SCI 발표논문

1. 272011

   제1저자 박소연 · 교신저자 류지곤

   Park SY, Ryu JK, Park JH, Yoon H, Kim JY, Yoon YB, Park JG, Lee SH, Kang SB, Park JW, Oh JH

   Prevalence of gastric and duodenal polyps and risk factors for duodenal neoplasm in korean patients with familial adenomatous polyposis.

   Gut Liver. 2011;5(1):46-51.

   Abstract

   BACKGROUND/AIMS The prevalence of gastric polyps, duodenal adenoma and duodenal cancer has been reported as being high among familial adenomatous polyposis (FAP) patients, but there have been no reports of this association in Korea. This study evaluated the prevalence of gastric and duodenal polyps and risk factors for duodenal neoplasm in FAP patients in Korea.

   METHODS We reviewed both initial and follow-up endoscopic results from FAP patients. We also investigated the treatment modality of duodenal adenomas and analyzed the risk factors of duodenal neoplasms by logistic regression analysis.

   RESULTS A total of 148 patients with FAP underwent esophagogastroduodenoscopy (EGD), and the fi ndings were as follows: gastric polyp 39.9% (fundic gland polyp 25.7% and gastric adenoma 14.2%), duodenal adenoma 15.5%, gastric cancer 2.7%, and duodenal cancer 0.7%. There were two cases of gastric cancer that developed from benign gastric polyps. There were progressions of duodenal adenomatosis during follow-up, and some degree of relapse occurred after endoscopic resection. Patients with gastric polyps showed a correlation with the occurrence of duodenal neoplasm (odds ratio, 2.814; p=0.024).

   CONCLUSIONS In Korean FAP patients, gastric cancer was detected more frequently, but fundic gland polyps, duodenal adenoma and duodenal cancer were detected less frequently than in Western patients. FAP patients with gastric polyps should undergo regular EGD, particularly for the early detection of duodenal neoplasia.

   PubMed IF 4.1 소화기내과
2. 262011

   제1저자 김재현 · 교신저자 박경수

   Kim JH, Oh BJ, Lee HN, Park HS, Park SG, Park KS

   Endothelial colony-forming cell coating of pig islets prevents xenogeneic instant blood-mediated inflammatory reaction.

   Cell Transplant. 2011;20(11-12):1805-15.

   Abstract

   Instant blood-mediated inflammatory reaction (IBMIR) causes rapid islet loss in islet transplantation. Endothelial colony-forming cells (ECFCs) display unique abilities to promote angiogenesis and repair vascular injury compared to those of endothelial cells (ECs), which inhibits the allogeneic and xenogeneic IBMIR. We investigated the coating of pig islets with ex vivo-expanded ECFCs as a strategy to overcome xenogeneic IBMIR. Porcine islets were cocultured with human ECFCs in a specially modified culture medium for 2 days to obtain 70-90% coverage. The coating of pig islets with human ECFCs did not affect the glucose-stimulated insulin secretion capacity or diabetes reversal rate after the transplantation of a marginal islet mass under the kidney capsules of diabetic nude mice compared to that of untreated islets. Uncoated islets, PBS control without islets, and the ECFC-coated islets were examined with an in vitro tubing loop assay using human blood. After 60 min of incubation in human blood, the ECFC-coated islets showed platelet consumption inhibition and low C3a and TAT assay results compared to those of the uncoated islets. Furthermore, there was very little macroscopic or microscopic clotting in the human ECFC-coated pig islets. The protective effect was more prominent compared to that of human EC coating of pig islets in our previous study. We investigated the changes in human-specific MCP-1, IL-8, and tissue factor (TF) levels after the coating of pig islets with human ECFCs or human ECs. The IL-8 levels after coating pig islets with ECFCs were significantly lower than those after coating pig islets with ECs, but there were no significant differences in the MCP-1 or TF levels between the ECFCs and ECs. In conclusion, the coating of pig islets with ECFCs completely prevented all components of xenogeneic IBMIR. ECFCs may be a better source of protection against xenogeneic IBMIR than are mature ECs.

   PubMed IF 3.7 내분비대사내과
3. 252011

   제1저자 진종화, 권유욱 · 교신저자 김효수

   Jin J, Kwon YW, Paek JS, Cho HJ, Yu J, Lee JY, Chu IS, Park IH, Park YB, Kim HS, Kim Y

   Analysis of differential proteomes of induced pluripotent stem cells by protein-based reprogramming of fibroblasts.

   J Proteome Res. 2011;10(3):977-89.

   Abstract

   The recent generation of induced pluripotent stem (iPS) cells represents a novel opportunity to complement embryonic stem (ES) cell-based approaches. iPS cells can be generated by viral transduction of specific transcription factors, but there is a potential risk of tumorigenicity by random retroviral integration. We have generated novel iPS (sFB-protein-iPS) cells from murine dermal fibroblasts (FVB-sFB) that have ES cell characteristics, using ES cell-derived cell extracts instead of performing viral transduction. Notably, only cell extracts from an ES cell line (C57-mES) on the C57/BL6 background generated iPS cells in our protocol-not an ES cell line (E14-mES) on the 129 background. Hypothesizing that determining the differences in these 2 mES cell lines will provide vital insight into the reprogramming machinery, we performed proteomic and global gene expression analysis by iTRAQ and mRNA microarray, respectively. We observed that pluripotent ES cells and ES cell extract-derived iPS cells had differential proteomes and global gene expression patterns. Notably, reprogramming-competent C57-mES cells highly expressed proteins that regulate protein synthesis and metabolism, compared with reprogramming-incompetent 129-mES cells, suggesting that there is a threshold that protein synthetic machinery must exceed to initiate reprogramming.

   PubMed IF 3.8 순환기내과
4. 242011

   제1저자 김학령 · 교신저자 정고은

   Kim HL, Chung GE, Park IY, Choi JM, Hwang SM, Lee JH, Kim D

   Elevated peripheral blood monocyte fraction in nonalcoholic fatty liver disease.

   Tohoku J Exp Med. 2011;223(3):227-33.

   Abstract

   An elevated white blood cell (WBC) count is associated with nonalcoholic fatty liver disease (NAFLD); however, a leukocyte subtype that is involved in the pathogenesis of NAFLD is not known. This study was conducted to investigate the association between NAFLD and WBC subtype fractions (%) among healthy elderly Koreans. A total of 794 subjects who underwent a health check-up were investigated. After excluding excessive alcohol intake and other liver diseases, NAFLD was diagnosed based on sonographic findings: hyperechogenecity of liver tissue, difference of echogenicity between liver and kidney, and visibility of vascular structures. The prevalence of NAFLD among entire cohort was 39.0% (310/794). The presence of NAFLD was significantly associated with higher blood WBC counts (5,485 ± 1073 vs. 5,230 ± 995 per mm(3), p = 0.001) and monocyte fraction (6.08 ± 2.40% vs. 5.12 ± 1.31%, p < 0.001). The multiple logistic regression analysis, after controlling confounders, including age, gender, body mass index, systolic and diastolic blood pressure, fasting blood glucose, alanine aminotransferase, triglyceride, and high-density lipoprotein cholesterol, showed that the prevalence risk of NAFLD was increased significantly according to the monocyte fraction quartiles: odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD were 1.00, 2.75 (1.63-4.62), 2.84 (1.67-4.84) and 5.17 (3.03-8.83), respectively. There were no significant associations between NAFLD and the total WBC count quartiles in this model. These results indicate that the elevated peripheral blood monocyte fraction is associated with NAFLD. The monocyte fraction might be a useful marker for NAFLD.

   PubMed IF 1.5 순환기내과
5. 232011

   제1저자 류현정 · 교신저자 송영욱

   Ryu HJ, Takeuchi F, Kuwata S, Kim YJ, Lee EY, Lee EB, Song YW

   The diagnostic utilities of anti-agalactosyl IgG antibodies, anti-cyclic citrullinated peptide antibodies, and rheumatoid factors in rheumatoid arthritis.

   Rheumatol Int. 2011;31(3):315-9.

   Abstract

   The purpose of this study was to investigate the diagnostic utilities of anti-agalactosyl IgG antibody (CARF), anti-cyclic citrullinated peptide (CCP) antibody and rheumatoid factor (RF) in rheumatoid arthritis (RA), non-RA rheumatic diseases, and chronic viral hepatitis. The authors determined serum levels of CARF and anti-CCP2 by ELISA and IgM-RF by a immunonephelometric method in 834 controls and in 397 patients with the following conditions: RA (100), non-RA rheumatic diseases [systemic lupus erythematosus (SLE) 30, primary Sjogren's syndrome 18, systemic sclerosis 30, inflammatory myositis 19], chronic viral hepatitis B and C (HBV 100, HCV 100). The sensitivities of CARF (83%) and anti-CCP (85%) were significantly higher than that of RF (75%, p = 0.01, respectively) in RA, and the specificity of anti-CCP (98%) was significantly higher than those of CARF (92%) and RF (90%, p < 0.001, respectively). A comparison of receiver operating characteristic (ROC) curves revealed that the diagnostic accuracies of CARF and anti-CCP were superior to that of RF (CARF vs. RF, p = 0.008, anti-CCP vs. RF, p = 0.017) in RA. CARF positivity was significantly higher than those of anti-CCP (p = 0.007) and RF (p = 0.008) in systemic sclerosis, and the positivity of CARF was significantly higher than that of anti-CCP in Sjogren's syndrome (p = 0.016). Furthermore, CARF had significantly higher positivity than anti-CCP or RF in chronic viral hepatitis B and C. Finally, the titers of these three markers in RA were significantly higher than in non-RA rheumatic diseases and in chronic viral hepatitis B and C. Our results suggest that anti-CCP is the most useful serologic marker for the differentiation of RA and non-RA rheumatic diseases, and chronic viral hepatitis B and C.

   PubMed IF 3.5 류마티스내과
6. 222011

   제1저자 박경우 · 교신저자 김효수

   Park KW, Park JJ, Jeon KH, Kang SH, Oh IY, Yang HM, Cho HJ, Lee HY, Kang HJ, Koo BK, Oh BH, Park YB, Kim HS

   Enhanced clopidogrel responsiveness in smokers: smokers' paradox is dependent on cytochrome P450 CYP1A2 status.

   Arterioscler Thromb Vasc Biol. 2011;31(3):665-71.

   Abstract

   OBJECTIVE Observational studies have reported enhanced response to clopidogrel in smokers (the smokers' paradox). We examined whether genetic variations in the cytochrome and drug transporter system are associated with the effect of smoking on clopidogrel response.

   METHODS AND RESULTS Clopidogrel on-treatment platelet reactivity (OPR) was measured in 1431 consecutive patients who underwent coronary angiography. Gene samples were available and genotyping was successful in 1123 patients. Nine candidate single-nucleotide polymorphisms in 5 cytochrome genes and 1 drug transporter gene were assessed. The mean OPR of the entire population was 241.9 ± 79.3 (P2Y(12) reaction units). Two hundred forty-nine (17%) smokers had lower OPR compared with 1182 (83%) nonsmokers (227.6 ± 76.0 versus 244.9 ± 79.7, P=0.001). Among the 9 single-nucleotide polymorphisms, only CYP1A2 showed a genotype-dependent change in the effect of smoking on OPR. After adjustment for possible confounding factors, cigarette smoking was associated with a lower OPR by -19 P2Y(12) reaction units (P=0.009) and lower risk for high OPR (odds ratio [OR], 0.48; 95% CI, 0.31 to 0.74) in the AA and CA genotypes but not in the CC genotype.

   CONCLUSIONS Enhanced clopidogrel response in smokers, known as the smokers' paradox, is not universal but was observed only in cytochrome P450 CYP1A2 (-163C>A) A-allele carriers, suggesting a genotype-dependent effect of smoking on clopidogrel responsiveness.

   PubMed IF 8.8 순환기내과
7. 212011

   제1저자 김낙현 · 교신저자 박완범

   Kim NH, Kim M, Lee S, Yun NR, Kim KH, Park SW, Kim HB, Kim NJ, Kim EC, Park WB, Oh MD

   Effect of routine sterile gloving on contamination rates in blood culture: a cluster randomized trial.

   Ann Intern Med. 2011;154(3):145-51.

   Abstract

   BACKGROUND Blood culture contamination leads to inappropriate or unnecessary antibiotic use. However, practical guidelines are inconsistent about the routine use of sterile gloving in collection of blood for culture.

   OBJECTIVE To determine whether the routine use of sterile gloving before venipuncture reduces blood culture contamination rates.

   DESIGN Cluster randomized, assessor-blinded, crossover trial (ClinicalTrials.gov registration number: NCT00973063).

   SETTING Single-center trial involving medical wards and the intensive care unit.

   PARTICIPANTS 64 interns in charge of collection of blood for culture were randomly assigned to routine-to-optional or optional-to-routine sterile gloving groups for 1854 adult patients who needed blood cultures.

   INTERVENTION During routine sterile gloving, the interns wore sterile gloves every time before venipuncture, but during optional sterile gloving, sterile gloves were worn only if needed.

   MEASUREMENTS Isolates from single positive blood cultures were classified as likely contaminant, possible contaminant, or true pathogen. Contamination rates were compared by using generalized mixed models.

   RESULTS A total of 10 520 blood cultures were analyzed: 5265 from the routine sterile gloving period and 5255 from the optional sterile gloving period. When possible contaminants were included, the contamination rate was 0.6% in routine sterile gloving and 1.1% in optional sterile gloving (adjusted odds ratio, 0.57 [95% CI, 0.37 to 0.87]; P = 0.009). When only likely contaminants were included, the contamination rate was 0.5% in routine sterile gloving and 0.9% in optional sterile gloving (adjusted odds ratio, 0.51 [CI, 0.31 to 0.83]; P = 0.007).

   LIMITATION Blood cultures from the emergency department, surgical wards, and pediatric wards were not assessed.

   CONCLUSION Routine sterile gloving before venipuncture may reduce blood culture contamination.

   PubMed IF 17.2 감염내과
8. 202011

   제1저자 Jang JH · 교신저자 정숙향

   Jang JH, Kim JW, Jeong SH, Myung HJ, Kim HS, Park YS, Lee SH, Hwang JH, Kim N, Lee DH

   Clevudine for chronic hepatitis B: antiviral response, predictors of response, and development of myopathy.

   J Viral Hepat. 2011;18(2):84-90.

   Abstract

   Clevudine has been approved for the treatment of chronic hepatitis B (CHB) in South Korea. However, its long-term antiviral effect and safety awaits more study. The aim of this study was to evaluate antiviral efficacy, predictors of virologic response, and development of myopathy after clevudine therapy for CHB. The study included 102 nucleoside naïve CHB patients who had received clevudine for more than 6 months with good compliance. The median duration of clevudine treatment was 53 weeks (range, 25-90 weeks). A retrospective analysis of data retrieved from medical records was performed. The cumulative rate of virologic response [hepatitis B virus (HBV) DNA level <2000 copies/mL] at 48 weeks of clevudine therapy was 81%, and cumulative rate of clevudine resistance was 11% at 60 weeks of treatment. Independent predictors of virologic response to clevudine therapy were hepatitis B e antigen (HBeAg) negativity and rapid decrease of viral load during the early phase of treatment. The clevudine-related myopathy developed in 3.9% of patients, and was reversible after discontinuation of clevudine. Clevudine showed a potent antiviral response, and its effect was higher in HBeAg-negative patients, with rapid viral load reduction after therapy. However, long-term therapy for more than 1 year resulted in the development of considerable resistance and myopathy. Therefore, we should consider alternative antiviral agents if clevudine resistance or clevudine-induced myopathy is developed in patients on clevudine for the treatment of CHB.

   PubMed IF 2.3 소화기내과
9. 192011

   제1저자 이상민 · 교신저자 이세원

   Lee SM, Ahn JS, Noh CS, Lee SW

   Prevalence of allergic diseases and risk factors of wheezing in Korean military personnel.

   J Korean Med Sci. 2011;26(2):201-6.

   Abstract

   The objective of this study was to evaluate the prevalence of asthma, allergic rhinitis, and atopic dermatitis, as well as the risk factors of wheezing among young adults in the Korean military. Young military conscripts in five areas completed a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. For subjects with current wheeze in one sample area, baseline spirometry and bronchodilator response were measured. For subjects without a significant response to bronchodilator (improvement in FEV1 of more than 200 mL and 12%), methacholine challenge tests (MCT) were also performed. Of 3,359 subjects that completed the questionnaire, 354 (10.5%) had current wheeze, 471 (14.0%) had current allergic rhinitis, and 326 (9.7%) had current eczema. Current wheeze was associated with family history of allergic disease, overweight, current smoking, allergic rhinitis, and atopic dermatitis. Of 36 subjects with current wheeze who underwent PFT with or without MCT in the Anyang area, 24 (66.7%) were confirmed to have current asthma. In conclusion, the prevalence of allergic disease in young adults of Korean military is not low, and the risk factors of wheezing include family history of allergic disease, overweight, current smoking, allergic rhinitis, and atopic dermatitis.

   PubMed IF 3.2 호흡기내과
10. 182011

    제1저자 박상원 · 교신저자 이창섭

    Park SW, Lee JH, Kim ES, Kwak YG, Moon CS, Yeom JS, Lee JH, Lee CS

    Adverse events associated with the 2009 H1N1 influenza vaccination and the vaccination coverage rate in health care workers.

    Am J Infect Control. 2011;39(1):69-71.

    Abstract

    We prospectively examined the 2009 H1N1 influenza vaccination coverage rate and the adverse events related to the monovalent vaccine in Korean health care workers. The H1N1 vaccination coverage rate was 91.7%. There were no significant adverse events discouraging the vaccination.

    PubMed IF 2.6 감염내과
11. 172011

    제1저자 김진수 · 교신저자 김태유

    Kim JS, Kim MA, Oh DY, Lee SH, Kim DW, Im SA, Kim WH, Yang HK, Heo DS, Bang YJ, Lee KU, Kim TY, Kim TM, Kim NK, Choe KJ

    Increasing nodal ratio is a poor prognostic factor for survival in stage III-IV (M0) gastric cancer patients who received curative surgery followed by adjuvant chemotherapy: a retrospective study.

    Jpn J Clin Oncol. 2011;41(2):245-52.

    Abstract

    OBJECTIVE The aim of this study is to evaluate the efficacy of adjuvant chemotherapy with 5-fluorouracil and cisplatin in gastric cancer patients and to assess prognostic factors affecting relapse and survival.

    METHODS We retrospectively reviewed the data of 153 patients with Stage III-IV (M0) gastric cancer. The patients were given adjuvant 5-fluorouracil/cisplatin chemotherapy after curative gastric resection with D2 dissection from November 1995 to November 2003. Chemotherapy consisted of cisplatin (60 mg/m(2) as 15 min i.v. infusion) and 5-fluorouracil (1200 mg/m(2) as 12 h continuous i.v. infusion for 4 days) in every 21 days up to six cycles.

    RESULTS During a median follow-up period of 72.9 months (range: 2.0-135.0 months), a total of 105 patients relapsed (locoregional 19.0% vs. systemic 81.0%). The median disease-free survival and overall survival were 19.8 and 32.2 months, respectively. Univariate analysis revealed T stage, TNM stage and lymph node ratio as prognostic factors for survival (P = 0.002, <0.0001 and <0.0001, respectively). After stepwise selection of the factors, multivariate analysis confirmed the impact of the lymph node ratio and T stage on overall survival and disease-free survival.

    CONCLUSIONS In patients with Stage III-IV (M0) gastric cancer, adjuvant 5-fluorouracil/cisplatin chemotherapy was tolerable, but did not seem to confer survival advantage. And the lymph node ratio was found as an independent prognostic factor in this population. This evidence suggests that the clinical trial using more active chemotherapeutic agents is mandatory.

    PubMed IF 2.5 혈액종양내과
12. 162011

    제1저자 김진욱 · 교신저자 김진욱

    Kim JW, Lee SH, Park YS, Hwang JH, Jeong SH, Kim N, Lee DH

    Replicative activity of hepatitis B virus is negatively associated with methylation of covalently closed circular DNA in advanced hepatitis B virus infection.

    Intervirology. 2011;54(6):316-25.

    Abstract

    OBJECTIVES The aim of this study was to examine the methylation status of intrahepatic hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and to elucidate the possible relationship between the cccDNA methylation and viral replicative activity in patients with HBV-related liver cirrhosis (HBV-LC).

    METHODS The methylation status of HBV cccDNA was investigated by bisulfite sequencing in nonneoplastic tissues from 12 patients with HBV-LC who underwent surgical resection for combined hepatocellular carcinoma. Clinical, biochemical and virologic factors were evaluated with respect to the degrees of cccDNA methylation. We also examined the effect of methylation of cccDNA on viral transcription by an in vitro transcription assay.

    RESULTS Variable degrees of CpG methylation were present in the HBV cccDNA from patients with HBV-LC. Old age, low serum HBV DNA levels and low virion productivity were significantly associated with elevated cccDNA methylation. Virion productivity of cccDNA was also lower in HepAD38 cells with a higher degree of cccDNA methylation. In vitro transcription assays showed that the transcriptional activity of HBV cccDNA was suppressed by increased methylation of cccDNA.

    CONCLUSIONS Increased CpG methylation of cccDNA is associated with old age, low serum HBV DNA levels and suppressed replicative activity in HBV-LC.

    PubMed IF 1.8 소화기내과
13. 152011

    제1저자 김덕겸 · 교신저자 Edwin K Silverman

    Kim DK, Hersh CP, Washko GR, Hokanson JE, Lynch DA, Newell JD, Murphy JR, Crapo JD, Silverman EK, COPD Gene Investigators

    Epidemiology, radiology, and genetics of nicotine dependence in COPD.

    Respir Res. 2011;12(1):9.

    Abstract

    BACKGROUND Cigarette smoking is the principal environmental risk factor for developing COPD, and nicotine dependence strongly influences smoking behavior. This study was performed to elucidate the relationship between nicotine dependence, genetic susceptibility to nicotine dependence, and volumetric CT findings in smokers.

    METHODS Current smokers with COPD (GOLD stage ≥ 2) or normal spirometry were analyzed from the COPDGene Study, a prospective observational study. Nicotine dependence was determined by the Fagerstrom test for nicotine dependence (FTND). Volumetric CT acquisitions measuring the percent of emphysema on inspiratory CT (% of lung <-950 HU) and gas trapping on expiratory CT (% of lung <-856 HU) were obtained. Genotypes for two SNPs in the CHRNA3/5 region (rs8034191, rs1051730) previously associated with nicotine dependence and COPD were analyzed for association to COPD and nicotine dependence phenotypes.

    RESULTS Among 842 currently smoking subjects (335 COPD cases and 507 controls), 329 subjects (39.1%) showed high nicotine dependence. Subjects with high nicotine dependence had greater cumulative and current amounts of smoking. However, emphysema severity was negatively correlated with the FTND score in controls (ρ = -0.19, p < .0001) as well as in COPD cases (ρ = -0.18, p = 0.0008). Lower FTND score, male gender, lower body mass index, and lower FEV1 were independent risk factors for emphysema severity in COPD cases. Both CHRNA3/5 SNPs were associated with FTND in current smokers. An association of genetic variants in CHRNA3/5 with severity of emphysema was only found in former smokers, but not in current smokers.

    CONCLUSIONS Nicotine dependence was a negative predictor for emphysema on CT in COPD and control smokers. Increased inflammation in more highly addicted current smokers could influence the CT lung density distribution, which may influence genetic association studies of emphysema phenotypes.

    PubMed IF 5.7 호흡기내과
14. 142011

    제1저자 이지영 · 교신저자 김태유

    Rhee J, Han SW, Cha Y, Ham HS, Kim HP, Oh DY, Im SA, Park JW, Ro J, Lee KS, Park IH, Im YH, Bang YJ, Kim TY

    High serum TGF-α predicts poor response to lapatinib and capecitabine in HER2-positive breast cancer.

    Breast Cancer Res Treat. 2011;125(1):107-14.

    Abstract

    Lapatinib and capecitabine combination therapy is effective in trastuzumab-resistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the biomarkers from serum of patients receiving lapatinib and capecitabine Patients received lapatinib 1,250 mg once daily and capecitabine 2,000 mg/m(2)/day, day 1-14, every 3 weeks. Serum samples were obtained before treatment initiation. Levels of transforming growth factor-α (TGF-α), epidermal growth factor (EGF), extracellular domains of EGFR and HER2 were measured by enzyme-linked immunosorbent assay. The effect of TGF-α on in vitro sensitivity of SK-BR-3 cells to lapatinib was investigated. Sixty-four patients were included. Response rate was significantly higher in patients with low serum TGF-α (≤ 3.75 pg/ml) compared to high TGF-α (>3.75 pg/ml) [61.1% (11/18) vs. 17.4% (8/46), respectively; P = 0.001]. Low serum TGF-α was independently associated with better response in multivariate analysis [adjusted odds ratio, 8.96; 95% confidence interval (CI) 2.4-34.2]. Time-to-progression tended to be shorter in patients with high serum TGF-α compared to low TGF-α [median 3.8 months (95% CI 2.3-5.4) vs. 6.5 (95% CI 6.1-6.8), respectively; P = 0.067]. We confirmed that TGF-α diminished the sensitivity of SK-BR3-cells to lapatinib in vitro. The in vitro antiproliferative effect of cetuximab in combination with lapatinib was higher than that of lapatinib alone in SK-BR3-cells exposed to TGF-α. These data suggest that TGF-α plays a role in resistance to lapatinib and capecitabine therapy among HER2-positive breast cancer.

    PubMed IF 3.3 혈액종양내과
15. 132011

    제1저자 박지아 · 교신저자 이은봉

    Park JA, Pak JJ, Kim J, Lee EY, Lee YJ, Song YW, Lee EB

    Adenosine A2A receptor polymorphisms in Korean patients with systemic sclerosis.

    Int J Immunopathol Pharmacol. 2011;24(2):505-8.

    Abstract

    Adenosine A2A receptor (ADORA2A) regulates inflammation, promotes tissue repair and collagen production by human dermal fibroblasts. We investigated the genetic polymorphisms of ADORA2A in susceptibility to systemic sclerosis (SSc). We genotyped 142 Korean SSc patients and 150 controls for polymorphisms of -1751A/C (rs5996696) and 1976C/T (rs5751876), to cover the promoter and all exon sequences of ADORA2A in Koreans, using TaqMan fluorogenic 5' nuclease assay and single base primer extension assay. Neither -1751A/C nor 1976C/T polymorphism showed difference in the distribution of alleles or genotypes between patients and controls with allele frequency of 89.9% v 91.0% for -1751A (p=0.64) and 56.5% v 54.0% for 1976C (p=0.55). Our findings suggest that the role of ADORA2A in SSc may not be genetically related.

    PubMed IF 2.8 류마티스내과
16. 122011

    제1저자 진호준 · 교신저자 채동완

    Chin HJ, Oh SW, Goo HS, Oh J, Noh JW, Cho JT, Na KY, Kim S, Chae DW, Members of The PREMIER Group

    Effect of RAAS inhibition on the incidence of cancer and cancer mortality in patients with glomerulonephritis.

    J Korean Med Sci. 2011;26(1):59-66.

    Abstract

    Angiotensin II type 1 receptor blocker (ARB), which is frequently prescribed in patients with glomerulonephritis (GN), is suggested to increase the risk of cancer. We registered 3,288 patients with renal biopsy and analyzed the relationship between the use of renin-angiotensin-aldosterone system (RAAS) blockade and the incidence of cancer or cancer mortality. After renal biopsy, cancer developed in 33 patients with an incidence rate of 1.0% (95% of CI for incidence: 0.7%-1.3%). There was no difference in the cancer incidence among the groups according to the use of angiotensin-converting enzyme inhibitors (ACEI) or ARB: 1.2% in the None (23/1960), 0.7% in the ARB-only (5/748), 0.4% in the ACEI-only (1/247), and 1.2% in the ACEI-ARB (4/333) (P = 0.487) groups. The cancer mortality was 2.1%, 0.4%, 0.0%, and 0.3% in None, ACEI-only, ARB-only, and ACEI-ARB group, respectively (P < 0.001). The risk of cancer mortality in patients with ARB was only 0.124 (0.034-0.445) compared to that of non-users of ARB by Cox's hazard proportional analysis. In conclusion, prescription of ACEI or ARB in patients with GN does not increase cancer incidence and recipients of ARB show rather lower rates of all-cause mortality and cancer mortality.

    PubMed IF 3.2 신장내과
17. 112011

    제1저자 박경우 · 교신저자 최동주

    Park KW, Park JJ, Chae IH, Seo JB, Yang HM, Lee HY, Kang HJ, Cho YS, Yeon TJ, Chung WY, Koo BK, Choi DJ, Oh BH, Park YB, Kim HS

    Clinical characteristics of coronary drug-eluting stent fracture: insights from a two-center des registry.

    J Korean Med Sci. 2011;26(1):53-8.

    Abstract

    Stent fracture (SF) has been implicated as a risk factor for in-stent restenosis, but its incidence and clinical characteristics are not well established. Therefore we investigated the conditions associated with stent fracture and its clinical presentation and outcome. Between 2004 and 2007, consecutive cases of SF were collected from the Seoul National University Hospital. Clinical characteristics and outcome of patients with fractured stents were compared with a ten-fold cohort of age and gender matched controls (n = 236). A total of 4,845 patients received percutaneous coronary intervention and 3,315 patients (68.4%) underwent angiographic follow-up. Twenty-eight fractured stents were observed in 24 patients. The incidence of SF was 0.89% for sirolimus-eluting stents (SES) and 0.09% for paclitaxel-eluting stents. Chronic kidney disease, stent implantation in the right coronary artery (RCA), and SES use were independent predictors of drug-eluting stent fracture by multivariate analysis. SF was significantly associated with binary restenosis (11.4% vs 41.7%, P < 0.001) and increased risk of target lesion revascularization (8.1% vs 33.3%, P = 0.001). Patients with SF but without significant restenosis showed excellent outcome despite only medical treatment. In conclusion, SF is associated with increased rates of restenosis and repeat revascularization. Significant risk factors include chronic kidney disease, RCA intervention, and SES use.

    PubMed IF 3.2 순환기내과
18. 102011

    제1저자 이정훈 · 교신저자 윤정환

    Lee JH, Yoon JH, Lee YJ, Yang JI, Kwak MS, Cho EJ, Jang ES, Yu SJ, Choi DH, Jung EU, Kim HY, Kim BH, Chung GE, Kim YJ, Jang JJ, Kim CY, Lee HS

    Mesalamine-induced B7-H1 expression on hepatic stellate cells attenuates autoimmune liver injury.

    Hepatol Res. 2011;41(1):79-86.

    Abstract

    AIM Hepatic stellate cells (HSCs) have immune regulatory functions. Mesalamine is an effective immune regulatory drug for inflammatory bowel disease. Thus, we hypothesized that mesalamine may also modulate the immune regulatory functions of HSCs. Since B7-H1 plays a crucial role in regulating T-cell apoptosis, we evaluated if mesalamine induces B7-H1 expression on HSCs, and if so, whether mesalamine attenuates autoimmune liver injury in vivo.

    METHODS LX-2 cells, an immortalized human HSC cell line, and human peripheral T-cells were used in this study. B7-H1 expression on LX-2 cells following mesalamine treatment was examined by using flow cytometry. Cell viability was analyzed by MTS assay. Concanavalin-A (ConA) mice hepatitis model was used for in vivo study.

    RESULTS Flow cytometry showed that mesalamine treatment increased the B7-H1-expressing LX-2 cell fraction from 45.4% to 88.2%, of which increment is equivalent to that of positive control (29.9%, interferon γ-treated cells). Human T-cells incubated with LX-2 cells showed significantly less cell viability in the presence of mesalamine than cells without mesalamine treatment (P < 0.001). Histological examination revealed that hepatic necroinflammation was significantly attenuated by mesalamine pretreatment (P = 0.019), although serum levels of aminotransferases were not significantly reduced. During the 24-h period following ConA injection, 1 of 10 mice pretreated with mesalamine and 3 of 10 mice without pretreatment died.

    CONCLUSION These results demonstrate that mesalamine enhances B7-H1 expression on HSCs, and thus, induces T-cell apoptosis and attenuates autoimmune liver injury.

    PubMed IF 3.7 소화기내과
19. 92011

    제1저자 정성수 · 교신저자 박경수

    Chung SS, Ahn BY, Kim M, Kho JH, Jung HS, Park KS

    SUMO modification selectively regulates transcriptional activity of peroxisome-proliferator-activated receptor γ in C2C12 myotubes.

    Biochem J. 2011;433(1):155-61.

    Abstract

    PPAR (peroxisome-proliferator-activated receptor) γ, a nuclear receptor, can be conjugated with SUMO (small ubiquitin-like modifier), which results in the negative regulation of its transcriptional activity. In the present study, we tested whether de-SUMOylation of PPARγ affects the expression of PPARγ target genes in mouse muscle cells and investigated the mechanism by which de-SUMOylation increases PPARγ transcriptional activity. We found that the SUMO-specific protease SENP2 [SUMO1/sentrin/SMT3 (suppressor of mif two 3 homologue 1)-specific peptidase 2] effectively de-SUMOylates PPARγ-SUMO conjugates. Overexpression of SENP2 in C2C12 cells increased the expression of some PPARγ target genes, such as FABP3 (fatty-acid-binding protein 3) and CD36 (fatty acid translocase), both in the absence and presence of rosiglitazone. In contrast, overexpression of SENP2 did not affect the expression of another PPARγ target gene ADRP (adipose differentiation-related protein). De-SUMOylation of PPARγ increased ChIP (chromatin immunoprecipitation) of both a recombinant PPRE (PPAR-response element) and endogenous PPREs of the target genes CD36 and FABP3, but ChIP of the PPRE in the ADRP promoter was not affected by SENP2 overexpression. In conclusion, these results indicate that SENP2 de-SUMOylates PPARγ in myotubes, and de-SUMOylation of PPARγ selectively increases the expression of some PPARγ target genes.

    PubMed IF 3.9 내분비대사내과
20. 82011

    제1저자 홍영식, 홍경섭 · 교신저자 황금숙

    Hong YS, Hong KS, Park MH, Ahn YT, Lee JH, Huh CS, Lee J, Kim IK, Hwang GS, Kim JS

    Metabonomic understanding of probiotic effects in humans with irritable bowel syndrome.

    J Clin Gastroenterol. 2011;45(5):415-25.

    Abstract

    GOALS This study was undertaken to evaluate the effects of probiotics on adult patients with irritable bowel syndrome (IBS) through clinical parameters and H nuclear magnetic resonance (NMR)-based metabonomics.

    BACKGROUND As systematic effect of probiotics on inflammatory bowel disease through metabonomics approach has been extensively studied to date, metabonomic characterization of the probiotics effect on IBS is also needed for better understanding the effect with respect to host metabolic mechanism.

    STUDY Seventy-four IBS patients meeting Rome criteria were randomized to receive probiotics and placebo through a parallel-group, double-blind, randomized, placebo-controlled clinical study. Probiotic fermented milk and placebo were administered 3 times daily for 8 weeks. Improvements of IBS were assessed according to Rome III questionnaires and H NMR metabolic profiling of serum and fecal samples from all participants was used to characterize a significant change in serum and fecal metabolome before and after probiotics.

    RESULTS Fecal counts of the Lactobacilli, but not Bifidobacteria species, which included in the probiotic milk, were increased significantly in feces of IBS patients receiving treatment (P=0.014). NMR data set coupled with multivariate statistical analysis identified intrinsically elevated serum levels of glucose (P=0.0265) and tyrosine (P=0.0016) in IBS patients. These levels normalized to those of healthy individuals in the probiotic administration group, but not the placebo group.

    CONCLUSIONS This metabonomic study suggests that in a subset of IBS patients there exists a potential dysregulation in energy homeostasis (serum glucose) and liver function (serum tyrosine) that may be improved through probiotics supplementation. Moreover, global metabolic profiling highlights the potential of metabonomic approach for assessing bowel diseases or symptoms with respect to host metabolic perturbation.

    PubMed IF 2.7 소화기내과
21. 72011

    제1저자 이정훈 · 교신저자 김윤준

    Lee JH, Chung GE, Yu SJ, Hwang SY, Kim JS, Kim HY, Yoon JH, Lee HS, Yi NJ, Suh KS, Lee KU, Jang JJ, Kim YJ

    Long-term prognosis of combined hepatocellular and cholangiocarcinoma after curative resection comparison with hepatocellular carcinoma and cholangiocarcinoma.

    J Clin Gastroenterol. 2011;45(1):69-75.

    Abstract

    GOAL In this study, we attempted to evaluate the prognosis of combined hepatocellular and cholangiocarcinoma (cHCC-CC) with comparison to hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (CC).

    BACKGROUND The prognosis of cHCC-CC has not been fully elucidated. In this study, we attempted to evaluate the prognosis of cHCC-CC with comparison to HCC and CC.

    STUDY Consecutive patients who underwent curative resection for cHCC-CC at a single tertiary care center in Korea and their age, sex, and Child-Turcotte-Pugh class matched HCC and CC patients were included. We evaluated time-to-recurrence (TTR) and overall survival (OS) of cHCC-CC cases and compared them with HCC and CC patients.

    RESULTS Thirty cHCC-CC, 60 HCC, and 60 CC patients were included. For cHCC-CC group, the median TTR and OS were 5.4 and 18.0 months. After adjustment for confounding factors, the cHCC-CC group had a shorter TTR than did HCC group [relative risk (RR), 2.76; P<0.001] and CC group (RR, 2.00; P=0.013), and a shorter OS than HCC group (RR, 4.70; P<0.001). Compared with the each stage I diseases, cHCC-CC had shorter TTR than HCC (RR, 4.59; P=0.001) and CC (RR, 2.74, P=0.015) and shorter OS than HCC (RR, 9.35; P=0.001).

    CONCLUSIONS The results of this study indicated that cHCC-CC had a significantly poorer prognosis than HCC and CC even after curative resection.

    PubMed IF 2.7 소화기내과
22. 62011

    제1저자 윤호일 · 교신저자 한성희

    Yoon HI, Kim JH, Lee JH, Park S, Lee CT, Hwang JY, Nahm SF, Han S

    Comparison of propofol and the combination of propofol and alfentanil during bronchoscopy: a randomized study.

    Acta Anaesthesiol Scand. 2011;55(1):104-9.

    Abstract

    BACKGROUND propofol is an excellent sedative agent for use in patients undergoing bronchoscopy. The addition of an opioid to propofol can be advantageous because of the antitussive effect of the opioid and the possible improvement in sedation quality. However, it may increase the risk of hypoxaemia. To investigate the effect of the addition of alfentanil to propofol, we performed a prospective study to compare propofol-only sedation with propofol-alfentanil combination sedation in patients undergoing bronchoscopy.

    METHODS patients were randomly assigned either to the propofol-only (group P, n=32) or to the propofol-alfentanil combination group (group PA, n=32). The average peripheral oxygen saturation (SpO(2) ) and the lowest SpO(2) during the sedation were compared. Patient and bronchoscopist satisfaction as well as the degree of coughing were compared using a 100 mm visual analogue scale, where 0 indicated the least and 100 indicated the most satisfied.

    RESULTS group P had the higher average SpO(2) (%) during the procedure than group PA (97.8 ± 1.6 and 96.4 ± 1.1, P<0.01) as well as the lowest SpO(2) (%) (95.4 ± 2.7 and 94.0 ± 2.4, P<0.05). Patient satisfaction (92.2 ± 13.5 and 92.3 ± 18.2), bronchoscopist satisfaction (76.6 ± 18.1 and 72.8 ± 19.1), and degree of cough (73.4 ± 22.7 and 72.2 ± 18.5; group P and group PA, respectively) were not different between the groups.

    CONCLUSIONS the combination of propofol and alfentanil resulted in a greater respiratory depression than propofol alone; furthermore, the addition of an opioid did not improve the quality of sedation. In conclusion, we do not recommend sedation with propofol and alfentanil during bronchoscopy.

    PubMed IF 1.9 호흡기내과
23. 52011

    제1저자 김홍빈 · 교신저자 Hooper DC

    Kim HB, Park CH, Gavin M, Jacoby GA, Hooper DC

    Cold shock induces qnrA expression in Shewanella algae.

    Antimicrob Agents Chemother. 2011;55(1):414-6.

    Abstract

    Plasmid-carried quinolone resistance genes, like qnrA, are widespread in Enterobacteriaceae. To gain insight into its little-understood native functions, we studied the effect of environmental conditions on chromosomal qnrA expression in Shewanella algae. Among conditions of DNA damage, oxidative and osmotic stress, starvation, heat, and cold, only cold shock increased gene expression, as measured by quantitative reverse transcription-PCR (qRT-PCR). Induction was graded and occurred during growth arrest, suggesting that qnrA may contribute to the adaptation of Shewanella to low temperatures.

    PubMed IF 4.2 감염내과
24. 42011

    제1저자 김동완 · 교신저자 허대석

    Kim DW, Lee SH, Lee JS, Lee MA, Kang JH, Kim SY, Shin SW, Kim HK, Heo DS

    A multicenter phase II study to evaluate the efficacy and safety of gefitinib as first-line treatment for Korean patients with advanced pulmonary adenocarcinoma harboring EGFR mutations.

    Lung Cancer. 2011;71(1):65-9.

    Abstract

    This study was designed to prospectively evaluate the efficacy and safety of first-line gefitinib treatment in patients with advanced pulmonary adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations and to explore the molecular factors affecting the efficacy of gefitinib. Tumor tissue, derived from either the original tumor or the metastatic or recurrent site was taken from chemo-naïve pts with advanced (stage IIIB, IV, and recurrent) pulmonary adenocarcinoma. Tumor genomic DNA underwent direct sequencing for EGFR exons 18, 19, 20, and 21. Patients with EGFR mutations received 250 mg of gefitinib daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression free survival (PFS), overall survival (OS) and tolerability. Out of 147 screened patients, 45 pts (31%) had EGFR mutations and received gefitinib. The most common EGFR mutations were in-frame exon 19 deletions (29 pts, 64%) and L858R point mutation in exon 21 (15 pts, 33%). One patient had atypical mutation of L861Q in exon 21. The ORR was 53.3% (95% CI, 38.6-67.9) and disease control rate (DCR) including stable disease was 86.7%. The median progression free survival (PFS) was 398 days and the median overall survival (OS) was 819 days. Treatment was well tolerated. Grade 3/4 adverse events (AEs) were reported by 6 patients and treatment-related Grade 3 AEs by 3 patients. There were no treatment-related Grade 4 AEs. Exploratory subgroup analysis according to the EGFR mutation subtypes was carried out. The ORR and DCR were higher in patients with exon 19 deletions than those with L858R (62.1% vs 33.3%; P=0.0705 and 96.6% vs 66.7%; P=0.0062, respectively). All 4 patients with progressive disease had a L858R mutation. No secondary resistant mutations such as T790M mutation or insertions in exon 20 were found in those patients. In addition, OS was significantly better in patients with exon 19 deletions than those with L858R (24-month OS rate was 72.1% vs 32.0%, P=0.0148). Gefitinib as the first-line treatment for Korean patients with advanced pulmonary adenocarcinoma harboring EGFR mutations was effective and well tolerated. Subgroup analysis suggests that the benefit from gefitinib treatment was more prominent in patients with the exon 19 deletion mutations (ClinicalTrials.gov number, NCT00344773).

    PubMed IF 5.3 혈액종양내과
25. 32011

    제1저자 송은영 · 교신저자 윤정환

    Song EY, Shin Y, Roh EY, Sue S, Park MH, Kim BH, Kim W, Yoon JH, Lee YJ, Park SJ, Jung EU, Lee JH, Myung SJ, Kim YJ, Lee HS

    Serum HBsAg levels during peginterferon α-2a treatment with or without thymosin α-1 in HBeAg-positive chronic hepatitis B patients.

    J Med Virol. 2011;83(1):88-94.

    Abstract

    The importance of serum hepatitis B surface antigen (HBsAg) level as a surrogate marker for viral load and a predictor of treatment response remains unclear. The aim of this study was to investigate whether serum HBsAg correlates with serum hepatitis B virus (HBV) DNA during peginterferon (PEG-IFN) α-2a treatment (with or without thymosin α-1) in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients and whether it can predict treatment response. Sera from 37 HBeAg-positive chronic hepatitis B patients receiving 48-weeks PEG-IFN α-2a with (n = 20) or without (n = 17) an initial 12-weeks thymosin α-1 were obtained at baseline and at weeks 12, 24, 36, 48 (end of treatment), 56, 72, 84, and 96 (end of follow-up). Taqman HBV DNA tests (Roche) and Architect HBsAg QT (Abbott) were performed. There was a moderate correlation between the HBsAg and HBV DNA levels (r = 0.452, P < 0.001). Median HBsAg levels at baseline and at week 96 were 6,218 IU/ml and 4,038 IU/ml, respectively. The mean HBV DNA and alanine aminotransferase (ALT) levels were 7.48 log(10) IU/ml and 173 IU/L at baseline and 5.37 log(10) IU/ml and 102 IU/L at week 96, respectively. A decrease to <60% of baseline levels of HBsAg at week 12 was identified as an independent predictive factor for HBeAg seroconversion (OR = 45.7, P < 0.05) at week 96. Serum HBsAg levels may be helpful for predicting the response to PEG-IFN therapy in HBeAg-positive chronic hepatitis B patients.

    PubMed IF 3.7 소화기내과
26. 22011

    제1저자 이준철 · 교신저자 허대석

    Lee JC, Lee KM, Ahn YO, Suh B, Heo DS

    A possible mechanism of impaired NK cytotoxicity in cancer patients: down-regulation of DAP10 by TGF-beta1.

    Tumori. 2011;97(3):350-7.

    Abstract

    AIMS AND BACKGROUND Elevated TGF-BETA1 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients. However, the molecular mechanism of immunosuppression by TGF-BETA1 is not yet clarified.

    METHODS IL-2-activated human NK cells were cultured with TGF-BETA1. Protein levels of NKG2D and DAP10 were examined by FACS or immunoblot analyses. Real-time RTPCR was performed to quantify the transcription levels. MAPK inhibitors were used to investigate intracellular signaling.

    RESULTS TGF-BETA1 down-regulated total and surface NKG2D, which was partially dependent on transcriptional regulation. TGF-BETA1 treatment of human NK cells resulted in significant changes in both transcriptional and translational levels of DAP10. Moreover, treatment with bafilomycin A1 or folimycin restored total NKG2D levels in TGF-BETA1-treated NK cells. The impaired NKG2D down-modulation by TGF-BETA1 was not associated with activation of the MAPK signaling pathway.

    CONCLUSIONS TGF-BETA1 down-modulates surface NKG2D expression by controlling the transcriptional and translational levels of DAP10.

    PubMed IF 2 혈액종양내과
27. 12011

    제1저자 정은숙 · 교신저자 임춘수

    Jung ES, Kim SM, Cha RH, Oh YK, Kim YS, Kim S, Lim CS

    Impact of polymorphisms of the genes encoding angiotensin II-forming enzymes on the progression of IgA nephropathy.

    Nephron Clin Pract. 2011;118(2):c122-9.

    Abstract

    BACKGROUND/AIMS Angiotensin II has been shown to play an important role in various renal diseases. Genetic polymorphisms of the renin-angiotensin system have been reported to be related to the clinical outcomes in immunoglobulin A nephropathy (IgAN). We investigated the association of polymorphisms of the genes encoding major angiotensin II-forming enzymes with the development and progression of IgAN among Korean patients.

    METHODS A total of 261 IgAN patients and 300 healthy controls were studied. The polymorphisms of angiotensin-converting enzyme gene (I/D, A2350G) and chymase (CMA) gene (rs1800875, rs1800876) were determined.

    RESULTS No significant difference was observed in the genotype and allele frequencies of the polymorphisms between IgAN patients and controls. The frequency of AA/AG genotypes of CMA rs1800875 and CC/CT genotype of CMA rs1800876 were significantly higher in patients with progressive disease course than in those with stable course (53.2 vs. 38.6%, p = 0.029; 89.6 vs. 78.3%, p = 0.031, respectively). In the Cox regression model with adjustment for clinical risk factors, CMA rs1800875 AA/AG genotypes remained an independent risk factor (hazard ratio 2.351; p = 0.001).

    CONCLUSION Our results suggest that the CMA rs1800875 polymorphism is associated with the progression of IgAN in Korean patients.

    PubMed IF 1.606 신장내과

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