SCI 발표논문

1. 1462009

   제1저자 천지용 · 교신저자 김윤준

   Chun JY, Bae JS, Park TJ, Kim JY, Park BL, Cheong HS, Lee HS, Kim YJ, Shin HD

   Putative association of DNA methyltransferase 1 (DNMT1) polymorphisms with clearance of HBV infection.

   BMB Rep. 2009;42(12):834-9.

   Abstract

   DNA methyltransferase (DNMT) 1 is the key enzyme responsible for DNA methylation, which often occurs in CpG islands located near the regulatory regions of genes and affects transcription of specific genes. In this study, we examined the possible association of DNMT1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Seven common polymorphic sites were selected by considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n = 1,100). Statistical analysis demonstrated that two intron polymorphisms of DNMT1, +34542G > C and +38565G > T, showed significant association with HBV clearance in a co-dominant model (OR = 1.30, P(corr) = 0.03) and co- dominant/recessive model (OR = 1.34-1.74, P(corr) = 0.01-0.03), respectively. These results suggest that two intron polymorphisms of DNMT1,+34542G > C and +38565G > T, might affect HBV clearance.

   PubMed IF 4.1 소화기내과
2. 1452009

   제1저자 신동호,채인호 · 교신저자 연태진

   Shin DH, Chae IH, Youn TJ, Cho SI, Kwon DA, Suh JW, Chang HJ, Cho YS, Chung WY, Choi YJ, Gwon HC, Han KR, Choi DJ

   Reasonable duration of Clopidogrel use after drug-eluting stent implantation in Korean patients.

   Am J Cardiol. 2009;104(12):1668-73.

   Abstract

   Current guidelines recommend that clopidogrel be given to patients for 12 months after drug-eluting stent (DES) implantation. However, the evidence is insufficient to support the benefit of long-term clopidogrel therapy, especially in Asian patients. The aim of this study was to evaluate whether different durations of clopidogrel use might influence long-term outcomes after DES implantation. A total of 844 patients from 4 medical centers in Korea who had undergone successful DES implantation from November 2004 to April 2006 were enrolled. Patients who were event free at 6-month follow-up were divided into 2 groups by clopidogrel use (575 users, 163 nonusers) and followed. The end point was a composite of death, myocardial infarction, and stent thrombosis. During 1,056.4 patient-years of follow-up (median 2.02), there were 7 deaths, 3 myocardial infarctions, and 2 episodes of stent thrombosis. No significant differences in the primary end point were observed between clopidogrel users and nonusers (cumulative incidence 2.9% vs 2.8%, p = 0.578; adjusted hazard ratio 0.67, 95% confidence interval 0.16 to 2.77). In analysis with time-dependent covariates, the incidence rates of the primary end point during observation periods with and without clopidogrel were similar, although the effect estimates were broad (9.9 with and 10.6 without clopidogrel per 1,000 patient-years; adjusted hazard ratio 0.52, 95% confidence interval 0.09 to 3.17). Interestingly, the effect estimates from propensity score analyses, although they also had wide confidence intervals, were closer to the null than those from conventional Cox analyses. In conclusion, this cohort of Korean patients failed to show an absolute benefit of long-term clopidogrel therapy after DES implantation. The benefit of clopidogrel use beyond 6 months after DES implantation remains uncertain, and hence the decision to use long-term dual-antiplatelet therapy should be based on the risk factors of each patient.

   PubMed IF 2.5 순환기내과
3. 1442009

   제1저자 김태민 · 교신저자 허대석

   Kim TM, Heo DS

   Extranodal NK / T-cell lymphoma, nasal type: new staging system and treatment strategies.

   Cancer Sci. 2009;100(12):2242-8.

   Abstract

   Extranodal NK/T-cell lymphoma (NTCL) is characterized by clinical heterogeneity based on clinical prognostic factors and survival outcome. NTCL subsets are classified as upper aerodigestive tract (UAT) NTCL or non-UAT NTCL; non-UAT has pathologic similarity to UAT-NTCL but is a clinically distinct subtype. Due to the clinical heterogeneity of NTCL, optimal treatment modalities and prognostic factors have been difficult to determine. Ann Arbor staging for lymphomas and the International Prognostic Index (IPI) have been used to predict prognosis for UAT-NTCL; however, local tumor invasiveness (bony invasion or perforation or invasion of the overlying skin) is the most significant factor for poor outcomes in localized UAT-NTCL. Thus, a new staging system is proposed: limited disease (stage I/II UAT-NTCL without local tumor invasiveness) and extensive disease (stage I/II with local invasiveness or stage III/IV disease of UAT NTCL, and non-UAT NTCL) based on treatment outcomes. NTCL is resistant to anthracycline-based chemotherapy, whereas non-anthracycline combination chemotherapy (such as ifosfamide, methotrexate, etoposide, and prednisolone) has an activity against NTCL as either a front-line or as a second-line treatment. The effectiveness of radiotherapy is evident in limited disease, but questionable in extensive disease.

   PubMed IF 4.9 혈액종양내과
4. 1432009

   제1저자 김민석 · 교신저자 김효수

   Kim MS, Lee CS, Hur J, Cho HJ, Jun SI, Kim TY, Lee SW, Suh JW, Park KW, Lee HY, Kang HJ, Lee DS, Koh GY, Nakagami H, Morishita R, Park YB, Kim HS

   Priming with angiopoietin-1 augments the vasculogenic potential of the peripheral blood stem cells mobilized with granulocyte colony-stimulating factor through a novel Tie2/Ets-1 pathway.

   Circulation. 2009;120(22):2240-50.

   Abstract

   BACKGROUND The low engraftment rate of stem/progenitor cells infused via the intracoronary route to the ischemic myocardium is one of the most important factors limiting the efficacy of cell therapy. We investigated the concept of priming peripheral blood stem cells enriched by granulocyte colony-stimulating factor mobilization and apheresis ((mob)PBSCs) with angiopoietin-1 (Ang1), to enhance the engraftment into the ischemic tissue and neovasculogenic potential.

   METHODS AND RESULTS The expression of Tie2, the Ang1 receptor, was significantly higher in (mob)PBSCs than naïve peripheral blood mononuclear cells (19.2+/-3.0% versus 1.2+/-0.8% versus 1.2+/-0.2%; P<0.001 for (mob)PBSCs from acute myocardial infarction (AMI) patients with granulocyte colony-stimulating factor treatment for 3 days versus peripheral blood mononuclear cells from AMI patients versus peripheral blood mononuclear cells from stable angina patients). After 4 hours of cartilage oligomeric matrix protein (COMP)-Ang1 stimulation, (mob)PBSCs committed to the endothelial lineage with the induction of CD31 and VE-cadherin expression, mediated by Tie2/Ets-1 pathway. Priming of (mob)PBSCs with COMP-Ang1 induced the expression of alpha4beta1 and alpha5beta1 integrins, which are also Ets-1 downstream molecules, leading to enhanced adhesion to endothelial cells or fibronectin. In a rabbit ear ischemia/reperfusion model, priming of (mob)PBSCs with COMP-Ang1 improved first-pass engraftment to the distal vascular bed after intraarterial delivery. In a murine ischemic hind-limb model, intravascular delivery of primed (mob)PBSCs enhanced both engraftment and neovascularization.

   CONCLUSIONS The short-term priming with COMP-Ang1 may be a feasible and promising option to activate (mob)PBSCs by enhancing differentiation and adhesiveness and to improve the efficacy of cell therapy for ischemic diseases.

   PubMed IF 41.3 순환기내과
5. 1422009

   제1저자 신철민 · 교신저자 김나영

   Shin CM, Kim N, Lee HS, Lee HE, Lee SH, Park YS, Hwang JH, Kim JW, Jeong SH, Lee DH, Jung HC, Song IS

   Validation of diagnostic tests for Helicobacter pylori with regard to grade of atrophic gastritis and/or intestinal metaplasia.

   Helicobacter. 2009;14(6):512-9.

   Abstract

   BACKGROUND AND AIMS To evaluate the validity of the biopsy-based tests (histology, culture, and urease test) and serology in detecting current Helicobacter pylori infection against a background of atrophic gastritis (AG) or intestinal metaplasia (IM).

   METHODS Helicobacter pylori infection was diagnosed in 651 subjects, using the predefined gold standard for H. pylori tests. The sensitivity, specificity, and positive and negative predictive values of culture, CLOtest, histology (Giemsa stain), and serology were calculated with regard to the histological grade of AG and IM. The level of serum pepsinogen (PG) I and II was also measured as a marker for the presence of AG.

   RESULTS In the study population (n = 651), sensitivity and specificity, respectively, were as follows: culture, 56.2 and 100%; histology, 93.0 and 94.0%; CLOtest, 80.4 and 96.7%; serology, 96.0 and 67.5%. If the analysis is limited to those without AG or IM (n = 158) or to those younger than 40 years (n = 69), all tests, except for culture, had a sensitivity and specificity >90%. The sensitivity of CLOtest and the specificity of serology markedly decreased with progression of AG and IM, and serology was less specific in the presence of AG, as determined by a PG I/II ratio < or =4.1 (specificity, 83.7% vs 40.7% in PG I/II >4.1 and < or =4.1, respectively).

   CONCLUSIONS Any one of biopsy-based tests or serology was found to be excellent for identifying current H. pylori infection among individuals without AG or IM and/or younger patients (<40 years). However, a combination of at least two tests is necessary in the clinical setting of AG or IM.

   PubMed IF 4.6 소화기내과
6. 1412009

   제1저자 김진현 · 교신저자 송영욱

   Kim J, Lee EY, Koh EM, Cha HS, Yoo B, Lee CK, Lee YJ, Ryu H, Lee KH, Song YW

   Comparative clinical trial of S-adenosylmethionine versus nabumetone for the treatment of knee osteoarthritis: an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV study in Korean patients.

   Clin Ther. 2009;31(12):2860-72.

   Abstract

   BACKGROUND S-adenosylmethionine (SAMe) has antiinflammatory and analgesic effects and has been reported to ameliorate the pain and dysfunction of osteoarthritis (OA). The metabolism of SAMe can be affected by geographic or ethnic factors. However, its efficacy and tolerability versus NSAIDs have not been reported in an Asian population.

   OBJECTIVE This study compared the efficacy and tolerability of SAMe 1200 mg/d and nabumetone 1000 mg/d in Korean patients with knee OA.

   METHODS This study was an 8-week, multicenter, randomized, double-blind, double-dummy, Phase IV clinical trial. Eligible patients were aged >18 years and had knee OA according to the clinical and radiologic criteria of the American College of Rheumatology, with a symptom duration of > or =3 months and with a baseline pain rating of >40 mm on a visual analog scale (VAS) or a pain rating on the VAS that was increased by >10 mm or 20% during the washout period compared with the screening visit. After a washout period of 2 weeks, patients with OA were randomly assigned to receive SAMe 1200 mg/d (400 mg TID) or nabumetone 1000 mg once a day in the evening for 8 weeks. The primary end point was the patient's assessment of pain intensity using a VAS at week 8, and the secondary end points were functional class, patient's global assessment of disease status, physician's global assessment of response to therapy, and the Western Ontario and McMaster Universities (WOMAC) index. Adverse events were assessed based on spontaneous reports by patients during interviews and by laboratory tests.

   RESULTS One hundred thirty-four patients, all Asians, were randomly allocated to 1 of 2 treatment groups: 67 patients (56 women, 11 men; mean [SD] age, 63.9 [8.2] years) received SAMe 400 mg TID, and 67 patients (60 women, 7 men; mean age, 62.1 [8.4] years) received nabumetone 1000 mg once daily for 8 weeks. An analysis of changes in pain intensity between weeks 0 and 8 found that both SAMe and nabumetone effectively reduced pain intensity from baseline in each group (mean [SD] change: SAMe, -13.0 [20.8] mm, P < 0.001; nabumetone, -15.7 [20.9] mm, P < 0.001), and the degree of decrease in pain intensity was not significantly different between groups. Secondary end points showed significant improvements from baseline to 8 weeks in both groups. The patient's global assessment of disease status, physician's global assessment of response to therapy, and WOMAC index scores were not significantly different between the groups. Use of acetaminophen as rescue medication did not differ significantly between the groups during weeks 0 to 4 (SAMe, 88.5% [54/61]; nabumetone, 81.3% [52/64]) or weeks 4 to 8 (SAMe, 79.5% [35/44]; nabumetone, 68.5% [37/54]). No significant differences were observed between the treatments in the proportions of patients with all adverse events (SAMe, 35.8% [24/67]; nabumetone, 31.3% [21/67]), drugrelated clinical or laboratory-determined adverse events (SAMe, 22.4% [15/67]; nabumetone, 25.4% [17/67]), or discontinuations due to any adverse events (SAMe, 13.4% [9/67]; nabumetone, 10.4% [7/67]).

   CONCLUSION This study found no significant differences in pain relief or tolerability between treatment with SAMe or nabumetone over 8 weeks in Korean patients with knee OA.

   PubMed IF 3.7 류마티스내과
7. 1402009

   제1저자 김세훈 · 교신저자 박흥우

   Kim SH, Lee JE, Kim SH, Jee YK, Kim YK, Park HS, Min KU, Park HW, Adverse Drug Reaction Research Group in Korea

   Allelic variants of CD40 and CD40L genes interact to promote antibiotic-induced cutaneous allergic reactions.

   Clin Exp Allergy. 2009;39(12):1852-6.

   Abstract

   BACKGROUND The danger hypothesis provides a new perspective of the mechanisms underlying drug allergy. In this study, we evaluated associations between variations in the genes involved in danger signal pathways and antibiotic-induced cutaneous allergic reactions (AICARs).

   METHODS Two hundred cases with urticaria, angio-oedema, maculopapular rash, and erythema multiforme caused by antibiotics were extracted from the database of the Adverse Drug Reaction Research Group in Korea. All cases were confirmed by an allergy specialist. Causative antibiotics included penicillin, cephalosporin, quinolone, and others (approximately 40 different types). Ten single nucleotide polymorphisms (SNPs) in seven genes (-318C>T, +49A>G, and +6230G>A in CTLA4, IVS+17T>C in CD28, -3479T>G and I170V in CD86, -1C>T in CD40, -3458A>G in CD40LG, -308G>A in TNF, and -31T>C in IL1B) were scored for cases and for healthy subjects without a history of AICARs.

   RESULTS Our analysis failed to reveal differences in the distribution of the 10 SNPs between cases and controls. However, we could find a gene-gene interaction between -1C>T in CD40 and -3458A>G in CD40L using multifactor dimensionality reduction analysis. Subjects with minor alleles of both SNPs showed a significant risk for developing AICARs [P=0.017, odds ratio (OR) (95% confidence interval)=2.93 (1.20-7.97)].

   CONCLUSION Our findings suggest that a genetic interaction between CD40 and CD40L favours the development of AICARs.

   PubMed IF 5 알레르기내과
8. 1392009

   제1저자 정진행 · 교신저자 이춘택

   Chung JH, Choe G, Jheon S, Sung SW, Kim TJ, Lee KW, Lee JH, Lee CT

   Epidermal growth factor receptor mutation and pathologic-radiologic correlation between multiple lung nodules with ground-glass opacity differentiates multicentric origin from intrapulmonary spread.

   J Thorac Oncol. 2009;4(12):1490-5.

   Abstract

   INTRODUCTION No standard guidelines detailing recommendations for the selection and treatment for multiple lung nodules with ground-glass opacity (GGO) have been established. For treatment decision, we analyzed epidermal growth factor receptor (EGFR)/K-ras somatic aberrations and pathologic-radiologic correlation in multiple lung nodules presented as GGO to differentiate multifocal lesions from intrapulmonary spread.

   METHODS Twenty-four patients with multiple lung nodules presented as GGO were identified to investigate somatic mutations of EGFR (exon 18-21) and K-ras (codons 2, 13, and 61). This series included 18 atypical adenomatous hyperplasias (AAH), 15 bronchioloalveolar carcinomas (BAC), and 23 adenocarcinomas (ADC) obtained from 24 patients.

   RESULTS High frequency of discordant EGFR mutations (17 of 24, 70.8%) could discriminate tumor clonality (18 of 24, 75%) of multiple lung neoplastic nodules presented as GGO. EGFR mutations were common in AAH (38.9%), BAC (46.7%), and ADC (39.1%). In case 4, AAH and BAC had different mutational changes, and in case 10, the BAC lesion contains EGFR mutation that is not in the invasive ADC. In case 17, the BAC had more mutational changes than the carcinoma. The pure GGO appearance in the radiologic examination corresponded preinvasive pathologic change.

   CONCLUSIONS This study showed that synchronous BAC and/or ADC can have different EGFR or K-ras mutational profiles suggesting these lesions arise as independent events rather than intrapulmonary spread or systemic metastasis. This has significant implication in staging and treatment. These findings might be a clue to establish guidelines of the multiple neoplastic lung nodules with GGO.

   PubMed IF 23.3 호흡기내과
9. 1382009

   제1저자 양재연 · 교신저자 신찬수

   Yang JY, Jung JY, Cho SW, Choi HJ, Kim SW, Kim SY, Kim HJ, Jang CH, Lee MG, Han J, Shin CS

   Chloride intracellular channel 1 regulates osteoblast differentiation.

   Bone. 2009;45(6):1175-85.

   Abstract

   We have identified chloride intracellular channel 1 (CLIC1) through proteomic approach, which was increased in response to canonical wnt signaling while being almost shut-off by adipogenic treatment in mouse mesenchymal C3H10T1/2 cells. We found that CLIC1 was expressed in mouse (MC3T3-E1), rat (ROS 17/2.8 and UMR-106) or human (MG63 and SaOS2) osteoblastic cell lines as well as primary culture of mouse calvarial cells by RT-PCR or Western blot analysis. The expression level of CLIC1 is increased upon treatment of osteogenic medium, whereas it almost disappeared in adipogenic condition, confirming the proteomic data. The expression of CLIC1 was localized mainly in nuclear membrane and vesiculo-cytoplasmic, the latter of which was colocalized with mitochondria. Retroviral overexpression of CLIC1 did not increase whole-cell current but induces hyperpolarization of mitochondrial membrane potential estimated using the fluorescent dye TMRE. Moreover, overexpression of CLIC1 resulted in increase in osteoblastic differentiation of C3H10T1/2 cells as measured by ALP activities or osteoblastic gene expression (osterix, ALP and osteocalcin), although it did not result in induction of Runx2 transcription activities at mouse osteocalcin (OG2) promoter. Finally, in vitro knock-down of CLIC1 using stable siRNA CLIC1 significantly suppressed osteoblastic differentiation. Taken together, these results suggest that CLIC1 may play a role in the regulation of osteoblastic differentiation from mesenchymal progenitors, although its physiologic role in osteoblasts remains to be determined.

   PubMed IF 3.9 내분비대사내과
10. 1372009

    제1저자 강정묵 · 교신저자 김나영

    Kang JM, Kim N, Kim B, Kim JH, Lee BY, Park JH, Lee MK, Lee HS, Jang IJ, Kim JS, Jung HC, Song IS

    Gastroprotective action of Cochinchina momordica seed extract is mediated by activation of CGRP and inhibition of cPLA(2)/5-LOX pathway.

    Dig Dis Sci. 2009;54(12):2549-60.

    Abstract

    Cochinchina momordica seed extract (SKMS10), which is composed of the major compounds momordica saponins, has been evaluated for its gastroprotective effects in rat models of acute gastric mucosal damage. Ethanol and water immersion restraint stress (WRS) induced gastric damage, including hemorrhages and edema, was significantly attenuated by pretreatment with SK-MS10. In addition, SK-MS10 reduced increases of mucosal myeloperoxidase (MPO), IL-1β, and TNFα levels and the expression of cPLA(2), and 5-LOX induced by ethanol or WRS. SK-MS10 also increased hexosamine, adherent mucus, and the expression of MUC5AC. Furthermore, SK-MS10 enhanced the mucosal expression of the CGRP gene and its serum levels.N(G)-methyl L-arginine (L-NMMA) or capsaicin desensitization reversed the SK-MS10-induced gastroprotection effect. These results suggest that SK-MS10 is a gastroprotective agent against acute gastric mucosal damage by suppressing proinflammatory cytokines, downregulating cPLA(2), 5-LOX, and increasing the synthesis of mucus. Furthermore, CGRP-NO pathway was found to play an important role in these gastroprotective effects of SK-MS10.

    PubMed IF 2.8 소화기내과
11. 1362009

    제1저자 강영애 · 교신저자 임재준

    Kang YA, Lee HW, Kim YW, Han SK, Shim YS, Yim JJ

    Association between the -159C/T CD14 gene polymorphism and tuberculosis in a Korean population.

    FEMS Immunol Med Microbiol. 2009;57(3):229-35.

    Abstract

    The aim of the present study was to confirm the association between the CD14-159C/T polymorphism and tuberculosis in the Korean population and to elucidate the functional basis for this putative association. CD14-159C/T genotypes were determined by PCR - restriction fragment length polymorphism analysis in 274 tuberculosis patients and 422 healthy controls. Recombinant CD14 promoter-luciferase reporter constructs, including the -159T or -159C allele, were transfected into K562 and BEAS-2B cells, and luciferase activities were measured and compared. Levels of serum sCD14 and interferon-gamma secreted by peripheral blood mononuclear cells (PBMCs) were measured using enzyme-linked immunosorbent assay.The frequency of -159TT genotypes was higher in tuberculosis patients than in healthy controls. The promoter activity of the -159T allele was higher than that of the -159C allele. Serum sCD14 levels were higher among tuberculosis patients with -159TT genotypes than among those with -159CC genotypes and interferon-gamma release by PBMCs was decreased in subjects with -159TT genotypes. In conclusion, the -159TT CD14 genotypes were associated with tuberculosis development in Koreans. This association might be a result of the higher promoter activity of the -159T allele, the higher level of sCD14, and the decreased interferon-gamma secretion in subjects with -159TT genotypes.

    PubMed IF 1.972 호흡기내과
12. 1352009

    제1저자 Xiaodong Zhou, 이좋은 · 교신저자 이은봉

    Zhou X, Lee JE, Arnett FC, Xiong M, Park MY, Yoo YK, Shin ES, Reveille JD, Mayes MD, Kim JH, Song R, Choi JY, Park JA, Lee YJ, Lee EY, Song YW, Lee EB

    HLA-DPB1 and DPB2 are genetic loci for systemic sclerosis: a genome-wide association study in Koreans with replication in North Americans.

    Arthritis Rheum. 2009;60(12):3807-14.

    Abstract

    OBJECTIVE To identify systemic sclerosis (SSc) susceptibility loci via a genome-wide association study.

    METHODS A genome-wide association study was performed in 137 patients with SSc and 564 controls from Korea using the Affymetrix Human SNP Array 5.0. After fine-mapping studies, the results were replicated in 1,107 SSc patients and 2,747 controls from a US Caucasian population.

    RESULTS The single-nucleotide polymorphisms (SNPs) (rs3128930, rs7763822, rs7764491, rs3117230, and rs3128965) of HLA-DPB1 and DPB2 on chromosome 6 formed a distinctive peak with log P values for association with SSc susceptibility (P=8.16x10(-13)). Subtyping analysis of HLA-DPB1 showed that DPB1*1301 (P=7.61x10(-8)) and DPB1*0901 (P=2.55x10(-5)) were the subtypes most susceptible to SSc in Korean subjects. In US Caucasians, 2 pairs of SNPs, rs7763822/rs7764491 and rs3117230/rs3128965, showed strong association with SSc patients who had either circulating anti-DNA topoisomerase I (P=7.58x10(-17)/4.84x10(-16)) or anticentromere autoantibodies (P=1.12x10(-3)/3.2x10(-5)), respectively.

    CONCLUSION The results of our genome-wide association study in Korean subjects indicate that the region of HLA-DPB1 and DPB2 contains the loci most susceptible to SSc in a Korean population. The confirmatory studies in US Caucasians indicate that specific SNPs of HLA-DPB1 and/or DPB2 are strongly associated with US Caucasian patients with SSc who are positive for anti-DNA topoisomerase I or anticentromere autoantibodies.

    PubMed IF 6.787 류마티스내과
13. 1342009

    제1저자 김민 · 교신저자 박경수

    Kim M, Ahn BY, Lee JS, Chung SS, Lim S, Park SG, Jung HS, Lee HK, Park KS

    The ginsenoside Rg3 has a stimulatory effect on insulin signaling in L6 myotubes.

    Biochem Biophys Res Commun. 2009;389(1):70-3.

    Abstract

    The ginsenoside Rg3 is known to have a protective effect against hyperglycemia, obesity and diabetes in vivo. In this study, we examined the effect of Rg3 on insulin signaling and glucose uptake in cultured L6 myotubes. Rg3 increased glucose uptake both in the basal and insulin-induced states of L6 myotubes. Consistent with the increase in glucose uptake, Rg3 stimulated the phosphorylation of IRS-1 and Akt. Interestingly, Rg3 dramatically increased IRS-1 protein levels, while the protein level of Akt was not affected. Rg3 regulated IRS-1 expression at the transcriptional level and also increased the level of GLUT4 mRNA. Treatment of ginsam, in which Rg3 is the major compound of ginsenosides, increased the IRS-1 protein levels in OLEFT rats. In addition, we found that this effect of Rg3 on insulin signaling was not mediated by the AMPK pathway. In conclusion, these results suggest that Rg3 improves insulin signaling and glucose uptake primarily by stimulating the expression of IRS-1 and GLUT4.

    PubMed IF 2.5 내분비대사내과
14. 1332009

    제1저자 허은영 · 교신저자 임재준

    Heo EY, Chun EJ, Lee CH, Kim YW, Han SK, Shim YS, Lee HJ, Yim JJ

    Radiographic improvement and its predictors in patients with pulmonary tuberculosis.

    Int J Infect Dis. 2009;13(6):e371-6.

    Abstract

    OBJECTIVES The aim of this study was to analyze changes in the extent of radiographic lesions with treatment in patients with pulmonary tuberculosis (TB) and, further, to identify clinical and radiographic factors related to radiographic response.

    METHODS A prospective cohort study including patients with culture-proven pulmonary TB was performed. The posterior-anterior view films of the chest that had been taken at the time of diagnosis and at 6 months after the initiation of treatment were compared. We expressed the extents of the lesions as percentages involving the parenchyma compared with the remaining normal parenchyma.

    RESULTS Among 135 patients enrolled, three failed to achieve smear conversion of sputa after 6 months of treatment. The extent of radiographic lesions decreased from 22.8% at the time of diagnosis to 10.5% after 6 months of treatment. Through the multiple regression model, we found that increasing age (p=0.034), previous history of TB (p=0.016), presence of cavity (p=0.016) or fibrotic lesion (p=0.009), and multidrug-resistant TB (p=0.002) were significantly associated with a poor radiographic response.

    CONCLUSION Patients with less-prominent radiographic improvement and sustained negative tuberculous cultures of the sputa could be closely observed without ordering unnecessary chest radiographs or mycobacterial cultures as well as prolonging treatment.

    PubMed IF 4.6 호흡기내과
15. 1322009

    제1저자 조선욱 · 교신저자 신찬수

    Cho SW, Sun HJ, Yang JY, Jung JY, An JH, Cho HY, Choi HJ, Kim SW, Kim SY, Kim D, Shin CS

    Transplantation of mesenchymal stem cells overexpressing RANK-Fc or CXCR4 prevents bone loss in ovariectomized mice.

    Mol Ther. 2009;17(11):1979-87.

    Abstract

    Osteoporosis is a systemic skeletal disorder characterized by reduced bone mineral density (BMD) and increased risk of fracture. We studied the effects of transplantation of mesenchymal stem cells (MSCs) overexpressing receptor activator of nuclear factor-kappaB (RANK)-Fc and CXC chemokine receptor-4 (CXCR4) using retrovirus on ovariectomy (OVX)-induced bone loss in mice. Ten-week-old adult female C57BL/6 mice were divided into six groups as follows: Sham-operated mice treated with phosphate-buffered saline (PBS) (Sham-op + PBS); OVX mice intravenously transplanted with syngeneic MSCs overexpressing RANK-Fc-DsRED and CXCR4-GFP (RANK-Fc + CXCR4); RANK-Fc-DsRED and GFP (RANK-Fc + GFP); CXCR4-GFP and DsRED (CXCR4 + RED); DsRED and GFP (RED + GFP); or treated with PBS only (OVX + PBS). Measurement of BMD showed that introduction of RANK-Fc resulted in significant protection against OVX-induced bone loss compared to treatment with PBS (-0.1% versus -6.2%, P < 0.05) at 8 weeks after cell infusion. CXCR4 + RED group also significantly prevented bone loss compared to OVX + PBS group (2.7% versus -6.2%, P < 0.05). Notably, the effect of RANK-Fc + CXCR4 was greater than that of RANK-Fc + GFP (4.4% versus -0.1%, P < 0.05) while it was not significantly different from that in CXCR4 + RFP group (4.4% versus 2.7%, P = 0.055) at 8 weeks. Transplantation of MSCs with control virus (RED + GFP group) also resulted in amelioration of bone loss compared to OVX + PBS group (-1.7% versus -6.2%, P < 0.05). Fluorescence-activated cell sorting (FACS) and real-time quantitative PCR (qPCR) analysis for GFP from bone tissue revealed enhanced cell trafficking to bone by co-overexpression of CXCR4. In conclusion, we have demonstrated that intravenous transplantation of syngeneic MSCs overexpressing CXCR4 could promote increased in vivo cell trafficking to bone in OVX mice, which could in itself protect against bone loss but also enhance the therapeutic effects of RANK-Fc.

    PubMed IF 11.4 내분비대사내과
16. 1312009

    제1저자 권민성,나기영 · 교신저자 권혁무

    Kwon MS, Na KY, Moeckel G, Lee SD, Kwon HM

    Urea promotes TonEBP expression and cellular adaptation in extreme hypertonicity.

    Pflugers Arch. 2009;459(1):183-9.

    Abstract

    The transcriptional activator TonEBP is a central regulator of osmolality in the renal medulla and whole body water homeostasis. In order to understand the regulation of TonEBP in the renal medulla, we examined MDCK cells, a kidney-derived epithelial cell line, under conditions mimicking the renal medulla. Moderate changes in ambient tonicity, which was tolerated without prior adaptation, displayed lasting effects on TonEBP in bidirectional manner-stimulated by hypertonicity and inhibited by hypotonicity. TonEBP expression was further enhanced by extreme hypertonicity observed in the inner medullae of antidiuretic animals. Urea stimulated TonEBP expression and promoted cellular proliferation under the conditions of extreme hypertonicity. On the other hand, the TonEBP activity was negatively modulated under these conditions presumably to temper the highly abundant TonEBP. We conclude that urea is critical to the cellular adaptation to extreme hypertonicity and the high level of TonEBP expression in the inner medulla.

    PubMed IF 3.2 신장내과
17. 1302009

    제1저자 정혜승 · 교신저자 김광원

    Jung HS, Choi SH, Kim SJ, Choi DW, Heo JS, Lee KT, Lee JK, Jang KT, Lee BW, Jee JH, Noh JH, Jeong IK, Yang TY, Oh SH, Ahn YR, Kim YS, No H, Lee MK, Kim KW

    Delayed improvement of insulin secretion after autologous islet transplantation in partially pancreatectomized patients.

    Metabolism. 2009;58(11):1629-35.

    Abstract

    The purpose of this study was to evaluate the effects of autologous islet transplantation (ITx) on glucose homeostasis and insulin secretory function after partial pancreatectomy (Px). Fourteen nondiabetic patients who underwent distal Px and autologous ITx for benign pancreatic tumors were enrolled in the study (Px + ITx group). Fourteen normal glucose-tolerant controls and 6 Px without ITx controls were recruited, and all groups were followed over a 24-month period. They performed the 75-g oral glucose tolerance test and the 1-mg glucagon stimulation test. Hemoglobin A(1c) was measured, and indices of insulin secretion were calculated. In the Px + ITx group, insulin secretion increased after a nadir at 6 months. Glucose tolerance, which had been abruptly impaired immediately after Px, recovered until 6 months and stabilized thereafter. As a result, differences in glucose intolerance emerged between the subjects in the Px group and those in the Px + ITx group at 24 months after Px. Characteristic variables in the better insulin secretory subjects in the Px + ITx group included younger age, less extensive pancreas resection, and a greater number of total islets. In summary, delayed amelioration of glucose intolerance was induced by autologous ITx after partial Px, even with a small number of islets.

    PubMed IF 16.7 내분비대사내과
18. 1292009

    제1저자 최성희 · 교신저자 신찬수

    Choi SH, An JH, Lim S, Koo BK, Park SE, Chang HJ, Choi SI, Park YJ, Park KS, Jang HC, Shin CS

    Lower bone mineral density is associated with higher coronary calcification and coronary plaque burdens by multidetector row coronary computed tomography in pre- and postmenopausal women.

    Clin Endocrinol (Oxf). 2009;71(5):644-51.

    Abstract

    OBJECTIVES There is growing evidence for the association between bone mineral density (BMD) and vascular calcification, which is related to cardiovascular disease. Coronary multidetector row computed tomography (MDCT) is a noninvasive tool developed to evaluate coronary status precisely. We used MDCT to evaluate this association.

    DESIGN AND PATIENTS Eight hundred and fifteen subjects received routine checkups. After excluding subjects with factors affecting bone metabolism and cardiovascular disease, 467 subjects were analysed.

    MEASUREMENTS Coronary calcification was measured with MDCT and BMD was measured with dual X-ray absorptiometry (DXA).

    RESULTS The BMD of the femur and the lumbar spine (L-spine) were negatively associated with the coronary calcium score (CCS) after adjusting for age in women but not in men. This inverse correlation was stronger in women with a longer time since menopause (r = -0.35 at femur, postmenopausal women vs. r = -0.10 at femur, premenopausal women, P < 0.05), and it was stronger at the femur than in the L-spine (r = -0.35 at femur vs. r = -0.16 at L-spine, P < 0.01). The relationship was also stronger in postmenopausal women with osteoporosis and osteopaenia than in women with normal BMD. The lower BMD was associated with higher coronary plaque burdens and multidiseased coronary vessels in both men and women (P < 0.01).

    CONCLUSIONS Increased CCS and subclinical atherosclerosis of plaque burdens as revealed by MDCT was associated with a low BMD in all women, independent of cardiovascular risk factors and age.

    PubMed IF 2.8 내분비대사내과
19. 1282009

    제1저자 고영일 · 교신저자 윤성수

    Koh Y, Park J, Ahn KS, Kim I, Bang SM, Lee JH, Yoon SS, Soon Lee D, Yiul Lee Y, Park S, Kim BK

    Different clinical importance of FLT3 internal tandem duplications in AML according to FAB classification: possible existence of distinct leukemogenesis involving monocyte differentiation pathway.

    Ann Hematol. 2009;88(11):1089-97.

    Abstract

    Impact of FLT3 receptor tyrosine kinase activation via internal tandem duplication (ITD) of the juxtamembrane region on outcome of acute myeloid leukemia (AML) is still controversial. Recent researches reveal a role of FLT3 in monocyte differentiation in hematopoiesis. We analyzed the clinical impact of FLT3 alterations in adult AML patients excluding acute promyelocytic leukemia (APL) who received induction chemotherapy according to morphologic classification. Retrospective review of medical records from three centers in Korea between 1997 and 2007 was performed. Polymerase chain reaction was performed on genomic DNA derived from blood samples of patients before induction chemotherapy for FLT3-ITD detection. We assessed overall survival (OS), first disease-free survival (1-DFS), and response to induction chemotherapy. One hundred eighty-four patients (median age 49.1 years, range 16.0-76.5) with AML excluding APL received induction chemotherapy from three centers. FLT3-ITD was detected in 22 patients. One hundred forty-one patients were below age 60. One hundred seventy-nine patients received induction chemotherapy with cytarabine and idarubicin (AId) regimen. One hundred nineteen patients achieved complete remission (CR) after first induction chemotherapy. FLT3-ITD was not related to achievement of CR. 1-DFS was longer in patients without FLT3-ITD (median 1-DFS 16.5 vs. 8.5 months, p = 0.025). 1-DFS was not different according to FLT3-ITD status in nonmonocyte lineage leukemia (p = 0.355), while 1-DFS was shorter in monocyte lineage leukemia for FLT3-ITD positive patients (20.9 vs. 2.4 months, p < 0.001). FLT3-ITD had no impact on OS except for monocyte lineage, where OS was significantly shorter in FLT3-ITD positive group (39.4 vs. 6.0 months, p = 0.026). Moreover FLT3-ITD was stronger prognostic factors in monocyte lineage AML than risk stratification based on cytogenetics. Status of FLT3-ITD should be analyzed differently in AML patients according to morphologic profile. FLT3-ITD is a predictive and prognostic marker only in monocyte lineage patients. This result suggests an existence of distinct subset of monocyte lineage AML with leukemogenesis involving FLT3 activating pathway.

    PubMed IF 2.3 혈액종양내과
20. 1272009

    제1저자 김용진 · 교신저자 김용진

    Kim YJ, Kwon DA, Kim HK, Park JS, Hahn S, Kim KH, Kim KB, Sohn DW, Ahn H, Oh BH, Park YB

    Determinants of surgical outcome in patients with isolated tricuspid regurgitation.

    Circulation. 2009;120(17):1672-8.

    Abstract

    BACKGROUND We sought to identify preoperative predictors of clinical outcomes after surgery in patients with severe tricuspid regurgitation.

    METHODS AND RESULTS We prospectively enrolled 61 consecutive patients (54 women, aged 57+/-9 years) with isolated severe tricuspid regurgitation undergoing corrective surgery. Twenty-one patients (34%) were in New York Heart Association functional class II, 35 (57%) in class III, and 5 (9%) in class IV. Fifty-seven patients (93%) had previous history of left-sided valve surgery. Preoperative echocardiography revealed pulmonary artery systolic pressure of 41.5+/-8.7 mm Hg, right ventricular (RV) end-diastolic area of 35.1+/-9.0 cm(2), and RV fractional area change of 41.3+/-8.4%. The median follow-up duration after surgery was 32 months (range, 12 to 70). Six of the 61 patients died before discharge; thus, operative mortality was 10%. Three of the 55 patients who survived surgery died during follow-up, and 6 patients required readmission because of cardiovascular problems. Thus, 46 patients (75%) remained event free at the end of follow-up. In the 54 patients who underwent 6-month clinical and echocardiographic follow-up, RV end-diastolic area decreased by 29%, with a corresponding 26% reduction in RV fractional area change. Thirty-three patients (61%) showed improved functional capacity after surgery. On multivariable Cox regression analysis, preoperative hemoglobin level (P<0.001) and RV end-systolic area (P<0.001) emerged as independent determinants of clinical outcomes. On receiver operating characteristic curve analysis, we found that RV end-systolic area <20 cm(2) predicted event-free survival with a sensitivity of 73% and a specificity of 67%, and a hemoglobin level >11.3 g/dL predicted event-free survival with a sensitivity of 73% and a specificity of 83%.

    CONCLUSIONS Timely correction of severe tricuspid regurgitation carries an acceptable risk and improves functional capacity. Surgery should be considered before the development of advanced RV systolic dysfunction and before the development of anemia.

    PubMed IF 41.3 순환기내과
21. 1262009

    제1저자 서재빈 · 교신저자 김효수

    Seo JB, Jeon HK, Park KW, Park JS, Bae JH, Kim SW, Moon KW, Choi JW, Lee SG, Chung WY, Youn TJ, Kim SJ, Kim DI, Kim BO, Hyon MS, Park KS, Cha TJ, Hwang HK, Hur SH, Kim HS

    Efficacies of the new paclitaxel-eluting Coroflex Please stent in percutaneous coronary intervention; comparison of efficacy between Coroflex Please and Taxus (ECO-PLEASANT) trial: study rationale and design.

    Trials. 2009;10:98.

    Abstract

    BACKGROUND Previous randomized trials have showed the superiority of Paclitaxel-eluting stent over bare metal stent in angiographic and clinical outcomes. Coroflex Please stent is a newly developed drug eluting stent using the Coroflex stent platform combined with the drug paclitaxel contained in a polymer coating. PECOPS I trial, one-arm observational study, showed that the clinical and angiographic outcomes of Coroflex Please stent were within the range of those of Taxus, the 1st generation paclitaxel-eluting stent (PES). However, there have been no studies directly comparing the Coroflex Please stent with the Taxus Liberte stent that is the newest version of Taxus. Therefore, prospective, randomized trial is required to demonstrate the non-inferiority of Coroflex Please stent compared with Taxus Liberte stent in a head-to-head manner.

    METHODS In the comparison of Efficacy between COroflex PLEASe ANd Taxus stent(ECO-PLEASANT) trial, approximately 900 patients are being prospectively and randomly assigned to the either type of Coroflex Please stent and Taxus Liberte stent via web-based randomization. The primary endpoint is clinically driven target vessel revascularization at 9 months. The secondary endpoints include major cardiac adverse events, target vessel failure, stent thrombosis and angiographic efficacy endpoints.

    DISCUSSION The ECO-PLEASANT trial is the study not yet performed to directly compare the efficacy and safety of the Coroflex Please versus Taxus Liberte stent. On the basis of this trial, we will be able to find out whether the Coroflex Please stent is non-inferior to Taxus Liberte stent or not.

    TRIAL REGISTRATION ClinicalTrials.gov number, NCT00699543.

    PubMed IF 2.1 순환기내과
22. 1252009

    제1저자 윤원재 · 교신저자 윤용범

    Yoon WJ, Yoon YB, Kim YJ, Ryu JK, Kim YT

    Metastasis to the gallbladder: a single-center experience of 20 cases in South Korea.

    World J Gastroenterol. 2009;15(38):4806-9.

    Abstract

    AIM To evaluate the clinicopathologic characteristics of patients with metastases to the gallbladder (MGBs).

    METHODS We performed a single-center retrospective study of 20 patients with MGBs diagnosed pathologically from 1999 to 2007.

    RESULTS Among 417 gallbladder (GB) malignancies, 20 (4.8%) were MGBs. The primary malignancies originated from the stomach (n = 8), colorectum (n = 3), liver (n = 2), kidney (n = 2), skin (n = 2), extrahepatic bile duct (n = 1), uterine cervix (n = 1), and appendix (n = 1). Twelve patients were diagnosed metachronously, presenting with cholecystitis (n = 4), abdominal pain (n = 2), jaundice (n = 1), weight loss (n = 1), and serum CA 19-9 elevation (n = 1); five patients were asymptomatic. The median survival after the diagnosis of MGB was 8.7 mo. On Cox regression analysis, R0 resection was the only factor associated with a prolonged survival [hazard ratio (HR): 0.01, P = 0.002]; presentation with cholecystitis was associated with poor survival (HR: 463.27, P = 0.006).

    CONCLUSION MGBs accounted for 4.8% of all pathologically diagnosed GB malignancies. The most common origin was the stomach. The median survival of MGB was 8.7 mo.

    PubMed IF 7.7 소화기내과
23. 1242009

    제1저자 최의근 · 교신저자 장혁재

    Choi EK, Chun EJ, Choi SI, Chang SA, Choi SH, Lim S, Rivera JJ, Nasir K, Blumenthal RS, Jang HC, Chang HJ

    Assessment of subclinical coronary atherosclerosis in asymptomatic patients with type 2 diabetes mellitus with single photon emission computed tomography and coronary computed tomography angiography.

    Am J Cardiol. 2009;104(7):890-6.

    Abstract

    We evaluated the characteristics of coronary artery disease in asymptomatic patients with type 2 diabetes mellitus (DM) using single photon emission computed tomography (SPECT) and coronary computed tomographic angiography (CCTA). A total of 116 patients with DM without abnormal electrocardiographic findings or evidence of peripheral arterial disease (number of risk factors > or =2; 62 +/- 7 years, 59% men) underwent CCTA and SPECT. Of the 116 patients with DM, 88 (76%) had a normal single photon emission computed tomographic findings, and 28 (24%) had abnormal perfusion defects. Of the 116 patients, 92 (79%) had atherosclerotic plaques (2 +/- 2 segments per subject), and 20 (17%) had significant stenosis seen on CCTA. Patients with DM and normal findings on SPECT had a similar prevalence of atherosclerotic plaque (78% vs 82%), significant stenosis (15% vs 25%), severe stenosis (7% vs 7%), and calcified (40% vs 43%), mixed (49% vs 57%), and noncalcified plaques (26% vs 29%) and a high (>100) coronary artery calcium score (32% vs 29%; all p >0.05) compared to those with abnormal findings on SPECT. During the mid-term follow-up (24 +/- 4 months), 5 cardiac events occurred in patients with DM and normal findings on SPECT, only in those with occult CAD on CCTA: 1 sudden cardiac death and 4 revascularization procedures. In conclusion, a significant percentage of patients with DM and normal eletrocardiographic findings, no peripheral arterial disease, and normal findings on SPECT have evidence of occult CAD on CCTA. Furthermore, a small percentage had had a cardiac event by mid-term follow-up. SPECT showed limited capability to differentiate the coronary risks between patients with DM and no coronary plaque and from those with a certain degree of disease; 2 circumstances that represent different coronary risks.

    PubMed IF 2.5 순환기내과
24. 1232009

    제1저자 윤혁 · 교신저자 김나영

    Yoon H, Kim N, Lee BH, Hwang TJ, Lee DH, Park YS, Nam RH, Jung HC, Song IS

    Moxifloxacin-containing triple therapy as second-line treatment for Helicobacter pylori infection: effect of treatment duration and antibiotic resistance on the eradication rate.

    Helicobacter. 2009;14(5):77-85.

    Abstract

    BACKGROUND AND AIM The aim of this study was to evaluate the efficacy of a moxifloxacin-containing triple therapy as second-line treatment for Helicobacter pylori infection. We also investigated the effect of treatment duration and antibiotic resistance on the eradication rate of this therapy.

    METHODS We prospectively enrolled patients found to have persistent H. pylori infections after failure of first-line proton-pump inhibitor-based triple therapy. Patients took moxifloxacin (400 mg q.d.), amoxicillin (1000 mg b.i.d.), and esomeprazole (20 mg b.i.d.). The eradication rate, drug compliance, and adverse event rates were evaluated. Minimal inhibitory tests were performed for moxifloxacin and amoxicillin by the agar dilution method.

    RESULTS In 2004, 41 patients were treated for 7 days. The intention-to-treat and per-protocol eradication rates (ITT/PP) were 75.6/83.8%. Moxifloxacin resistance was 5.6%. Therapy was extended to 10 days during 2005-2006 and 139 patients were treated. The ITT/PP eradication rates were 71.9/82.6%; moxifloxacin resistance had increased to 12%. The final group of 181 patients in 2007-2008 who were treated for 14 days also had low eradication rates (68/79.9%), but there was no statistical significance in the efficacy among the treatment periods. Moxifloxacin resistance in 2007-2008 was 28.2%. Side-effect increased with treatment duration (i.e., 9.8, 12.2, and 25.4% at 7, 10, and 14 days, respectively, p = .001).

    CONCLUSION The 7-day moxifloxacin-containing triple therapy produced an unacceptably low eradication rate. Increasing the duration of therapy was expected to increase the eradication rate, but the expected increased did not materialize, most likely because of coincident marked increase in the prevalence of resistance to moxifloxacin. Tailored treatment based on antibiotic susceptibility testing might be more effective in the achievement of high eradication rate when rapid antibiotic resistance such as moxifloxacin is occurring.

    PubMed IF 4.6 소화기내과
25. 1222009

    제1저자 임수 · 교신저자 박경수

    Lim S, Ahn BY, Chung SS, Park HS, Cho BJ, Kim M, Choi SH, Lee IK, Lee SW, Choi SJ, Chung CH, Cho YM, Lee HK, Park KS

    Effect of a peroxisome proliferator-activated receptor gamma sumoylation mutant on neointimal formation after balloon injury in rats.

    Atherosclerosis. 2009;206(2):411-7.

    Abstract

    Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor regulating inflammation, atherosclerosis, insulin sensitivity and adipogenesis. Recently, it has been discovered that modification by the small ubiquitin-like modifier (SUMO) plays an important role in PPARgamma activity. In the present study, we investigated the effect of sumoylation on the antiatherogenic property of PPARgamma. PPARgamma-K107R sumoylation mutant, PPARgamma-wild type (WT) and control genes were transfected on vascular smooth muscle cells (VSMCs) to compare their effect on the proliferation and migration. Adenoviral vectors expressing the PPARgamma-K107R, PPARgamma-WT or control gene were delivered into the carotid arteries of rats after balloon injury. The PPARgamma-K107R increased the transcriptional activity of peroxisome proliferator response element (PPRE) and had a more potent transcriptional repression activity on the inducible nitric oxide synthase (iNOS) promoter as compared to the other sumoylation mutants or WT. PPARgamma-K107R or WT gene transfer inhibited VSMCs proliferation and migration to a greater extent than the control. The PPARgamma-K107R had more potent activity than PPARgamma-WT in this regard. PPARgamma-K107R or WT transfer showed a significantly lower intima-media ratio (IMR) than the control after balloon injury in rats. Again, the delivery of the PPARgamma-K107R decreased IMR further compared to PPARgamma-WT. In addition, the PPARgamma-K107R transfer showed a lower proliferation index and a higher apoptotic index than PPARgamma-WT. In conclusion, the PPARgamma sumoylation mutant K107R strongly inhibited VSMCs proliferation and migration, sustained apoptosis, and reduced neointimal formation after balloon injury. These results indicate that desumoylation at K107 in PPARgamma might play an important role against atherosclerosis.

    PubMed IF 7.1 내분비대사내과
26. 1212009

    제1저자 최기돈 · 교신저자 김나영

    Choi KD, Kim N, Jang IJ, Park YS, Cho JY, Kim JR, Shin JM, Jung HC, Song IS

    Optimal dose of intravenous pantoprazole in patients with peptic ulcer bleeding requiring endoscopic hemostasis in Korea.

    J Gastroenterol Hepatol. 2009;24(10):1617-24.

    Abstract

    BACKGROUND AND AIM The lowest effective dose of proton pump inhibitors (PPI) for prevention of peptic ulcer rebleeding remains unclear. The objective of the present study was to evaluate whether low-dose PPI has a similar efficacy to high-dose i.v. administration for maintaining intragastric pH above 6.

    METHODS Sixty-one patients with bleeding ulcers were randomized into one of three groups after endoscopic hemostasis: pantoprazole 80 mg bolus followed by 8 mg/h; 40 mg, 4 mg/h infusion; and bolus injection of 40 mg every 24 h. Intragastric pH values and rebleeding rates were measured. In addition, pharmacokinetic parameters and association with CYP2C19 polymorphisms and H. pylori infection were assessed.

    RESULTS Mean percentage of time with intragastric pH > 6, and the proportion of patients with pH > 6 for more than 60% of the time were significantly higher in the 40 mg, 4 mg/h infusion group compared to the 40 mg bolus injection. There was no significant difference between the 80 mg, 8 mg/h and the 40 mg, 4 mg/h groups. In the H. pylori (-) group, only 40% of patients that received continuous infusion reached the target pH > 6 for more than 60% of the time; this was significantly lower than the H. pylori (+) group, 87.5% (P = 0.026).

    CONCLUSIONS A continuous infusion, regardless of high or low dose, was more effective for acid suppression than a 40 mg bolus PPI injection in Korea. H. pylori infection was an important factor for the maintenance of an intragastric pH > 6.

    PubMed IF 3.5 소화기내과
27. 1202009

    제1저자 한혜숙 · 교신저자 임석아

    Han HS, Kim JS, Park JH, Jeon YK, Lee KW, Oh DY, Kim JH, Park SY, Im SA, Kim TY, Park IA, Bang YJ

    Weekly paclitaxel and trastuzumab as a first-line therapy in patients with HER2-overexpressing metastatic breast cancer: magnitude of HER2/neu amplification as a predictive factor for efficacy.

    J Korean Med Sci. 2009;24(5):910-7.

    Abstract

    We evaluated the efficacy and safety of weekly paclitaxel plus trastuzumab as first-line chemotherapy in women with HER2-overexpressing metastatic breast cancer (MBC), and we investigated the prognostic factors including magnitude of HER2/neu amplification in this population. We analyzed 54 patients with HER2-overexpressing MBC that were treated with weekly paclitaxel plus trastuzumab as first-line chemotherapy from February 2004 to December 2006. At a median follow-up of 28 months, median time to progression (TTP) was 16.6 months (95% CI, 9.4 to 23.7 months) and median overall survival was 25.6 months (95% CI, 21.8 to 27.3 months). Therapy was generally well tolerated, although three patients (5.5%) experienced reversible, symptomatic heart failure. Of the 27 patients evaluable for the HER2 FISH, patients with a HER2/CEP17 ratio of < or =4.0 had significantly shorter TTP than those with a HER2/CEP17 ratio of >4.0 (10.8 vs. 23.2 months, P=0.034). A HER2/CEP17 ratio of >4.0 was identified as significant predictive factor of TTP by multivariate analysis (P=0.032). The combination of weekly paclitaxel plus trastuzumab as first-line chemotherapy is an effective regimen in patients with HER2-FISH-positive MBC. Furthermore, the magnitude of HER2 amplification is an independent predictive factor of TTP.

    PubMed IF 3.2 혈액종양내과
28. 1192009

    제1저자 장윤석 · 교신저자 조상헌

    Chang YS, Kim YK, Kwon HS, Park HW, Min KU, Kim YY, Cho SH

    The effect of CpG-oligodeoxynucleotides with different backbone structures and 3' hexameric deoxyriboguanosine run conjugation on the treatment of asthma in mice.

    J Korean Med Sci. 2009;24(5):860-6.

    Abstract

    CpG-Oligodeoxynucleotide (ODN) has two backbones. Phosphorothioate backbone (PS) shows a strong immunostimulating effect while phosphodiester (PE) shows little in vivo. 3' hexameric deoxyriboguanosine-run (3' dG(6)-run) conjugation to PE CpG-ODN has been reported to enhance immunostimulation and to protect against asthma when injected at the time of sensitization in mice. We evaluated the treatment effects of PE and PS CpG-ODN with or without 3' dG(6)-run on asthma in presensitized mice. BALB/c mice sensitized with ovalbumin and alum were challenged with 1% ovalbumin on three days. CpG-ODNs (100 microg) or PBS were injected 4 times; 27 hr before challenge and 3 hr before each challenge (CpG-dG(6): CpG-ODN with 3' dG(6)-run, PE*-CpG-dG(6): PE-CpG-dG(6) with two PS backbones at the 5' terminus). PE-CpG showed no treatment effect. PE-CpG-dG(6) only increased ovalbumin-specific IgG2a. PE*-CpG-dG(6) increased ovalbumin-specific IgG2a but also reduced BAL fluid eosinophils and airway hyperresponsiveness. PS-CpG increased ovalbumin-specific IgG2a, reduced airway inflammation and airway hyperresponsiveness. PS-CpG-dG(6) was less effective than PS-CpG on airway inflammation and airway hyperresponsiveness. In pre-sensitized mice, PE-CpG required not only 3' dG(6)-run but also the modification of two PS linkages at 5' terminus to inhibit features of asthma. PS-CpG was strong enough to inhibit asthma but PS-CpG-dG(6) was less effective.

    PubMed IF 3.2 알레르기내과
29. 1182009

    제1저자 임규형 · 교신저자 오도연

    Lim KH, Oh DY, Chie EK, Jang JY, Im SA, Kim TY, Kim SW, Ha SW, Bang YJ

    Adjuvant concurrent chemoradiation therapy (CCRT) alone versus CCRT followed by adjuvant chemotherapy: which is better in patients with radically resected extrahepatic biliary tract cancer?: a non-randomized, single center study.

    BMC Cancer. 2009;9:345.

    Abstract

    BACKGROUND There is currently no standard adjuvant therapy for patients with curatively resected extrahepatic biliary tract cancer (EHBTC). The aim of this study was to analyze the clinical features and outcomes between patients undergoing adjuvant concurrent chemoradiation therapy (CCRT) alone and those undergoing CCRT followed by adjuvant chemotherapy after curative resection.

    METHODS We included 120 patients with EHBTC who underwent radical resection and then received adjuvant CCRT with or without further adjuvant chemotherapy between 2000 and 2006 at Seoul National University Hospital.

    RESULTS Out of 120 patients, 30 received CCRT alone, and 90 received CCRT followed by adjuvant chemotherapy. Baseline characteristics were comparable between the two groups. Three-year disease-free survival (DFS) rates for CCRT alone and CCRT followed by adjuvant chemotherapy were 26.6% and 45.2% (p = 0.04), respectively, and 3-year overall survival (OS) rates were 30.8% and 62.6% (p < 0.01), respectively. CCRT followed by adjuvant chemotherapy showed longer survival than did CCRT alone, especially in R1 resection (microscopically positive margins) or negative lymph node.

    CONCLUSION Adjuvant CCRT followed by adjuvant chemotherapy prolonged DFS and OS, compared with CCRT alone in patients with curatively resected EHBTC. Adjuvant chemotherapy deserves to consider after adjuvant CCRT. In the future, a randomized prospective study will be needed, with the objective of investigating the role of adjuvant chemotherapy.

    PubMed IF 4.1 혈액종양내과
30. 1172009

    제1저자 김선문 · 교신저자 임춘수

    Kim SM, Chin HJ, Oh YK, Kim YS, Kim S, Lim CS

    Blood pressure-related genes and the progression of IgA nephropathy.

    Nephron Clin Pract. 2009;113(4):c301-8.

    Abstract

    BACKGROUND/AIMS Hypertension is one of the most significant prognostic factors of immunoglobulin A nephropathy (IgAN). We investigated the role of polymorphisms of hypertension-related genes in the clinical impact of IgAN.

    METHODS A total of 238 IgAN and 300 healthy cohorts were studied. The polymorphisms of angiotensinogen (AGT M235T), the angiotensin II type 1 receptor (A1166C), aldosterone synthase (C-344T), alpha-adducin (G460W) and endothelin-1 (K198N and 3A/4A) were determined.

    RESULTS The genotype distributions of the polymorphisms were similar between patients and controls. The individual genotypes taken alone were not associated with the development of hypertension or progression of renal dysfunction. Although AGT M235T was not associated with the development of hypertension in either sex, men with M235T TT were found to be at an increased risk of IgAN progression compared to those with the other genotypes (p = 0.019). In the Cox regression model with adjustment for clinical risk factors, including age at diagnosis, hypertension, serum creatinine and urinary protein excretion at renal biopsy, AGT M235T TT variant was an independent risk factor only for male patients (hazard ratio 5.848; p = 0.005).

    CONCLUSION Our results suggest that the AGT M235T polymorphism is associated with the progression of IgAN in Korean male patients.

    PubMed IF 1.715 신장내과

서울대학교병원 내과 교실이 발표한 SCI 논문입니다. 제목을 누르면 Abstract · 그림 등을, 저자 이름을 누르면 소속 · PubMed · ORCID 를 볼 수 있습니다. 굵은 이름은 동문과 연결된 저자입니다.