHOS including NDUFB3, NDUFB5 and SDHB are associated with the ATP levels in the AMI with PF resection compared with those in the AMI group. In addition, the expression levels of antioxidant enzymes (MnSOD) and SERCA2 were improved in the AMI with PF resection compared with those in the AMI group. @*Conclusion@#Surgical resection of PF might ameliorate myocardial mitochondria dysfunction in obese AMI.

Relaxin Receptor RXFP1 and RXFP2 Expression in Ligament, Tendon, and Shoulder Joint Capsule of Rats

Numerous musculoskeletal disorders are caused by thickened ligament, tendon stiffness, or fibrosis of joint capsule. Relaxin, a peptide hormone, can exert collagenolytic effect on ligamentous and fibrotic tissues. We hypothesized that local injection of relaxin could be used to treat entrapment neuropathy and adhesive capsulitis. Because hormonal effect depends on the receptor of the hormone on the target cell, it is important to confirm the presence of such hormonal receptor at the target tissue before the hormone therapy is initiated. The aim of this study was to determine whether there were relaxin receptors in the ligament, tendon, and joint capsular tissues of rats and to identify the distribution of relaxin receptors in these tissues. Transverse carpal ligaments (TCLs), inguinal ligaments, anterior cruciate ligaments (ACLs), Achilles tendons, and shoulder joint capsules were obtained from male Wistar rats. Western blot analysis was used to identify relaxin receptor isoforms RXFP1 and RXFP2. The distribution of relaxin receptors was determined by immunohistochemical staining. The RXFP1 isoform was found in all tissues examined. The RXFP2 isoform was present in all tissues but the TCLs. Its expression in ACLs tissues was relatively weak compared to that in other tissues. Our results revealed that RXFP1 and RXFP2 were distributed in distinctly different patterns according to the type of tissue (vascular endothelial cells, fibroblast-like cells) they were identified.

17Beta-estradiol Stimulates Glucose Uptake Through Estrogen Receptor and AMP-activated Protein Kinase Activation in C2C12 Myotubes

BACKGROUND: Previous studies have shown that 17beta-estradiol activates AMP-activated protein kinase (AMPK) in rodent muscle and C2C12 myotubes and that acute 17beta-estradiol treatment rapidly increases AMPK phosphorylation possibly through non-genomic effects but does not stimulate glucose uptake. Here, we investigated whether 24-hour 17beta-estradiol treatment stimulated glucose uptake and regulated the expression of genes associated with glucose and energy metabolism through the genomic effects of estrogen receptor (ER) in C2C12 myotubes. METHODS: C2C12 myotubes were treated with 17beta-estradiol for 24 hours, and activation of AMPK, uptake of glucose, and expression of genes encoding peroxisome proliferator-activated receptor γ coactivator 1α, carnitine palmitoyltransferase 1β, uncoupling protein 2, and glucose transporter 4 were examined. Furthermore, we investigated whether AMPK inhibitor (compound C) or estrogen receptor antagonist (ICI182.780) treatment reversed 17beta-estradiol-induced changes. RESULTS: We found that 24-hour treatment of C2C12 myotubes with 17beta-estradiol stimulated AMPK activation and glucose uptake and regulated the expression of genes associated with glucose and energy metabolism. Treatment of C2C12 myotubes with the estrogen receptor antagonist (ICI182.780) reversed 17beta-estradiol-induced AMPK activation, glucose uptake, and changes in the expression of target genes. Furthermore, treatment with the AMPK inhibitor (compound C) reversed 17beta-estradiol-induced glucose uptake and changes in the expression of target genes. CONCLUSION: Our results suggest that 17beta-estradiol stimulates AMPK activation and glucose uptake and regulates the expression of genes associated with glucose and energy metabolism in C2C12 myotubes through the genomic effects of ER.

Diastolic Dysfunction Induced by a High-Fat Diet Is Associated with Mitochondrial Abnormality and Adenosine Triphosphate Levels in Rats

BACKGROUND: Obesity is well-known as a risk factor for heart failure, including diastolic dysfunction. However, this mechanism in high-fat diet (HFD)-induced obese rats remain controversial. The purpose of this study was to investigate whether cardiac dysfunction develops when rats are fed with a HFD for 10 weeks; additionally, we sought to investigate the association between mitochondrial abnormalities, adenosine triphosphate (ATP) levels and cardiac dysfunction. METHODS: We examined myocardia in Wistar rats after 10 weeks of HFD (45 kcal% fat, n=6) or standard diet (SD, n=6). Echocardiography, histomorphologic analysis, and electron microscopy were performed. The expression levels of mitochondrial oxidative phosphorylation (OXPHOS) subunit genes, peroxisome-proliferator-activated receptor gamma co-activator-1alpha (PGC1alpha) and anti-oxidant enzymes were assessed. Markers of oxidative stress damage, mitochondrial DNA copy number and myocardial ATP level were also examined. RESULTS: After 10 weeks, the body weight of the HFD group (349.6+/-22.7 g) was significantly higher than that of the SD group (286.8+/-14.9 g), and the perigonadal and epicardial fat weights of the HFD group were significantly higher than that of the SD group. Histomorphologic and electron microscopic images were similar between the two groups. However, in the myocardium of the HFD group, the expression levels of OXPHOS subunit NDUFB5 in complex I and PGC1alpha, and the mitochondrial DNA copy number were decreased and the oxidative stress damage marker 8-hydroxydeoxyguanosine was increased, accompanied by reduced ATP levels. CONCLUSION: Diastolic dysfunction was accompanied by the mitochondrial abnormality and reduced ATP levels in the myocardium of 10 weeks-HFD-induced rats.

Increase in the Serum Parathyroid Hormone Level During a Bisphosphonate Drug Holiday

After discontinuation of bisphosphonate therapy, an antiresorptive effect and antifracture protection persist for an undefined period. Patients are encouraged to continue calcium and vitamin D supplementation, during a bisphosphonate drug holiday. However, assessment of adequate calcium intake during the bisphosphonate drug holiday is difficult. Therefore, we measured the serum intact parathyroid hormone (PTH) level as a surrogate marker. A premenopausal woman discontinued bisphosphonate therapy, after 7.5 years of treatment. Two months later, blood calcium and phosphorus levels were normal, serum 25-hydroxyvitamin D level was 31.3 ng/mL, but serum PTH level had increased to 94.9 pg/mL. The elemental calcium supplement dose was increased to 600 mg/day, with no change in the cholecalciferol dose (400 IU). Her serum PTH levels decreased to 49.1 after 4 months and 32.9 pg/mL after 5 months. The serum PTH level may be helpful in assessing adequate calcium intake during a bisphosphonate drug holiday.

2014 Clinical Practice Guidelines for Overweight and Obesity in Korea

The dramatic increase in the prevalence of obesity and its accompanying comorbidities are major health concerns in Korea. Obesity is defined as a body mass index > or =25 kg/m2 in Korea. Current estimates are that 32.8% of adults are obese: 36.1% of men and 29.7% of women. The prevalence of being overweight and obese in national surveys is increasing steadily. Early detection and the proper management of obesity are urgently needed. Weight loss of 5% to 10% is the standard goal. In obese patients, control of cardiovascular risk factors deserves the same emphasis as weight-loss therapy. Since obesity is multifactorial, proper care of obesity requires a coordinated multidisciplinary treatment team, as a single intervention is unlikely to modify the incidence or natural history of obesity.

Effect of 17-beta Estradiol on Adipocyte Lipin-1 Expression in OLETF Rat

No abstract available.

Exendin-4 Protects Oxidative Stress-Induced beta-Cell Apoptosis through Reduced JNK and GSK3beta Activity

Oxidative stress induced by chronic hyperglycemia in type 2 diabetes plays a crucial role in progressive loss of beta-cell mass through beta-cell apoptosis. Glucagon like peptide-1 (GLP-1) has effects on preservation of beta-cell mass and its insulin secretory function. GLP-1 possibly increases islet cell mass through stimulated proliferation from beta-cell and differentiation to beta-cell from progenitor cells. Also, it probably has an antiapoptotic effect on beta-cell, but detailed mechanisms are not proven. Therefore, we examined the protective mechanism of GLP-1 in beta-cell after induction of oxidative stress. The cell apoptosis decreased to ~50% when cells were treated with 100 microM H2O2 for up to 2 hr. After pretreatment of Ex-4, GLP-1 receptor agonist, flow cytometric analysis shows 41.7% reduction of beta-cell apoptosis. This data suggested that pretreatment of Ex-4 protect from oxidative stress-induced apoptosis. Also, Ex-4 treatment decreased GSK3beta activation, JNK phosphorylation and caspase-9, -3 activation and recovered the expression of insulin2 mRNA in beta-cell lines and secretion of insulin in human islet. These results suggest that Ex-4 may protect beta-cell apoptosis by blocking the JNK and GSK3beta mediated apoptotic pathway.

Protective Effects of Glucagon Like Peptide-1 on HIT-T15 beta Cell Apoptosis via ER Stress Induced by 2-deoxy-D-glucose / 당뇨병

BACKGROUND: The characteristic feature of pancreatic beta cells is highly developed endoplasmic reticulum (ER) due to a heavy engagement in insulin secretion. The ER serves several important function, including post-translational modification, folding, and assembly of newly synthesized secretory proteins, and its proper function is essential to cell survival. Various stress conditions can interfere with ER function. Pancreatic beta cells may be particularly vulnerable to ER stress that causes to impair insulin biosynthesis and beta cell survival through apoptosis. Glucagon like peptide-1 (GLP-1) is a new drug for treatment of type 2 diabetes and has effects on stimulation of insulin secretion and beta cell preservation. Also, it may have an antiapoptotic effect on beta cells, but detailed mechanisms are not proven. Therefore, we investigated the protective mechanism of GLP-1 in beta cells through ER stress response induced by 2-deoxy-D-glucose (2DG). METHODS: For induction of the ER stress, HIT-T15 cells (hamster beta cell line) were treated with 2DG (10 mM). Apoptosis was evaluated with MTT assay, hoechst 33342 staining and Annexin/PI flow cytometry. Expression of ER stress-related molecules was determined by real-time PCR or western blot. For blocking ER stress, we pretreated HIT-T15 cells with exendin-4 (Ex-4; GLP-1 receptor agonist) for 1 hour before stress induction. RESULTS: After induction with ER stress (2DG), beta cells were lost by apoptosis. We found that Ex-4 had a protective effect through ER stress related molecules (GRP78, GRP94, XBP-1, eIF2alpha, CHOP) modulation. Also, Ex-4 recovered the expression of insulin2 mRNA in beta cells. CONCLUSION: These results suggest that GLP-1 may protect beta cells apoptosis through ER stress modulation.

The Effects of D-Chiro-Inositol on Glucose Metabolism in 3T3-L1 Cells / 당뇨병

BACKGROUND: The target of the treatment of metabolic syndrome and diabetes is an improvement of insulin resistance. D-chiro-inositol (DCI) plays a role in a phospholipid mediating intracellular insulin action. In the previous studies, the urine level of DCI were decreased in the diabetic animal with insulin resistance. Some clinical studies showed that DCI improved a glucose level and HbA1c. Therefore we studied the relationship between DCI and glucose metabolism, especially insulin resistance. METHODS: To investigate the mechanism of DCI affecting the glucose metabolism, we examined the effects of DCI on 2-deoxyglucose uptake, gene expression of adipocytokines and AMPK pathway by using RT-PCR and western blot in 3T3-L1 cells. RESULTS: Insulin-stimulated 2-deoxyglucose uptake increased in DCI-treated cells by about 1.2-fold (relative to the control) and was inhibited by phosphoinositide 3-kinase (PI3 Kinase) inhibitors (Wortmanin, LY294002) and AMPK inhibitor (STO-609). In Western blot analysis, it didn't show the difference of phosphorylation of Akt and AMPK between DCI-treated group and control in 3T3-L1 cells. However, DCI decreased the gene expression of resistin in 3T3-L1 cells. CONCLUSION: DCI may involve other pathway of insulin signaling, but not PI3 Kinase and AMPK signaling pathways and it may be useful in managing metabolic syndrome by improving insulin resistance through increasing glucose uptake and decreasing resistin relevant to insulin resistance.

Body Mass Index is Associated with USF1 Haplotype in Korean Premenopausal Women

The upstream stimulatory factor 1 (USF1) gene has been shown to play an essential role as the cause of familial combined hyperlipidemia, and there are several association studies on the relationship between USF1 and metabolic disorders. In this study, we analyzed two single nucleotide polymorphisms in USF1 rs2073653 (306A>G) and rs2516840 (1748C>T) between the case (dyslipidemia or obesity) group and the control group in premenopausal females, postmenopausal females, and males among 275 Korean subjects. We observed a statistically significant difference in the GC haplotype between body mass index (BMI) > or =25 kg/m(2) and BMI <25 kg/m(2) groups in premenopausal females ( chi-square=4.23, p=0.04). It seems that the USF1 GC haplotype is associated with BMI in premenopausal Korean females.

Gastrointestinal Stromal Tumors associated with Neurofibromatosis Type I: A Report of Two Cases

Gastrointestinal stromal tumor (GIST) is the most common non-epithelial neoplasm arising in the gastrointestinal tract, but this tumor is rarely seen in association with type 1 neurofibromatosis (NF-1). We report here on two cases of multiple GISTs of the small intestine that occurred in NF-1 patients. We also analyzed the mutations of c-kit exons 9, 11, 13 and 17 and the plateletderived growth factor receptor-alpha (PDGFRA) exons 12 and 18 in two GIST patients. Histologically, the NF-1-associated GISTs were similar to those of non-the NF-1 GISTs, but they characteristically revealed hyperplastic interstitial cells of Cajal around the GISTs. Immunohistochemically, these tumors showed strong co-expressions of CD117 and CD34. The molecular genetic analysis of the GISTs showed that all of the c-kit and PDGFRA exons that were analyzed in the GISTs of the two patients were the wild-type, suggesting a limited role for the c-kit and PDGFRA mutations in the tumorigenesis of NF-1-associated GISTs.

Disinfection Efficacy of an Automated Endoscopic Reprocessing System with Ozonated Water / 감염과화학요법

BACKGROUND: The aim of this study is to evaluate the effectiveness of automated ozonated water endoscopic reprocessing system (AORS). MATERIALS AND METHODS: Thirty cases were collected and randomly assigned to 3 groups according to the disinfection methods (Group A, AORS for 5 minutes; Group B, AORS for 10 minutes; Group C, automated disinfection with superoxidized water for 3 minutes 30 seconds). After disinfection was finished, samples were collected from the tip of scopes (Site 1, S1) and rinsing water through biopsy channel (Site 2, S2). Samples were inoculated in blood agar plate for 48 hrs, and then colony count was evaluated. RESULTS: Culture positive rate of S1 was 0% in all three groups. Culture positive rates of S2 were 70% (7/10), 70% (7/10) and 90% (9/10) in group A, group B and group C, respectively. High culture rate group (> or = 1 CFU/ml rinsing water) was 0% (0/10), 30% (3/10) and 70% (7/10) in group A, group B and group C, respectively. Disinfection efficacy between group A and C showed a significant difference in high culture rate (P<0.05). CONCLUSIONS: AORS for 5min was at least equally effective in endoscopic reprocessing compared with the conventional superoxidized water system.

Disinfection Efficacy of an Automated Endoscopic Reprocessing System with Ozonated Water / 감염과화학요법

BACKGROUND: The aim of this study is to evaluate the effectiveness of automated ozonated water endoscopic reprocessing system (AORS). MATERIALS AND METHODS: Thirty cases were collected and randomly assigned to 3 groups according to the disinfection methods (Group A, AORS for 5 minutes; Group B, AORS for 10 minutes; Group C, automated disinfection with superoxidized water for 3 minutes 30 seconds). After disinfection was finished, samples were collected from the tip of scopes (Site 1, S1) and rinsing water through biopsy channel (Site 2, S2). Samples were inoculated in blood agar plate for 48 hrs, and then colony count was evaluated. RESULTS: Culture positive rate of S1 was 0% in all three groups. Culture positive rates of S2 were 70% (7/10), 70% (7/10) and 90% (9/10) in group A, group B and group C, respectively. High culture rate group (> or = 1 CFU/ml rinsing water) was 0% (0/10), 30% (3/10) and 70% (7/10) in group A, group B and group C, respectively. Disinfection efficacy between group A and C showed a significant difference in high culture rate (P<0.05). CONCLUSIONS: AORS for 5min was at least equally effective in endoscopic reprocessing compared with the conventional superoxidized water system.

Chryseobacterium indologenes Isolated from Clinical Specimens / 대한임상미생물학회지

Chryseobacterium indologenes is a nonfastidious, oxidase-positive, gram-negative rod that does not ferment glucose. It is known to be associated with a variety of clinical infections. We report six cases of C. indologenes isolated from clinical specimens, which were seen at our institution over a 2-year period. These organisms were recovered from blood, pleural fluid, peritoneal fluid, bile, endotracheal aspirate, and sputum. We described clinical characteristics, treatment outcome, microbiological characteristics, and in vitro antibiotic susceptibility test.

Incidence of Coagulase-Negative Staphylococci with Reduced Susceptibilities to Glycopeptides and Comparison of Test Methods / 대한임상미생물학회지

BACKGROUND: We tried to evaluate the incidence and clinical significance of coagulase-negative staphylococci (CoNS) with reduced susceptibilities to glycopeptides. In addition, the ability of disk diffusion and Vitek system to detect CoNS with reduced susceptibilities to glycopeptides were compared with the standard agar dilution method. METHODS: One hundred and nineteen clinical isolates of CoNS were recovered at Samsung Medical Center from June to July 1998 and were examined for their susceptibilities to vancomycin and teicoplanin by disk diffusion method (30-microgram disk), Vitek system with GPS-AA card, and agar dilution for the determination of MICs. The records of all patients, from whom CoNS with decreased susceptibility to glycopeptide was isolated, were reviewed. RESULTS: All CoNS showed uniform susceptibility to vancomycin by all three methods but 11 strains (9.2%) exhibited reduced susceptibilities to teicoplanin (MICs, 16 to 32 microgram/mL). All but suspected colonized strains were nosocomially acquired and were isolated from 7 different wards. None were previously treated with teicoplanin. The concordance rates of disk diffusion method and Vitek system with agar dilution method were 94.1% and 84%, respectively. However, the sensitivity of disk diffusion method and Vitek system were only 50.0% and 62.5%, respectively. CONCLUSIONS: This study demonstrates that CoNS with reduced susceptibilities to glycopeptides is not uncommon and may cause true infections in clinical settings. However, neither disk diffusion method nor Vitek system could differentiate these strains from more susceptible isolates.

A Case of Bacteremic Cholangitis Caused by Flavobacterium odoratum / 감염

Flavobacterium odoratum is an obligately aerobic, gram-negative, non-fermentative rod. It has been infrequently isolated from urine, stool, wound, sputum, and blood specimens, but clinical infections caused by this organism are extremely rare. We report a case of bacteremic cholangitis caused by F. odoratum. The organism was simultaneously isolated in blood and bile from a patient, who had fever, sustained jaundice and abdominal pain with adenocarcinoma of the common bile duct. The isolated organism showed the typical biochemical characteristics. The results of antimicrobial sensitivity test showed resistance to aminoglycosides and cephalosporins but susceptibility to imipenem and trimethoprim-sulfamethoxazole.

Performance Analysis of the Beckman Coulter GEN-S Automated Hematology Analyzer / 대한임상병리학회지

BACKGROUND: The complete blood cell count (CBC) and leukocyte differential counts are useful tools for making a diagnosis, treating and monitoring a disease. This study evaluated the perfor-mance of Beckman-Coulter's new model, the Coulter GEN-S system (Beckman Coulter Corpora-tion, Miami, USA; GEN-S), and compared it with the Sysmex NE-8000 (Sysmex Corporation, Kobe, Japan; NE-8000) and Sysmex R-3000 (Sysmex Corporation, Kobe, Japan; R-3000). METHODS: One hundred and four blood samples and 120 blood samples were randomly chosen for a comparison analysis from various in-patients and healthy persons, who visited Samsung med-ical center, respectively. The GEN-S system was evaluated according to the linearity and how well it compared with the NE-8000 in terms of the CBC, and the efficiency of the leukocyte suspect flags. RESULTS: The GEN-S showed that the determination coefficients (R(2)) of the WBC, RBC, platelet count and hemoglobin level were more than 0.94 (P 0.95 (P < 0.001) when compared with the NE-8000. In addition, the correlations of the leukocyte differential counts for neutrophils, eosinophils, and lymphocytes were good, but those for monocytes and basophils were poor. The sensitivity, specificity and positive predictive value of the leukocyte suspect flags of the GEN-S system were 89%, 73%, and 43%, respectively. CONCLUSIONS: These results demonstrate the comparable performance of the GEN-S system in clinical laboratories. However, a separate microscopic differential count is required due to the low positive predictive value for the leukocyte suspect flags.

A Case of Bone Marrow Involvement of Hepatosplenic gamma delta-Cell Lymphoma / 대한혈액학회지

Hepatosplenic gamma delta-cell lymphoma is a rare histologic type of peripheral T-cell lymphomas, clinically characterized by predominant involvement of liver and spleen, no or little adenopathy, and an often aggressive course. We report a case of bone marrow involvement of hepatosplenicgamma delta-cell lymphoma in a 21- year-old woman who presented with fever, anemia, thrombocytopenia, and hepatosplenomegaly. A lymphoma was found subsequently by bone marrow biopsy and computed tomography scan of the abdomen and pelvis. Immunologic characterization of lymphoma cells in bone marrow revealed positivity for CD2, CD3, and CD16/56, and negativity for CD4, CD5, CD7, CD8, CD34, and terminal deoxynucleotidyl transferase (TdT). Conventional cytogenetic studies revealed the presence of isochromosome 7q. Using the PCR-SSCP technique, monoclonal gene rearrangement of the T-cell receptor gamma chain was demonstrated. Thus, we could make a confirmatory diagnosis as hepatosplenic gamma delta-cell lymphoma.