SCI 발표논문

전체 4,588편

8082011

제1저자 박진주 · 교신저자 이은봉

, , , , , , , ,
Copy number variation of β-defensin genes in Behçet's disease.
Clin Exp Rheumatol. 2011;29(4 Suppl 67):S20-3.

Abstract
OBJECTIVES Behçet's disease (BD) may be triggered by infectious agents in genetically susceptible persons. Human β-defensin 2 is an inducible antimicrobial peptide, the level of which can be influenced by copy number (CN) of the DEFB4. We investigated the relationship between copy number variation (CNV) of DEFB4 and BD.
METHODS One hundred and ninety-seven patients with BD and 197 healthy controls were enrolled. After measuring CN of DEFB4 with a paralogue ratio test, the CNV was compared between patients and controls. CNV was also analysed in comparison with the clinical manifestations of BD.
RESULTS The CN of DEFB4 was unimodally distributed among the study subjects with mean CN of 4.57 and standard deviation of 1.28. BD samples had numerically lower CN than controls, but the difference was not statistically significant (4.49 ± 1.21 vs. 4.65 ± 1.36, p=0.245). Regarding the relationship between CN of DEFB4 and clinical manifestations, there was no difference of CNV depending on the clinical manifestations.
CONCLUSIONS We found no significant difference in CNV of DEFB4 between patients with BD and controls. Our results suggest that CNV of DEFB4 may not contribute to the pathogenesis of BD.
PubMed IF 3.2 류마티스내과
8072012

제1저자 임수, 김정희 · 교신저자 장학철

, , , , , , , , , ,
Optimal cut points of waist circumference (WC) and visceral fat area (VFA) predicting for metabolic syndrome (MetS) in elderly population in the Korean Longitudinal Study on Health and Aging (KLoSHA).
Arch Gerontol Geriatr. 2012;54(2):e29-34.

Abstract
Optimal cut points of central obesity identifying subjects at risk for MetS were proposed ethnic-specifically, but have not been established yet. Of particular interest are the values for elderly persons, which have not been identified previously. We investigated the appropriate cut points of WC and VFA for elderly in a community-based cohort in Korea. We recruited 294 men and 313 women aged 65 or over who participated in the KLoSHA. A receiver operating characteristic (ROC) curve analysis was used to estimate the optimal cut points of WC and VFA indicative of MetS. The optimal cut points for predicting MetS were 87 cm for WC, 140 cm(2) for VFA in men, and 85 cm for WC, 100 cm(2) for VFA in women with the Youden index. Similar cut points were obtained with the closest-to-(0, 1) criterion except for VFA in men, which was 122 cm(2). When adjusted for age, exercise, smoking, and alcohol consumption, men with ≥122 cm(2) and women with ≥100 cm(2) of VFA had a higher risk of MetS than subjects with lower values. The cut points of VFA and WC at risk for MetS were higher in men than women. In this community-based elderly cohort, the optimal cut points of WC at risk for MetS were lower than the Western criteria. Compared with the cut points in middle-aged Koreans, the cut points for elderly were lower in men and similar in women.
PubMed IF 4.7 내분비대사내과
8062011

제1저자 최성희 · 교신저자 Henry N Ginsberg

,
Increased very low density lipoprotein (VLDL) secretion, hepatic steatosis, and insulin resistance.
Trends Endocrinol Metab. 2011;22(9):353-63.

Abstract
Insulin resistance (IR) affects not only the regulation of carbohydrate metabolism but all aspects of lipid and lipoprotein metabolism. IR is associated with increased secretion of VLDL and increased plasma triglycerides, as well as with hepatic steatosis, despite the increased VLDL secretion. Here we link IR with increased VLDL secretion and hepatic steatosis at both the physiologic and molecular levels. Increased VLDL secretion, together with the downstream effects on high density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) size, is proatherogenic. Hepatic steatosis is a risk factor for steatohepatitis and cirrhosis. Understanding the complex inter-relationships between IR and these abnormalities of liver lipid homeostasis will provide insights relevant to new therapies for these increasing clinical problems.
PubMed IF 20.1 내분비대사내과
8052011

제1저자 이승표 · 교신저자 김용진

, , , , , , , , ,
Deterioration of myocardial function in paradoxical low-flow severe aortic stenosis: two-dimensional strain analysis.
J Am Soc Echocardiogr. 2011;24(9):976-83.

Abstract
BACKGROUND The diagnosis and management of paradoxical low-flow (PLF) aortic stenosis (AS) is challenging in clinical practice. In addition, its pathophysiology has not been fully understood. The aim of this study was to test the hypothesis that left ventricular (LV) myocardial function is deteriorated in PLF AS and that it is closely related to global LV afterload.
METHODS Echocardiographic data from 103 patients with severe AS (aortic valve area < 1.0 cm(2)) with normal LV ejection fractions were prospectively collected. Global longitudinal and circumferential myocardial strain was analyzed using two-dimensional speckle-tracking imaging. PLF AS was defined as a stroke volume index < 35 mL/m(2).
RESULTS Sixteen patients were classified as having PLF AS. Compared with those with normal-flow AS, patients with PLF AS were more likely to have worse functional status (mean New York Heart Association functional class, 2.38 ± 0.70 vs 1.96 ± 0.62; P = .02), worse global longitudinal strain (GLS) (-12.6 ± 4.4% vs -16.4 ± 4.0%, P < .01), lower aortic valve area (0.53 ± 0.15 vs 0.78 ± 0.19 cm(2), P < .01), and higher valvuloarterial impedance (5.62 ± 1.33 vs 3.65 ± 0.83 mm Hg · m(2)/mL, P < .01). GLS showed a significant negative linear relationship with stroke volume index (r = -0.324, P = .001) and a positive relationship with E/E' ratio (r = 0.367, P < .001). Multivariate analysis showed that age (β = 0.08, P = .07) and valvuloarterial impedance (β = 1.54, P < .01) were significant predictors of GLS.
CONCLUSIONS GLS is depressed in patients with PLF AS. This implies that subclinical myocardial dysfunction may be more prominent in PLF AS compared with normal-flow AS and suggests the possible diagnostic and prognostic value of two-dimensional global strain in identifying PLF AS. In addition, global LV afterload is an important determinant of myocardial dysfunction in patients with severe AS.
PubMed IF 8.3 순환기내과
8042011

제1저자 성기철, 임수 · 교신저자 성기철

, ,
Hyperinsulinemia and homeostasis model assessment of insulin resistance as predictors of hypertension: a 5-year follow-up study of Korean sample.
Am J Hypertens. 2011;24(9):1041-5.

Abstract
BACKGROUND The relationships between insulin level and indexes of insulin resistance (IR) to predict incident hypertension have been explored only in cross-sectional or prospective studies with small numbers of patients. We investigated whether plasma insulin concentration and the homeostasis model assessment of insulin resistance (HOMA(IR)) are associated with the onset of hypertension in a population of apparently healthy and relatively lean Korean adults.
METHODS We selected 10,894 of 15,638 subjects who were normotensive at baseline during general health status evaluations in 2003 and 2008. The baseline and follow-up examinations included analyses of fasting glucose, insulin level, and lipid profile. Alcohol consumption, smoking status, exercise habits, and education level were also evaluated using a standard questionnaire.
RESULTS Of the 10,894 subjects, hypertension developed in 881 (8.1%) during the ensuing 5 years. Incident hypertension was more common among older subjects than it was in younger subjects and was associated with a high baseline body mass index (BMI). In multivariable logistic models, elevated serum insulin, and HOMA(IR) were associated with an increased risk of incident hypertension in both sexes. In a multivariable analysis using quartiles of insulin and HOMA(IR), the odds ratio (OR) for incident hypertension was the highest in the highest quartile of insulin and HOMA(IR). The highest quartile of insulin and HOMA(IR) was associated with a 1.5-1.7 times increased risk of incident hypertension.
CONCLUSIONS This 5-year follow-up study provides evidence that both a high circulating insulin level and HOMA(IR) are significant risk factors for the development of hypertension in a relatively lean and healthy population.
PubMed IF 2.9 내분비대사내과
8032011

제1저자 박민정 · 교신저자 김동희

, , , , , , , , , , ,
Association between Helicobacter pylori Seropositivity and the Coronary Artery Calcium Score in a Screening Population.
Gut Liver. 2011;5(3):321-7.

Abstract
BACKGROUND/AIMS Helicobacter pylori causes numerous extragastric manifestations, including coronary heart disease. The coronary artery calcification (CAC) score, measured using computed tomography (CT) has been used as a screening test for coronary atherosclerosis. This study investigated the association between H. pylori seropositivity and CAC scores in a screening population.
METHODS Patients who underwent a health checkup between October 2003 and July 2007 and who did not have a history of ischemic heart disease were enrolled in the study. Subjects were screened with a multidetector CT scan to determine the CAC score and for anti-H. pylori antibody immunoglobulin G; traditional risks for coronary heart disease were evaluated using a structured questionnaire, anthropometric measurements, and laboratory tests.
RESULTS Of the 2,029 subjects enrolled (1,295 males), 1,214 (59.8%) subjects were H. pylori positive and 815 were H. pylori negative. There were no significant differences in the baseline characteristics of the seropositive and seronegative patients. When the CAC presence or absence scores were considered, multivariate analysis revealed that H. pylori seropositivity was statistically associated with the presence of CAC and that this association was stronger in the mild CAC score category.
CONCLUSIONS H. pylori seropositive patients are at a higher risk for coronary atherosclerosis regardless of traditional cardiovascular risk factors. This association is particularly applicable for early coronary atherosclerosis.
PubMed IF 4.1 소화기내과
8022011

제1저자 김학령 · 교신저자 김학령

, , , , , ,
The positive association between peripheral blood cell counts and bone mineral density in postmenopausal women.
Yonsei Med J. 2011;52(5):739-45.

Abstract
PURPOSE Accumulating evidence has shown a close connection between hematopoiesis and bone formation. Our aim was to evaluate the association between peripheral blood cell counts and bone mineral density (BMD) in a sample of postmenopausal women.
MATERIALS AND METHODS Three hundreds thirty eight healthy postmenopausal women who underwent BMD measurement during their health check-up were investigated. BMD was measured by dual energy X-ray asorptiometry at L1-L4 spine, femoral neck and total proximal femur. BMD was expressed as a T-score: among T-scores obtained from three different sites (L1-L4 spine, femoral neck and total proximal femur), the lowest T-score was considered to be the subject's T-score.
RESULTS The prevalence of osteopenia and osteoporosis diagnosed by T-score in the study participants were 49.4% (167/338) and 5.0% (17/338), respectively. Peripheral blood white blood cell (WBC), red blood cell (RBC) and platelet counts had significant positive correlations with T-scores (p<0.001) upon simple linear regression analysis. A multiple linear regression analysis, after controlling of confounders including age, body weight, systolic blood pressure, alkaline phosphatase and creatinine, showed that WBC (β=0.127; standard error=0.043; p=0.014), RBC (β=0.192; standard error=0.139; p<0.001) and platelet (β=0.097; standard error=0.001; p=0.050) counts still had significant positive association with T-scores.
CONCLUSION The study results showed a positive relationship between blood cell counts and bone mineral density in postmenopausal women, supporting the idea of a close connection between hematopoiesis and bone formation. The study results also suggest that blood cell counts could be a putative marker for estimating BMD in postmenopausal women.
PubMed IF 3.1 순환기내과
8012011

제1저자 배준설 · 교신저자 김윤준

, , , , , , , , , , ,
Genetic analysis of complement component 9 (C9) polymorphisms with clearance of hepatitis B virus infection.
Dig Dis Sci. 2011;56(9):2735-41.

Abstract
BACKGROUND The complement component 9 (C9), a major cytolytic protein in the complement system, plays an important role in the immunological process. However, associations between genetic variations of the complement factor and chronic hepatitis B virus infection still need to be investigated.
AIMS We hypothesized that genetic variations in the complement component 9 gene can influence the clearance of chronic hepatitis B virus infection, hepatocellular carcinoma occurrence, and onset age of hepatocellular carcinoma. To investigate the relationship between complement component 9 variations and these disease phenotypes, we performed a case-control association analysis in a Korean population.
METHODS Genetic variations were identified through direct DNA sequencing and genotyped using TaqMan assay (n = 1,103). In order to investigate the relationship of complement component 9 with chronic hepatitis B virus clearance and hepatocellular carcinoma occurrence, differences in SNP and haplotype frequency distributions were analyzed using logistic and multiple regression analyses with adjusted age and gender as covariates.
RESULTS Although +23189C>T polymorphism in exon 4 and C9_ht2 [T-G-C-A-C] were significantly associated with clearance of chronic hepatitis B virus infection and hepatocellular carcinoma occurrence, the association signals were not retained after multiple testing corrections.
CONCLUSIONS We conclude that variations in the complement component 9 gene are unlikely to influence clearance of chronic hepatitis B virus infection and hepatocellular carcinoma occurrence. Although this preliminary result provides meaningful information, further functional investigations in other genetic factors for pathway analyses are required.
PubMed IF 2.8 소화기내과
8002011

제1저자 김영선 · 교신저자 김동희

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Differentiating small polyp histologies using real-time screening colonoscopy with Fuji Intelligent Color Enhancement.
Clin Gastroenterol Hepatol. 2011;9(9):744-749.e1.

Abstract
BACKGROUND & AIMS There are limited data describing the performance of Fuji Intelligent Color Enhancement (FICE, EC 590 ZW; Fujinon Inc, Saitama, Japan) for differentiating polyp histologies during screening colonoscopy. We evaluated the ability of an endoscopist to diagnose small polyp histology during a screening colonoscopy using FICE.
METHODS A prospective study was performed on 763 consecutive, asymptomatic subjects who were undergoing screening colonoscopy. Pit patterns and vascular patterns were used to predict the histology of 525 polyps (mean size, 4.5 ± 2.2 mm, 315 adenomas) of less than 10 mm using FICE with high magnification and without. The performances of the FICE analyses were calculated and compared with the results from the histopathology.
RESULTS The overall accuracy achieved by FICE with high magnification in the diagnosis of adenomas of less than 10 mm (87.0%) was significantly greater than that achieved without high magnification (80.4%; P < .05). Moreover, the improvement of accuracy attained when using high-magnification FICE was most pronounced and significant compared without using high-magnification FICE in the diagnosis for diminutive polyps (≤5 mm; 85.4% vs 79.1%; P < .05). Among all types of adenomas, the sensitivity of FICE was lowest for sessile serrated adenomas (38.5% vs 89.4%; P < .01), even when FICE was used with high magnification.
CONCLUSIONS FICE with high magnification is better for differentiating the histology of small polyps during screening colonoscopy than FICE without high magnification, especially for diminutive polyps. Large-scale studies are needed to improve the identification of serrated adenomas and small diminutive polyps using FICE.
PubMed IF 16.2 소화기내과
7992011

제1저자 박경우 · 교신저자 김효수

, , , , , , , , , , , , , ,
Sirolimus- vs. paclitaxel-eluting stents for the treatment of unprotected left main coronary artery stenosis: complete 2-year follow-up of a two-center registry.
Int J Cardiol. 2011;151(1):89-95.

Abstract
BACKGROUND The feasibility of percutaneous coronary intervention (PCI) using drug-eluting stents and its comparability with bypass surgery in treatment of unprotected left main coronary artery (LMCA) stenosis has been shown previously. We compared the mid-to long-term outcome between sirolimus-(SES) vs. paclitaxel-eluting stents (PES) in an all-comer analysis that included all patients with unprotected LMCA stenosis who underwent PCI with SES or PES.
METHODS From March 2003 and June 2007, 196 patients underwent PCI with SES or PES for unprotected LMCA stenosis at Seoul National University Main or Bundang Hospital; SES was implanted in 141 patients and PES in 55 patients. The baseline clinical and procedural characteristics were mostly similar between the SES and PES group.
RESULTS After 2 years of follow-up, there were no differences in the rate of cardiac death (9.1% vs. 8.5%) and nonfatal MI (5.5% vs. 2.8%) between the two groups. However, the risk of repeat revascularization tended to be lower in the SES group compared with the PES group [TLR, 9.9% vs. 20.0% (P=0.06); TVR, 17.7% vs. 30.9% (P=0.05)], which did not reach statistical significance. The rate of stent thrombosis (ST) was also similar between the two groups (3.6% vs. 2.1% for definite ST, 3.6% vs. 2.8% for definite+probable ST).
CONCLUSIONS In all-comers undergoing first generation DES implantation for unprotected LMCA stenosis, PES and SES showed comparable 2-year clinical results regarding hard endpoints and major adverse cardiac events.
PubMed IF 3.3 순환기내과
7982011

제1저자 서정원 · 교신저자 김효수

, , , , , , , , , ,
Comparison of antiplatelet effect and tolerability of clopidogrel resinate with clopidogrel bisulfate in patients with coronary heart disease (CHD) or CHD-equivalent risks: a phase IV, prospective, double-dummy, parallel-group, 4-week noninferiority trial.
Clin Ther. 2011;33(8):1057-68.

Abstract
BACKGROUND Clopidogrel resinate is a resinate complex of (+)-clopidogrel optical isomer, wherein the (+)-clopidogrel isomer binds to a water-soluble cation exchange resin via sulfonic acid groups. It was approved by the Korean Food and Drug Administration on the basis of a Phase I study that demonstrated the bioequivalence of clopidogrel resinate and clopidogrel bisulfate. However, there are no available data regarding efficacy and tolerability in patients with vascular disease.
OBJECTIVE The goal of this study was to investigate the antiplatelet efficacy and tolerability of clopidogrel resinate in patients with coronary heart disease (CHD) or CHD-equivalent risks.
METHODS This study was a Phase IV, randomized, double-blind, double-dummy, parallel-group, noninferiority trial. We prospectively recruited patients in 10 centers between March 2008 and July 2008. Patients who had documented CHD or CHD-equivalent risks were randomly assigned to 1 of 3 groups: group A, aspirin (100 mg) + clopidogrel bisulfate placebo + clopidogrel resinate placebo; group B, aspirin (100 mg) + clopidogrel bisulfate placebo + clopidogrel resinate (75 mg); or group C, aspirin (100 mg) + clopidogrel bisulfate (75 mg) + clopidogrel resinate placebo. The primary outcome was the percent P2Y(12) inhibition after medication, assessed by using a point-of-care assay. If the 1-sided 90% upper confidence limit for the difference was less than the prespecified delta value (-5.7), clopidogrel resinate would be considered noninferior to clopidogrel bisulfate. The secondary outcome, the prevalence of adverse events (AEs) associated with study medications, was assessed at each visit by direct interview.
RESULTS A total of 314 patients (mean [SD] age, 62.2 [9.0] years; male 63.7%; weight, 67.3 [13.6] kg [range, 45-102 kg]; all Asian) were enrolled, and 287 patients finished the study (group A, n = 97; group B, n = 90; and group C, n = 100). Eight patients took no study medications and were excluded from the tolerability and efficacy analyses. Nineteen patients discontinued the study because of protocol violation (n = 15), adverse events (n = 3), or voluntary withdrawal (n = 1) and were excluded from the efficacy analysis. There were no significant differences in baseline clinical characteristics among the groups except for the frequency of a history of CHD (group A, 85.4%; group B, 73.0%; and group C, 88.3%; P = 0.01). Patients treated with either type of clopidogrel showed significant inhibition (mean [SD]) of P2Y(12) (group A, -5.9% [15.1%]; group B, 23.4% [21.9%]; and group C, 19.5% [23.8%]; P < 0.001). Differences between clopidogrel resinate and clopidogrel bisulfate in the inhibition of P2Y(12) did not exceed the predetermined value for inferiority (P for noninferiority, 0.02; 90% CI, -0.9 to 10.3). In the tolerability analysis, there was no mortality during the study period and no significant differences between groups in the frequency of AEs and serious AEs (AEs: group A, 33.0%; group B, 26.0%; and group C, 23.3% [P = 0.27]; serious AEs: group A, 1.0%; group B, 3.0%; and group C, 1.0% [P = 0.42]). One patient in group B underwent coronary stent implantation for treatment of stable angina.
CONCLUSIONS In this small, selected Asian patient population, differences in the platelet inhibition efficacies of clopidogrel resinate and clopidogrel bisulfate did not exceed the predetermined limits for noninferiority. The differences in tolerability between the 2 drugs did not reach statistical significance.
PubMed IF 3.7 순환기내과
7972011

제1저자 이정원 · 교신저자 김나영

, , , , , ,
Mutations of Helicobacter pylori associated with fluoroquinolone resistance in Korea.
Helicobacter. 2011;16(4):301-10.

Abstract
BACKGROUND AND AIM Fluoroquinolone resistance of Helicobacter pylori is known to be dependent on mutations in the QRDR of gyrA. This study was performed to investigate the distribution of gyrA point mutations and to evaluate the impact of the mutations on second-line H. pylori eradication therapy.
METHODS After H. pylori isolation from gastric mucosal specimens, fluoroquinolone resistance was examined using the agar dilution method. DNA sequencing of the QRDR of gyrA was performed in 89 fluoroquinolone-resistant and 27 fluoroquinolone-susceptible isolates. Transformation experiments were performed to confirm mutations in the resistant strains. The eradication rates of moxifloxacin-containing triple therapy were evaluated depending on the resistance of fluoroquinolone.
RESULTS The gyrA mutations were detected in 75.3% (55 of 73 strains) of the primary resistant strains and 100% (16 strains) of the secondary resistant strains. The most common mutations were Asp-91 (36.0%) and Asn-87 (33.7%). The MIC values in the transformed strains differed depending on the gyrA mutations, N87, and D91. Six patients with fluoroquinolone-resistant strains received moxifloxacin-containing triple therapy as the second-line therapy, and two of three patients with Asn-87 mutations (66.7%) failed in the eradication. By contrast, three patients with Asp-91 mutations had successful eradication treatment.
CONCLUSIONS Fluoroquinolone resistance of H. pylori was caused by gyrA Asn-87 and Asp-91 point mutations. The Asn-87 mutation seems to be an important determinant of failure of fluoroquinolone-containing triple eradication therapy based on eradication results.
PubMed IF 4.6 소화기내과
7962011

제1저자 정재우 · 교신저자 조상헌

, , , , , , ,
The potential inhibitory effect of revaprazan, an acid pump antagonist, on anticoagulation with warfarin.
Tohoku J Exp Med. 2011;224(4):293-300.

Abstract
Revaprazan is the first acid pump antagonist with a function similar to that of proton pump inhibitors (PPIs). It has a dual action, active suppression of gastric acid secretion and gastric mucosa protection. While PPIs are known to enhance the prolongation of prothrombin time by warfarin, no research has been done on the drug interaction between revaprazan and warfarin. This study was conducted in order to verify the potential drug interaction between revaprazan and warfarin. Omeprazole, a representative PPI, was used as the control for revaprazan. We searched for patients who were given either revaprazan or omeprazole along with warfarin using the medical record database of Seoul National University Hospital between July 2007 and June 2010. Among the 15 patients who took revaprazan and warfarin together, 73.3% (11/15) showed more than 30% reduction of anticoagulation effect by warfarin after revaprazan was added. The revaprazan group showed a significant shortening of prothrombin time during revaprazan administration compared to pre- and post-revaprazan medication (P < 0.05) while the omeprazole group did not show such difference. Revaprazan seems to have cumulative dose-dependent anti-warfarin or anti-coagulation effect, as judged from the fact that the longer medication with revaprazan showed correlation with the shortening of prothrombin time (R = -0.632, P < 0.05). This study shows a possible interaction between revaprazan and warfarin and suggests that revaprazan can cause shortening of prothrombin time. Therefore, when revaprazan is prescribed to patients on warfarin therapy, prothrombin time should be frequently monitored.
PubMed IF 1.5 알레르기내과
7952011

제1저자 이지연 · 교신저자 김영환

, , , , , , , , , , , ,
Risk factors of postoperative pneumonia after lung cancer surgery.
J Korean Med Sci. 2011;26(8):979-84.

Abstract
The purpose of this study was to investigate risk factors of postoperative pneumonia (POP) after lung cancer surgery. The 417 lung cancer patients who underwent surgical resection in a tertiary referral hospital were included. Clinical, radiological and laboratory data were reviewed retrospectively. Male and female ratio was 267:150 (median age, 65 yr). The incidence of POP was 6.2% (26 of 417) and in-hospital mortality was 27% among those patients. By univariate analysis, age ≥ 70 yr (P < 0.001), male sex (P = 0.002), ever-smoker (P < 0.001), anesthesia time ≥ 4.2 hr (P = 0.043), intraoperative red blood cells (RBC) transfusion (P = 0.004), presence of postoperative complications other than pneumonia (P = 0.020), forced expiratory volume in 1 second/forced vital capacity (FEV(1)/FVC) < 70% (P = 0.002), diffusing capacity of the lung for carbon monoxide < 80% predicted (P = 0.015) and preoperative levels of serum C-reactive protein ≥ 0.15 mg/dL (P = 0.001) were related with risk of POP. Multivariate analysis showed that age ≥ 70 yr (OR = 3.563, P = 0.014), intraoperative RBC transfusion (OR = 4.669, P = 0.033), the presence of postoperative complications other than pneumonia (OR = 3.032, P = 0.046), and FEV(1)/FVC < 70% (OR = 3.898, P = 0.011) were independent risk factors of POP. In conclusion, patients with advanced age, intraoperative RBC transfusion, postoperative complications other than pneumonia and a decreased FEV(1)/FVC ratio have a higher risk for pneumonia after lung cancer surgery.
PubMed IF 3.2 호흡기내과
7942011

제1저자 김여명 · 교신저자 정숙향

, , , , , , , , ,
Chronic hepatitis B, non-Hodgkin's lymphoma, and effect of prophylactic antiviral therapy.
J Clin Virol. 2011;51(4):241-5.

Abstract
BACKGROUND Hepatitis B virus (HBV) infection can be associated with non-Hodgkin's lymphoma (NHL), and prophylactic antiviral therapy is recommended for NHL patients with chronic HBV infection who are receiving anticancer chemotherapy.
OBJECTIVES The aims of this study were to investigate the association between HBV infection and NHL, and to evaluate the application rate and the effect of prophylactic antiviral therapy for HBV-infected NHL patients.
STUDY DESIGN A retrospective, case-control study was performed.
RESULTS The prevalence of hepatitis B surface antigen in 344 patients who were consecutively diagnosed with NHL from May 2003 to October 2009 (44 of 344; 12.8%) was significantly higher than that of 688 age- and sex-matched health-check examinees (24 of 688; 3.5%) (adjusted odds ratio, 4.08; 95% confidence interval, 2.44-6.85). T cell type NHL, as well as B cell type, showed a significant association with HBV carrier rate. Among 32 NHL patients who received anticancer chemotherapy, 30 patients (93.8%) received prophylactic antiviral therapy, primarily lamivudine. However, HBV DNA monitoring during antiviral therapy was frequently omitted in hemato-oncology clinics. While there was no occurrence of hepatitis flare during antiviral therapy, withdrawal hepatitis after discontinuation of antiviral drug occurred frequently (60%).
CONCLUSION HBV may play a significant role in development of NHL, which prompts further study on the lymphomagenic mechanism of HBV infection. Prophylactic antiviral therapy was administered during chemotherapy to almost all of the NHL patients with HBV infection; however, further investigation should be conducted for determination of optimal duration and monitoring of antiviral therapy.
PubMed IF 3.7 소화기내과
7932011

제1저자 박경선 · 교신저자 김인호

, , , , , , ,
Identification and functional characterization of ion channels in CD34(+) hematopoietic stem cells from human peripheral blood.
Mol Cells. 2011;32(2):181-8.

Abstract
Hematopoietic stem cells (HSCs) are used therapeutically for hematological diseases and may also serve as a source for nonhematopoietic tissue engineering in the future. In other cell types, ion channels have been investigated as potential targets for the regulation of proliferation and differentiation. However, the ion channels of HSCs remain elusive. Here, we functionally characterized the ion channels of CD34(+) cells from human peripheral blood. Using fluorescence-activated cell sorting, we confirmed that the CD34(+) cells also express CD45 and CD133. In the CD34(+)/CD45(+)/CD133(high) HSCs, RT-PCR of 58 ion channel mRNAs revealed the coexpression of Kv1.3, Kv7.1, Nav1.7, TASK2, TALK2, TWIK2, TRPC4, TRPC6, TRPM2, TRPM7, and TRPV2. Whole-cell patch clamp recordings identified voltage-gated K(+) currents (putatively Kv1.3), pH-sensitive TASK2-like back-ground K(+) currents, ADP-ribose-activated TRPM2 currents, temperature-sensitive TRPV2-like currents, and diacylglycerol-analogue-activated TRPC6-like currents. Our results lend new insight into the physiological role of ion channels in HSCs, the specific implications of which require further investigation.
PubMed IF 8.2 혈액종양내과
7922011

제1저자 이충희 · 교신저자 오세일

, , , , ,
Generating radiofrequency ablation lesions using magnetically coupled bipolar catheters.
Pacing Clin Electrophysiol. 2011;34(8):934-8.

Abstract
BACKGROUND Transmural lesions are difficult to produce in myocardial regions with thick walls, such as the left ventricle (LV), using conventional radiofrequency (RF) ablation catheters. This study was performed to evaluate the efficacy of magnetically coupled bipolar catheters and compare the performance with conventional unipolar and bipolar RF ablation catheters.
METHODS AND RESULTS Neodymium magnets assembled in ablation catheters were used to facilitate tissue contact in a bipolar RF ablation system. In vitro sheets of porcine skeletal muscle, with 10-mm thickness, were ablated with a 4-mm-tip unipolar RF ablation catheter (UA), a bipolar ablation system (BA) using a pair of 4-mm-tip catheters, and a magnetically coupled bipolar system (MB). The RF generator setting was 50 W and 90°C. RF energy was delivered for 30 or 60 seconds and five lesions were created in each ablation condition. The bottom side of the skeletal-muscle sheet was exposed to saline at 37°C and a flow of 5.6 L/min, mimicking the LV endocardial surface. The top side was exposed to air, mimicking the epicardial surface. In the 60-second ablation cases, the transmuralities were 0%, 0%, and 40% (UA, BA, and MB, respectively). The volumes of the lesions were 61.5 ± 8.5, 224.3 ± 51.8, and 359.3 ± 93.8 mm(3) (UA, BA, and MB, respectively).
CONCLUSIONS The magnetically coupled bipolar RF ablation system created transmural lesions more efficiently than the conventional ablation system, primarily due to higher RF current density and stronger tissue contact. This prototype method could be applied to the development of novel ablation devices for thick areas of tissue.
PubMed IF 1.3 순환기내과
7912011

제1저자 오세일 · 교신저자 오세일

, , ,
Botulinum toxin injection in epicardial autonomic ganglia temporarily suppresses vagally mediated atrial fibrillation.
Circ Arrhythm Electrophysiol. 2011;4(4):560-5.

Abstract
BACKGROUND Autonomic denervation may suppress atrial fibrillation (AF) vulnerability. This study was designed to assess the short- to mid-term effects of botulinum toxin, a cholinergic neurotransmission blocker, on AF inducibility.
METHODS AND RESULTS A total of 23 mongrel dogs were studied. The sinus node and atrioventricular node epicardial fat pads were exposed through a right lateral thoracotomy. Botulinum toxin (Botox, 50 U per fat pad) or 0.9% normal saline (control) was injected into the center of each of the 2 fat pads. The electrophysiological effects were evaluated at 1, 2, and 3 weeks (7 to 8 animals at each time point) with and without cervical vagal stimulation. The vagal stimulation effects on the sinus and atrioventricular nodes were inhibited, and dispersion of atrial effective refractory period was lower at 1 week in the Botox group. Significant suppression of AF inducibility was observed at 1 week but disappeared at 2 and 3 weeks. These changes were not observed in the control group.
CONCLUSIONS Temporary suppression of vagally mediated AF, for at least 1 week, was achieved with botulinum toxin injection in this canine model. This effect might be associated with reduced dispersion of effective refractory period. A temporary autonomic block using botulinum toxin might be a novel therapeutic option for several clinical conditions such as post-cardiac surgery AF.
PubMed IF 9.3 순환기내과
7902011

제1저자 이준규 · 교신저자 류지곤

, , , , , , , , ,
Effects and mechanisms of the combination of suberoylanilide hydroxamic acid and bortezomib on the anticancer property of gemcitabine in pancreatic cancer.
Pancreas. 2011;40(6):966-73.

Abstract
OBJECTIVES Earlier studies that dealt with the combination therapy of gemcitabine and histone deacetylation inhibitors for pancreatic cancer revealed unsatisfactory results. The activation of nuclear factor κB (NF-κB) was referred as one of the attributable causes, and we attempted to overcome this resistance by the addition of a proteasome inhibitor.
METHODS The influences of suberoylanilide hydroxamic acid (vorinostat, SAHA), a histone deacetylase inhibitor, and bortezomib, a novel selective antagonist of 26S proteasome, with or without gemcitabine on cell growth and apoptosis and the expressions of related proteins were observed in pancreatic cancer cell lines (MiaPaCa-2 and ASPC-1). The xenograft model of pancreatic cancer was used to notice effects in vivo.
RESULTS Vorinostat and bortezomib had independent inhibitory effects and potentiated the antitumor property of gemcitabine in vitro. In the xenograft model, more augmented effects were achieved when bortezomib was combined with gemcitabine than gemcitabine alone. The down-regulation of pAkt and suppression of NF-κB activity was induced by the triple combination.
CONCLUSIONS The triple combination of vorinostat, bortezomib, and gemcitabine resulted in the strongest antitumor effects both in vitro and in vivo and pAkt and NF-κB seems to be involved in this process.
PubMed IF 2.2 소화기내과
7892011

제1저자 허은영 · 교신저자 윤호일

, , , , ,
Surgical resection of highly suspicious pulmonary nodules without a tissue diagnosis.
Jpn J Clin Oncol. 2011;41(8):1017-22.

Abstract
OBJECTIVE The safety and efficacy of surgical resection of lung nodule without tissue diagnosis is controversial. We evaluated direct surgical resection of highly suspicious pulmonary nodules and the clinical and radiological predictors of malignancy.
METHODS Retrospective analyses were performed on 113 patients who underwent surgical resection without prior tissue diagnosis for highly suspicious pulmonary nodules. Clinical and radiological characteristics were compared between histologically proven benign and malignant nodules after resection. Total costs, length of hospitalization and waiting time to surgery were compared with those of patients who had tissue diagnosis prior to surgery.
RESULTS Among 280 patients with pulmonary nodules suspicious for lung cancer, 113 (40.4%) underwent operation without prior tissue diagnosis. Lung nodules were diagnosed as malignant in 96 (85%) of the 113 patients. Except for forced expiratory volume in 1 s, clinical characteristics were not significantly different according to the pathologic results. Forty-five (90%) of 50 patients with ground-glass opacity nodules had a malignancy. Mixed ground-glass opacity, bubble lucency, irregular margin and larger size correlated with malignancy in ground-glass opacity nodules (P<0.05). Fifty-one (81%) of 67 patients with solid nodules had a malignancy. Spiculation, pre-contrast attenuation and contrast enhancement significantly correlated with malignancy in solid nodules (P<0.05). Surgical resection without tissue diagnosis significantly decreased total costs, hospital stay and waiting time (P<0.05).
CONCLUSIONS Direct surgical resection of highly suspicious pulmonary nodules can be a valid procedure. However, careful patient selection and further investigations are required to justify direct surgical resection.
PubMed IF 2.5 호흡기내과
7882011

제1저자 송영욱 · 교신저자 박경숙

, , , , , ,
T-cell immunoglobulin and mucin domain 3 genetic polymorphisms are associated with rheumatoid arthritis independent of a shared epitope status.
Hum Immunol. 2011;72(8):652-5.

Abstract
The aim of this study was to investigate T-cell immunoglobulin and mucin domain 3 (TIM3) genetic polymorphisms and rheumatoid arthritis (RA) according to the shared epitope (SE) status. Six single nucleotide polymorphisms (SNPs: rs11742259 [C/T], rs10515746 [C/A], rs35960726 [A/G], rs1036199 [A/C], rs4704846 [A/G], and rs11134551 [A/G]) in the TIM3 gene from 366 RA patients and 389 healthy controls were investigated using the real-time polymerase chain reaction method. Associations between these SNPs and clinical manifestations (including SE status) were investigated using the SPSS program and Haploview. Polymorphisms of rs35690726 (AG+ GG vs AA: 8.2% vs 1.8%, p(c) < 0.001) were significantly associated with RA with or without SE (p(c) < 0.001 or p(c) = 0.009, respectively). Polymorphisms of rs11742259 (p(c) = 0.003) and rs1036199 (p(c) = 0.012) were significantly different in RA patients with SE, but not in those without SE. In haplotype analysis with a permutation test for the first 4 SNPs (rs11742259, rs10515746, rs35690726, and, rs1036199), CCAA, CCGA, CCGC, and CAAA haplotypes were significantly associated with RA. The clinical characteristics of RA patients were not significantly associated with any TIM3 polymorphism. TIM3 genetic polymorphisms may have a role in the development of RA regardless of a shared epitope status.
PubMed IF 2.1 류마티스내과
7872011

제1저자 구현경 · 교신저자 김영환

, , , , , , , , , , ,
Factors associated with recurrence in patients with curatively resected stage I-II lung cancer.
Lung Cancer. 2011;73(2):222-9.

Abstract
BACKGROUND Patients with stage I-II non-small cell lung cancer (NSCLC) show variability in recurrence after curative resection. Several factors have been proposed as prognostic of recurrence in previous studies. However, because of the heterogeneity of the populations studied, these reports did not yield consistent results. The aim of our study was to identify risk factors for recurrence in patients with curatively resected stage I-II NSCLC.
METHODS We reviewed the medical records of pathological stage I-II NSCLC patients after curative surgery performed in a tertiary referral center (Seoul National University Hospital) from January 2002 to December 2004. Demographic factors, radiological, histopathological, and laboratory findings, and surgery-related factors were analyzed. Patients with invasive cancer other than lung cancer that was present 5 years prior to surgery were excluded. The Cox proportional hazard regression model was used for multivariate analyses.
RESULTS Three hundred and ten patients were included. Among them, local recurrence occurred in 27 patients (8.7%), whereas distant recurrence occurred in 79 patients (25.5%). Adenocarcinoma histology (OR, 2.74; 95% CI, 1.14-6.58; P=0.024), carcinoembryonic antigen (CEA) level>2.3 ng/mL (OR, 2.26; 95% CI, 1.02-5.00; P=0.045), and standard uptake values (SUV) of tumor in positron emission tomography (PET)>4.5 (OR, 5.45; 95% CI, 1.82-16.31; P=0.002) were independent predictors of recurrence in addition to TNM stage. We also constructed a recurrence prediction model based on these findings, which yielded better diagnostic performance than the TNM staging system.
CONCLUSION Adenocarcinoma histology, CEA level, and SUV of PET could be considered as prognostic factors for recurrence in patients with curatively resected stage I-II NSCLC.
PubMed IF 5.3 호흡기내과
7862011

제1저자 최정민 · 교신저자 김상균

, , , , , , , , ,
Lymph node metastasis in multiple synchronous early gastric cancer.
Gastrointest Endosc. 2011;74(2):276-84.

Abstract
BACKGROUND Although endoscopic resection for early gastric cancer (EGC) is increasingly available, it has not been determined whether indications for endoscopic resection are equally acceptable for multiple EGCs.
OBJECTIVE To compare the various clinicopathologic factors and risk of lymph node (LN) metastasis between multiple and solitary EGCs.
DESIGN Case-control study.
SETTING University hospital.
PATIENTS This study involved 1717 patients with 156 multiple and 1561 solitary EGCs.
INTERVENTION Gastrectomy with LN dissection.
MAIN OUTCOME MEASUREMENTS Incidence of LN metastasis.
RESULTS In multiple EGCs, main lesions had larger tumor size and deeper invasion depth than the accessory lesions (P < .001). The clinicopathologic features of multiple EGCs were similar to those of solitary EGCs with respect to tumor size, depth of invasion, lymphovascular invasion, and incidence of LN metastasis. Importantly, the risk of LN metastasis in multiple EGCs that met the indication criteria for endoscopic resection was not significantly different from that in solitary EGCs. Tumors meeting conventional indications for endoscopic resection had no risk of LN metastasis, whereas tumors meeting expanded indications showed a similar risk of LN metastasis in the two groups. In multiple EGCs, tumor size ≥3 cm and lymphovascular invasion were independent risk factors of LN metastasis.
LIMITATIONS Small number of patients with multiple EGCs studied.
CONCLUSION Multiple EGCs had clinicopathologic characteristics and risk of LN metastasis similar to those of solitary EGCs. Endoscopic resection may be adopted as curative treatment for multiple EGCs that meet indications for endoscopic resection. Further studies are needed to verify the present study results.
PubMed IF 8 소화기내과
7852011

제1저자 박경일 · 교신저자 김형관

, , , , , , , , ,
Incremental prognostic value of early postoperative right ventricular systolic function in patients undergoing surgery for isolated severe tricuspid regurgitation.
Heart. 2011;97(16):1319-25.

Abstract
BACKGROUND Preoperative right ventricular end-systolic area (RV-ESA) and haemoglobin level have been suggested to be independent predictors of long-term prognosis in patients undergoing corrective surgery for isolated severe tricuspid regurgitation (TR).
AIMS To investigate whether early postoperative echocardiography provides useful prognostic information in addition to preoperative clinical and echocardiographic variables.
METHODS 69 consecutive patients undergoing corrective surgery for isolated severe TR (60 women, mean 57.6±8.9 years) were studied. Comprehensive preoperative echocardiography was performed in all patients, with early postoperative echocardiography in all patients except one. During follow-up (median 40 months, range 6-86 months), clinical events were investigated, defined as operative mortality, cardiovascular death, repeated open heart surgery and readmission due to cardiovascular problems.
RESULTS 28 patients (41%) were categorised as New York Heart Association class II, 36 (52%) as III and 5 (7%) as IV. 63 patients (91.3%) had undergone prior left-sided valve surgery. Seven (10.1%) patients died before discharge. Of the remaining 62 patients, three died during follow-up, and eight required readmission due to cardiovascular problems. On multivariate analyses using clinical and preoperative variables, RV-ESA (p=0.006) and haemoglobin level (p<0.001) were independent predictors of event-free survival. When early postoperative echocardiography variables were included, preoperative haemoglobin and early postoperative RV-FAC were predictors of long-term event-free survival. On receiver-operating characteristic curve analysis, early postoperative RV-FAC≥31% predicted event-free survival with a sensitivity of 90% and a specificity of 83% (p<0.001). The addition of early postoperative echocardiographic RV-FAC markedly improved the prognostic utility of the model containing preoperative haemoglobin level and echocardiographic RV-ESA (p<0.001).
CONCLUSION Early postoperative RV-FAC, measured by echocardiography, provided valuable information additional to preoperative RV-ESA and hemoglobin level that was useful for predicting long-term clinical events following corrective TR surgery.
PubMed IF 4.4 순환기내과
7842011

제1저자 류지곤 · 교신저자 Maitra A

, , , , , , , , , ,
Elevated microRNA miR-21 levels in pancreatic cyst fluid are predictive of mucinous precursor lesions of ductal adenocarcinoma.
Pancreatology. 2011;11(3):343-50.

Abstract
BACKGROUND Biomarkers for the diagnostic classification of pancreatic cysts are urgently needed. Deregulated microRNA (miRNAs) expression is widespread in pancreatic cancer. We assessed whether aberrant miRNAs in pancreatic cyst fluid could be used as potential biomarkers for cystic precursor lesions of pancreatic cancer.
METHODS Cyst fluid specimens were prospectively collected from 40 surgically resected pancreatic cysts, and small RNAs were extracted. The 'mucinous' cohort included 14 intraductal papillary mucinous neoplasms (including 3 with an associated adenocarcinoma) and 10 mucinous cystic neoplasms; the 'nonmucinous' cohort included 11 serous cystadenomas and 5 other benign cysts. Quantitative reverse transcription PCR was performed for five miRNAs (miR-21, miR-155, miR-221, miR-17-3p, miR-191), which were previously reported as overexpressed in pancreatic adenocarcinomas.
RESULTS Significantly higher expression of miR-21, miR-221, and miR-17-3p was observed in the mucinous versus nonmucinous cysts (p < 0.01), with the mean relative fold differences being 7.0-, 7.9-, and 5.4-fold, respectively. Receiver operating characteristic curves demonstrated the highest median area under the curve for miR-21, with a median specificity of 76%, at a sensitivity of 80%.
CONCLUSION This pilot study demonstrates that profiling miRNAs in pancreatic cyst fluid samples is feasible and can yield potential biomarkers for the classification of cystic lesions of the pancreas. and IAP.
PubMed IF 3.9 소화기내과
7832011

제1저자 이세원, 원주윤 · 교신저자 김효수

, , , , , , , , , ,
Angiopoietin-1 protects heart against ischemia/reperfusion injury through VE-cadherin dephosphorylation and myocardiac integrin-β1/ERK/caspase-9 phosphorylation cascade.
Mol Med. 2011;17(9-10):1095-106.

Abstract
Early reperfusion after myocardial ischemia that is essential for tissue salvage also causes myocardial and vascular injury. Cardioprotection during reperfusion therapy is an essential aspect of treating myocardial infarction. Angiopoietin-1 is an endothelial-specific angiogenic factor. The potential effects of angiopoietin-1 on cardiomyocytes and vascular cells undergoing reperfusion have not been investigated. We propose a protective mechanism whereby angiopoietin-1 increases the integrity of the endothelial lining and exerts a direct survival effect on cardiomyocytes under myocardial ischemia followed by reperfusion. First, we found that angiopoietin-1 prevents vascular leakage through regulating vascular endothelial (VE)-cadherin phosphorylation. The membrane expression of VE-cadherin was markedly decreased on hypoxia/reoxygenation but was restored by angiopoietin-1 treatment. Interestingly, these effects were mediated by the facilitated binding between SH2 domain-containing tyrosine phosphatase (SHP2) or receptor protein tyrosine phosphatase μ (PTPμ) and VE-cadherin, leading to dephosphorylation of VE-cadherin. siRNA against SHP2 or PTPμ abolished the effect of angiopoietin-1 on VE-cadherin dephosphorylation and thereby decreased levels of membrane-localized VE-cadherin. Second, we found that angiopoietin-1 prevented cardiomyocyte death, although cardiomyocytes lack the angiopoietin-1 receptor Tie2. Angiopoietin-1 increased cardiomyocyte survival through integrin-β1-mediated extracellular signal-regulated kinase (ERK) phosphorylation, which inhibited caspase-9 through phosphorylation at Thr¹²⁵ and subsequently reduced active caspase-3. Neutralizing antibody against integrin-β1 blocked these protective effects. In a mouse myocardial ischemia/reperfusion model, angiopoietin-1 enhanced cardiac function and reduction in left ventricular-end systolic dimension (LV-ESD) and left ventricular-end diastolic dimension (LV-EDD) with an increase in ejection fraction (EF) and fractional shortening (FS). Our findings suggest the novel cardioprotective mechanisms of angiopoietin-1 that are achieved by reducing both vascular leakage and cardiomyocyte death after ischemia/reperfusion injury.
PubMed IF 8.3 순환기내과
7822011

제1저자 박영주, 이유진 · 교신저자 장혁재

, , , , ,
Impact of subclinical hypothyroidism on the coronary artery disease in apparently healthy subjects.
Eur J Endocrinol. 2011;165(1):115-21.

Abstract
OBJECTIVE Cardiovascular disease (CVD) occurs frequently and may progress more rapidly in overt hypothyroidism (OVH). However, the role of mild thyroid failure as a risk factor for CVD is not clear. This study is aimed at exploring the association between subclinical hypothyroidism (SCH) and coronary artery disease (CAD), as detected by cardiac computed tomography (CT), in apparently healthy subjects.
SUBJECTS AND METHODS We retrospectively enrolled 2404 asymptomatic subjects who underwent cardiac CT with an intermediate to high risk (Framingham 10-year risk ≥10%) of developing CAD but with no known CAD or thyroid disease. Coronary artery calcium score (CACS) was assessed by calcium scan, and the presence of the plaques (CAD), with ≥50% stenosis being indicative of obstructive CAD, was assessed by coronary CT angiography.
RESULTS Of the 2404 subjects, 2355 subjects were euthyroid (Eu; 53±9 years, 83 females) and 49 had SCH (58±12 years, seven females). CAD and CACS >100 were more prevalent in SCH subjects than in Eu subjects (Eu vs SCH: CAD, 948 (40.6%) vs 31 (63.3%), P=0.002; CACS >100, 239 (10.3%) vs 10 (20.4%), P=0.031). SCH was also an independent risk factor for CAD after a multivariate analysis (odds ratio: 2.125, 95% confidence interval: 1.049-4.307, P=0.036).
CONCLUSIONS SCH subjects who were at an intermediate-to-high risk of developing CAD were significantly more likely to exhibit occult CAD than Eu subjects, especially in men with SCH. These findings suggest that mild thyroid failure also independently contributes to the development of CAD.
PubMed IF 6.7 내분비대사내과
7812011

제1저자 김달래 · 교신저자 이춘택

, , , , , , , ,
Combination of vorinostat and adenovirus-TRAIL exhibits a synergistic antitumor effect by increasing transduction and transcription of TRAIL in lung cancer cells.
Cancer Gene Ther. 2011;18(7):467-77.

Abstract
Soluble TRAIL and adenovirus (ad)-TRAIL exhibit a strong antitumor effect by inducing apoptosis. Vorinostat is the histone deacetylase (HDAC) inhibitor that induces cell death in cancer cell lines and regulates the expression of epigenetically silenced genes, such as Coxackie adenoviral receptor (CAR), the receptor for adenoviral entry. We propose a new strategy in which vorinostat will induce high expression of ad-TRAIL and a strong antitumor response, and investigated the mechanism involved. The effect of vorinostat on transcription and expression of TRAIL from ad-TRAIL-transduced lung cancer cells were confirmed by reverse transciption-PCR (RT-PCR), quantitative real time-PCR and western blot assay. Anti-tumor effects were measured after cotreatment of vorinostat and ad-TRAIL, and the drug interactions were analyzed. After combined treatment of vorinostat and ad-TRAIL, apoptosis and western blot assays for Akt, Bcl-2 and caspase were performed. Vorinostat increased the expression of CAR in lung cancer cell lines and increased the expression of luciferase (luc) from ad-luc-transduced cells and TRAIL from ad-TRAIL-transduced cells. RT-PCR and quantitative real time-PCR, after sequential vorinostat treatment, revealed that vorinostat may enhance TRAIL expression from ad-TRAIL by increasing transduction through enhanced CAR expression and increasing adenoviral transgene transcription. Combined vorinostat and ad-TRAIL treatment showed the synergistic anti-tumor effect in lung cancer cell lines. Combined vorinostat and ad-TRAIL induced stronger apoptosis induction, suppression of NF-κB activation and breakdown of the anti-apoptotic molecule Bcl-2. In conclusion, the vorinostat synergistically enhanced the anti-tumor effect of ad-TRAIL by (1) increasing adenoviral transduction through the increased expression of CAR and (2) increasing adenoviral transgene (TRAIL) transcription in lung cancer cell lines.
PubMed IF 6.4 호흡기내과
7802011

제1저자 김홍일 · 교신저자 조영민

, , , , , , , ,
Gender differences in diagnostic values of visceral fat area and waist circumference for predicting metabolic syndrome in Koreans.
J Korean Med Sci. 2011;26(7):906-13.

Abstract
Abdominal fat accumulation is known to be strongly implicated in development of metabolic syndrome (MetS). We examined diagnostic values of obesity-related parameters in 95 men and 185 women, and we determined optimal cutoff values of visceral fat area (VFA) and waist circumference (WC) for predicting the presence of multiple non-adipose components of MetS. Receiver operating characteristic (ROC) curve analysis revealed that VFA was the best indicator of MetS. WC and VFA exhibited similar diagnostic values for men and postmenopausal women, whereas WC was inferior to VFA for premenopausal women (area under ROC curve of VFA and WC was 0.76 and 0.52, respectively; P < 0.001). Optimal cutoff points of VFA and WC for predicting MetS were 136 cm(2) and 89 cm in men and 95 cm(2) and 82 cm in women, respectively. Subjects with VFA and WC above these cutoff values exhibited increased insulin resistance and increased carotid intima-media thickness. In conclusion, WC has a diagnostic value similar to VFA for predicting MetS in men and postmenopausal women, but not in premenopausal women. Further studies are necessary to develop a simple clinical parameter that reflects visceral fat in premenopausal women.
PubMed IF 3.2 내분비대사내과
7792011

제1저자 고성준 · 교신저자 김주성

, , , , , ,
Fluoxetine inhibits NF-κB signaling in intestinal epithelial cells and ameliorates experimental colitis and colitis-associated colon cancer in mice.
Am J Physiol Gastrointest Liver Physiol. 2011;301(1):G9-19.

Abstract
Although fluoxetine, a selective serotonin reuptake inhibitor, is known to demonstrate anti-inflammatory activity, little information is available on the effect of fluoxetine regarding intestinal inflammation. This study investigates the role of fluoxetine in the attenuation of acute murine colitis by suppression of the NF-κB pathway in intestinal epithelial cells (IEC). Fluoxetine significantly inhibited activated NF-κB signals and the upregulated expression of interleukin-8 (IL-8) in COLO 205 colon epithelial cells stimulated with tumor necrosis factor-α (TNF-α). Pretreatment with fluoxetine attenuated the increased IκB kinase (IKK) and IκBα phosphorylation induced by TNF-α. In a murine model, administration of fluoxetine significantly reduced the severity of dextran sulfate sodium (DSS)-induced colitis, as assessed by the disease activity index, colon length, and histology. In addition, the DSS-induced phospho-IKK activation, myeloperoxidase activity, a parameter of neutrophil accumulation, and the secretion of macrophage-inflammatory protein-2, a mouse homolog of IL-8, were significantly decreased in fluoxetine-pretreated mice. Moreover, fluoxetine significantly attenuated the development of colon cancer in mice inoculated with azoxymethane and DSS. These results indicate that fluoxetine inhibits NF-κB activation in IEC and that it ameliorates DSS-induced acute murine colitis and colitis-associated tumorigenesis, suggesting that fluoxetine is a potential therapeutic agent for the treatment of inflammatory bowel disease.
PubMed IF 3 소화기내과

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