SCI 발표논문

전체 4,588편

11982013

제1저자 이경훈 · 교신저자 김태유

, , , , , , , , , , , , , , , , , , ,
Pharmacogenetic analysis of adjuvant FOLFOX for Korean patients with colon cancer.
Cancer Chemother Pharmacol. 2013;71(4):843-51.

Abstract
PURPOSE Ethnic diversity of genetic polymorphism can result in individual differences in the efficacy and toxicity of cancer chemotherapy.
METHODS We analyzed 20 germline polymorphisms in 10 genes (TS, MTHFR, ERCC1, XPD, XRCC1, ABCC2, AGXT, GSTP1, GSTT1 and GSTM1) from prospectively enrolled 292 Korean patients treated with adjuvant oxaliplatin plus leucovorin plus 5-fluorouracil (FOLFOX) for colon cancer.
RESULTS In contrast to previous studies in Caucasians, neutropenia (grade 3-4, 60.5 %) was frequently observed, whereas only 16.4 % experienced grade 2 or more sensory neuropathy. Neutropenia was more frequent in MTHFR 677TT [adjusted odds ratio (OR) 2.32, 95 % confidence interval (CI) 1.19-4.55] and ERCC1 19007TT (adjusted OR 4.58, 95 % CI 1.20-17.40) genotypes. Patients harboring XRCC1 23885GG experienced less grade 2-4 neuropathy [adjusted OR 0.52, 95 % CI 0.27-0.99]. MTHFR 677TT (p = 0.002) and XRCC1 23885GG (p = 0.146) genotypes were also more prevalent in Koreans compared to Caucasians. TS 'low' genotype (adjusted HR 1.83, 95 % CI 1.003-3.34) was significantly related to shorter disease-free survival. Overall survival was not significantly different according to the polymorphisms.
CONCLUSIONS Polymorphisms in MTHFR, XRCC1 and TS are related to toxicities and disease-free survival in patients with colon cancer. The ethnic differences in frequencies of genotypes may explain the ethnic difference in toxicity profile following adjuvant FOLFOX chemotherapy.
PubMed IF 2.5 혈액종양내과
11972013

제1저자 김정희 · 교신저자 신찬수

, , , , , , ,
Thigh muscle attenuation measured by computed tomography was associated with the risk of low bone density in community-dwelling elderly population.
Clin Endocrinol (Oxf). 2013;78(4):512-7.

Abstract
OBJECTIVES Although muscle mass has been shown to be positively related with bone mineral density (BMD), there are only a few studies that investigated the association between muscle strength or muscle quality and BMD. We investigated the effects of muscle strength and muscle fat infiltration, as a measure of muscle quality, adjusted for muscle mass on femoral neck BMD in Korean elderly cohort.
METHODS We recruited 242 men and 231 women aged over 65 years who participated in the Korean Longitudinal Study on Health and Ageing. Leg muscle mass and femoral neck BMD were measured by dual-energy X-ray absorptiometry. Isokinetic strength of knee extensors was measured as a peak torque value by an isokinetic device. Computed tomography scan of the mid-thigh measured the mean Hounsfield unit (HU) of the lean tissue. Low bone density was defined as femoral neck T-score ≤-2·0.
RESULTS Leg muscle mass, knee extensor strength and thigh muscle HU values were significantly positively correlated with femoral neck BMD in both men and women. However, muscle strength was not a significant determinant for the presence of low bone mass after adjusting for muscle mass in multiple logistic regression analyses. Notably, thigh muscle HU values were strong and independent determinant for the risk of low bone density.
CONCLUSION Decreased thigh muscle HU values, a measure of fatty infiltration of muscle, were independently associated with increased risk of low bone density in the elderly population.
PubMed IF 2.8 내분비대사내과
11962013

제1저자 김소연/김태민 · 교신저자 김동완

, , , , , , , ,
Heterogeneity of genetic changes associated with acquired crizotinib resistance in ALK-rearranged lung cancer.
J Thorac Oncol. 2013;8(4):415-22.

Abstract
BACKGROUND Anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is markedly sensitive to the ALK inhibitor crizotinib. However, acquired resistance to crizotinib is inevitable through several mechanisms. Therefore, this study was conducted to identify genetic alterations associated with crizotinib resistance.
METHODS Tumor samples were derived from seven ALK-positive NSCLC patients who showed acquired resistance to crizotinib, and these patients were analyzed for ALK, EGFR, and KRAS mutations and ALK and EGFR gene amplifications. In vitro cytotoxicity of crizotinib and ALK downstream signals were compared between crizotinib-naive and -resistant NSCLC cells.
RESULTS After a median duration of 6 months (range, 4-12 months), seven ALK-positive NSCLC patients developed acquired resistance to crizotinib. Three patients harbored secondary ALK mutations, including one patient with both mutations: L1196M (n = 2) and G1269A (n = 2). Of note, one patient displayed ALK gene copy number gain (4.1-fold increase compared with the pre-crizotinib specimen) and EGFR L858R mutation with high polysomy. The amphiregulin concentration was high in the supernatant fluid from five patients with malignant pleural effusion (116.4-18934.0 pg/ml). SNU-2535 cells derived from a patient who harbored the G1269 mutation were resistant to crizotinib treatment similar to H3122 CR1 cells. L1196M and G1269A mutant clones were less sensitive to crizotinib and ALK downstream signals were ineffectively suppressed in these clones.
CONCLUSIONS Genetic changes associated with crizotinib resistance are heterogeneous in ALK-rearranged NSCLC patients who respond to crizotinib and subsequently develop resistance.
PubMed IF 23.3 혈액종양내과
11952013

제1저자 이준구 · 교신저자 임석아

, , , , , , , , , , , , , ,
Efficacy of exemestane in korean patients with metastatic breast cancer after failure of nonsteroidal aromatase inhibitors.
J Breast Cancer. 2013;16(1):66-71.

Abstract
PURPOSE Exemestane has shown good efficacy and tolerability in postmenopausal women with hormone receptor-positive metastatic breast cancer. However, clinical outcomes in Korean patients have not yet been reported.
METHODS Data on 112 postmenopausal women with metastatic breast cancer were obtained retrospectively. Clinicopathological characteristics and treatment history were extracted from medical records. All patients received 25 mg exemestane daily until objective disease progression. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR=complete response+partial response+stable disease for 6 months).
RESULTS The median age of the subjects was 55 years (range, 28-76 years). Exemestane treatment resulted in a median PFS of 5.7 months (95% confidence interval [CI], 4.4-7.0 months) and median OS of 21.9 months (95% CI, 13.6-30.3 months). ORR was 6.4% and CBR was 46.4% for the 110 patients with evaluable lesions. Symptomatic visceral disease was independently associated with shorter PFS (hazard ratio, 3.611; 95% CI, 1.904-6.848; p<0.001), compared with bone-dominant disease in a multivariate analysis of PFS after adjusting for age, hormone receptor, human epidermal growth factor receptor 2, Ki-67 status, dominant metastasis site, and sensitivity to nonsteroidal aromatase inhibitor (AI) treatment. Sensitivity to previous nonsteroidal AI treatment was not associated with PFS, suggesting no cross-resistance between exemestane and nonsteroidal AIs.
CONCLUSION Exemestane was effective in postmenopausal Korean women with hormone receptor-positive metastatic breast cancer who failed previous nonsteroidal AI treatment.
PubMed IF 3.6 혈액종양내과
11942013

제1저자 박준빈 · 교신저자 최수연

, , , ,
Relation between cardio-ankle vascular index and coronary artery calcification or stenosis in asymptomatic subjects.
J Atheroscler Thromb. 2013;20(6):557-67.

Abstract
AIM The cardio-ankle vascular index (CAVI) is an index of arterial stiffness. We investigated the association of CAVI with the severity of coronary artery calcification (CAC) and coronary stenosis by coronary computed tomography angiography (CTA) in an asymptomatic population.
METHODS A total of 549 asymptomatic Korean individuals who underwent CAVI and CTA were analyzed retrospectively. CAC and coronary stenosis were measured by CTA and assessed for the correlation with CAVI.
RESULTS The degree of CAC and coronary stenosis demonstrated a significant correlation with CAVI (r= 0.187, p<0.001 and r= 0.212, p<0.001 for the CAC score and stenosis, respectively). After adjustment for potential confounders, including age, gender, hypertension, diabetes mellitus, and dyslipidemia, a predefined cutoff value of CAVI ≥8 was associated with advanced CAC (CAC ≥300) and significant coronary stenosis (stenosis ≥50%). Specifically, the adjusted odds ratio (95% confidence interval) of CAC ≥300 and coronary stenosis ≥50% was 3.57 (1.92-6.66) and 2.81 (1.13-7.00), respectively. Additional inclusion of CAVI improved the predictive power of the receiver operating characteristic curves for predicting coronary atherosclerosis based on traditional risk factors; the area under the curve for predicting CAC ≥300 and coronary stenosis ≥50% increased from 0.739 to 0.791 (p for difference= 0.023), and from 0.761 to 0.842 (p= 0.032), respectively.
CONCLUSIONS CAVI reflects coronary atherosclerosis and may be used as a screening tool for assessing subclinical atherosclerotic burden in an asymptomatic population.
PubMed IF 3.4 순환기내과
11932013

제1저자 김민혜 · 교신저자 강혜련

, ,
The usefulness of job relocation and serum eosinophil cationic protein in baker's asthma.
Int Arch Allergy Immunol. 2013;161(3):252-7.

Abstract
BACKGROUND Although the most widely recommended treatment for occupational asthma is to completely avoid the causative agents, job relocation within the same company is often substituted for a complete career change. However, there is not much data on the efficacy of job relocation within the workplace and appropriate follow-up parameters. We investigated baker's asthma patients to validate the efficacy of job relocation and follow-up markers.
METHODS Twelve bakery plant workers diagnosed with baker's asthma were enrolled in the study. Asthma-related symptoms and methacholine provocation test were followed up 6 months after a job relocation. Skin prick test and ELISA to detect wheat flour-specific IgE and eosinophil cationic protein (ECP) in sputum and serum were also followed up to evaluate the status of allergic inflammation.
RESULTS After a 6-month job relocation, all 12 workers showed an improvement in symptoms, and airway hyperresponsiveness to methacholine was negatively converted in 9 of them. There were no significant differences in skin reactivity and serum flour-specific IgE levels before and after the relocation. While sputum ECP levels did not show a significant difference (338.3 ± 93.0 μg/l vs. 175.0 ± 78.9 μg/l, p = 0.118), there was a remarkable difference in serum ECP levels before and after the relocation (12.2 ± 3.0 μg/l vs. 2.8 ± 3.1 μg/l, p = 0.004).
CONCLUSIONS Job relocation was effective in managing baker's asthma. Serum ECP level was a useful follow-up marker of baker's asthma.
PubMed IF 2.3 알레르기내과
11922013

제1저자 김태민/팽진철 · 교신저자 허대석

, , , , , , , , , , ,
Total lesion glycolysis in positron emission tomography is a better predictor of outcome than the International Prognostic Index for patients with diffuse large B cell lymphoma.
Cancer. 2013;119(6):1195-202.

Abstract
BACKGROUND This study was undertaken to evaluate the prognostic value of quantitative metabolic parameters in [(18) F]2-fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) for diffuse large B cell lymphoma (DLBCL).
METHODS A total of 140 DLBCL patients underwent FDG-PET scans before rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy. The maximal standardized uptake value (SUVmax ) and total lesion glycolysis (TLG) were calculated, with the margin thresholds as 25%, 50%, and 75% of SUVmax of all lesions. Treatment outcomes were compared between groups according to metabolic parameters and the International Prognostic Index (IPI).
RESULTS After a median follow-up of 28.5 months (range, 5-81 months), the 2-year progression-free survival (PFS) and overall survival (OS) were 83% and 87%, respectively. Among metabolic parameters, TLG at the threshold of 50% (TLG50 ) was significantly associated with treatment outcomes. High TLG50 values (>415.5) were associated with reduced survivals compared with low TLG50 values (≤415.5) (2-year PFS of 73% versus 92%, P = .007; and 2-year OS of 81% versus 93%, P = .031). High IPI score (≥3) significantly reduced OS (2-year OS of 79% versus 90%, P = .049). Ann Arbor stage III/IV adversely affected PFS (P = .013). However, high IPI score and Ann Arbor stage of III/V did not significantly shorten PFS (P = .200) and OS (P = .921), respectively. High TLG50 values independently predicted survivals by multivariate analysis (hazard ratio = 4.4; 95% confidence interval = 1.5-13.1; P = .008 for PFS and hazard ratio = 3.1; 95% confidence interval = 1.0-9.6; P = .049 for OS).
CONCLUSIONS Combined assessment of volume and metabolism (ie, TLG) is predictive of survivals in DLBCL patients who are treated with R-CHOP. Cancer 2013. © 2012 American Cancer Society.
PubMed IF 5.6 혈액종양내과
11912013

제1저자 고성준 · 교신저자 임종필

, , , , , , ,
Long-term outcome in patients with obscure gastrointestinal bleeding after negative capsule endoscopy.
World J Gastroenterol. 2013;19(10):1632-8.

Abstract
AIM To investigate long-term outcome in obscure gastrointestinal bleeding (OGIB) after negative capsule endoscopy (CE) and identify risk factors for rebleeding.
METHODS A total of 113 consecutive patients underwent CE for OGIB from May 2003 to June 2010 at Seoul National University Hospital. Ninety-five patients (84.1%) with a subsequent follow-up after CE of at least 6 mo were enrolled in this study. Follow-up data were obtained from the patients' medical records. The CE images were reviewed by two board-certified gastroenterologists and consensus diagnosis was used in all cases. The primary outcome measure was the detection of rebleeding after CE, and factors associated with rebleeding were evaluated using multivariate analysis.
RESULTS Of the 95 enrolled patients (median age 61 years, range 17-85 years), 62 patients (65.3%) were male. The median duration of follow-up was 23.7 mo (range 6.0-89.4 mo). Seventy-three patients (76.8%) underwent CE for obscure-overt bleeding. Complete examination of the small bowel was achieved in 77 cases (81.1%). Significant lesions were found in 38 patients (40.0%). The overall rebleeding rate was 28.4%. The rebleeding rate was higher in patients with positive CE (36.8%) than in those with negative CE (22.8%). However, there was no significant difference in cumulative rebleeding rates between the two groups (log rank test; P = 0.205). Anticoagulation after CE examination was an independent risk factor for rebleeding (hazard ratio, 5.019; 95%CI, 1.560-16.145; P = 0.007), regardless of CE results.
CONCLUSION Patients with OGIB and negative CE have a potential risk of rebleeding. Therefore, close observation is required and alternative modalities should be considered in suspicious cases.
PubMed IF 7.7 소화기내과
11902013

제1저자 안동원 · 교신저자 류지곤

, , , , , ,
Endoscopic papillectomy for benign ampullary neoplasms: how can treatment outcome be predicted?
Gut Liver. 2013;7(2):239-45.

Abstract
BACKGROUND/AIMS Endoscopic papillectomy is increasingly performed with curative intent for benign papillary tumors. This study was performed to identify factors that predict the presence of malignancy and affect endoscopic success.
METHODS We retrospectively analyzed the medical records of patients who received an endoscopic papillectomy for papillary adenoma from 2006 to 2009.
RESULTS A total of 43 patients received endoscopic papillectomy. The pathologic results after papillectomy revealed adenocarcinoma in five patients (12%), and the risk of malignancy was high in cases of large lesions, preprocedural pathology of high-grade dysplasia or high serum alkaline phosphatase. Endoscopic success was observed in 37 patients (86%) at the end of follow-up (mean duration, 10.4±9.6 months). The factor significantly affecting success was a complete resection at the initial papillectomy (p=0.007). Two patients experienced recurrence 10 and 32 months after the complete resection, but both achieved endoscopic success with repeated endoscopic treatment. Six patients with endoscopic failure received surgical resection.
CONCLUSIONS Endoscopic papillectomy is a safe and effective method for the curative resection of benign papillary tumors, especially when complete resection is achieved at the initial papillectomy. Follow-up with surveillance should be performed for at least 3 years because of the possible recurrence of tumors during these periods.
PubMed IF 4.1 소화기내과
11892013

제1저자 윤혁 · 교신저자 김상균

, , ,
High Recurrence Rate of Idiopathic Peptic Ulcers in Long-Term Follow-up.
Gut Liver. 2013;7(2):175-81.

Abstract
BACKGROUND/AIMS Our aim was to compare the long-term clinical outcomes of idiopathic peptic ulcer disease (IPUD) with those of Helicobacter pylori-positive and nonsteroidal anti-inflammatory drug (NSAID)-induced peptic ulcer disease (PUD).
METHODS Patients with endoscopically diagnosed PUD were retrospectively reviewed. According to their H. pylori-infection status and history of NSAIDs use, patients were categorized into three groups: H. pylori-positive PUD, NSAID-induced PUD, and IPUD. Clinical outcomes were analyzed, and the recurrence rate of PUD was compared among the three groups.
RESULTS A total of 238 patients were enrolled. Those with IPUD, NSAID-induced PUD, and H. pylori-positive PUD comprised of 56, 60, and 122 patients, respectively. The 5-year cumulative incidences of recurrent ulcers were 24.3% (95% confidence interval [CI], 11.6% to 37.0%) in IPUD, 10.9% (95% CI, 2.6% to 19.2%) in NSAID-induced PUD, and 3.8% (95% CI, 0.1% to 7.5%) in H. pylori-positive PUD (IPUD vs NSAID-induced PUD/H. pylori-positive PUD, p=0.43/p<0.001 by log-rank test). In the Cox-proportional hazards model, only IPUD remained as an independent risk factor associated with recurrent ulcers (hazard ratio, 5.97; 95% CI, 1.94 to 18.34; p=0.002).
CONCLUSIONS IPUD exhibited a higher recurrence rate than H. pylori-positive and NSAID-induced PUD in long-term follow-up and was an independent risk factor for ulcer recurrence.
PubMed IF 4.1 소화기내과
11882013

제1저자 김서윤 · 교신저자 김덕겸

, , , , , , ,
Clinical effects of gemifloxacin on the delay of tuberculosis treatment.
J Korean Med Sci. 2013;28(3):378-82.

Abstract
Although gemifloxacin has low in vitro activity against Mycobacterium tuberculosis, the effect of gemifloxacin on the delay of tuberculosis (TB) treatment has not been validated in a clinical setting. The study group included patients with culture-confirmed pulmonary TB who initially received gemifloxacin for suspected community-acquired pneumonia (CAP). Two control groups contained patients treated with other fluoroquinolones or nonfluoroquinolone antibiotics. Sixteen cases were treated with gemifloxacin for suspected CAP before TB diagnosis. Sixteen and 32 patients were treated with other fluoroquinolones and nonfluoroquinolones, respectively. The median period from the initiation of antibiotics to the administration of anti-TB medication was nine days in the gemifloxacin group, which was significantly different from the other fluoroquinolones group (35 days). The median times for the nonfluoroquinolone group and the gemifloxacin group were not significantly different. There were no significant differences between the gemifloxacin and other fluoroquinolone group in terms of symptomatic and radiographic improvements. However, the frequency of radiographic improvement in the other fluoroquinolones group tended to be higher than in the gemifloxacin group. Gemifloxacin might be the preferred fluoroquinolone for treating CAP, to alleviate any concerns about delaying TB treatment.
PubMed IF 3.2 호흡기내과
11872013

제1저자 황정환 · 교신저자 김남중

, , , , , , , , , , ,
Incidence and risk factors of tuberculosis in patients with human immunodeficiency virus infection.
J Korean Med Sci. 2013;28(3):374-7.

Abstract
Korea is a low prevalence country for human immunodeficiency virus (HIV) infection and has an intermediate tuberculosis (TB) burden. We previously reported that the incidence of TB in HIV-infected patients was 9.6 cases per 100 person-years (P-Y) between 1988 and 1997. The aims of the present study were to measure any change in incidence from the previous study, and to identify risk factors for TB in HIV-infected patients. We reviewed all medical records of HIV-infected patients who were followed-up in one tertiary hospital between 1998 and 2010. Over the total observation period of 5858.33 P-Y, TB developed in 70 patients (1.19 cases per 100 P-Y; 95% confidence interval [CI], 0.91-1.47 cases per 100 P-Y). Based on Poisson regression, one risk factor associated with TB was an initial CD4+ cell count below 200 cells/µL (relative risk, 2.34; 95% CI, 1.47-3.73). Mean CD4+ cell counts of pulmonary, extrapulmonary, and both pulmonary and extrapulmonary TB were 179.8 cells/µL, 138.3 cells/µL, and 114.2 cells/µL, respectively (P = 0.55). In conclusion, the incidence of TB in HIV-infected patients has decreased since the previous study. An initial CD4+ cell count below 200 cells/µL is an independent risk factor for development of TB in HIV-infected patients.
PubMed IF 3.2 감염내과
11862013

제1저자 박준빈 · 교신저자 김효수

, , , , , , , ,
Serum alkaline phosphatase is a predictor of mortality, myocardial infarction, or stent thrombosis after implantation of coronary drug-eluting stent.
Eur Heart J. 2013;34(12):920-31.

Abstract
AIMS The association between alkaline phosphatase (ALP) and mortality was reported in several subgroups of patients. But, the role of ALP in overall coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI) remains unknown. The aim of this study was to examine the prognostic value of the ALP level in patients with CAD who underwent PCI with drug-eluting stent (DES).
METHODS AND RESULTS We prospectively included CAD patients who underwent PCI with DES. After exclusion of patients with liver disease and cancer, 1636 patients were selected for the analysis of clinical outcomes (median duration of follow-up; 762 days, inter-quartile range; 494-1068 days), and were classified into tertiles by baseline measurements of ALP (<63, 63-78, and >78 IU/L). After adjustment of potential confounders including angiographic data, the independent and dose-dependent association was observed between tertile of ALP and the adjusted hazard ratio (HR) of all-cause mortality (P for trend < 0.0001). Specifically, compared with the lowest ALP tertile, the adjusted HR of all-cause mortality in the highest tertile was 4.21 (95% confidence interval 2.03-8.71). In subgroup of patients with stable or unstable angina, a similar association was noted (P for trend < 0.0001). In terms of cardiovascular mortality, myocardial infarction, and stent thrombosis, the adjusted HRs in the highest ALP tertile were 3.92 (1.37-11.20), 1.98 (0.91-4.29), and 2.73 (1.33-5.61), respectively, compared with the lowest tertile. Furthermore, evaluation of both ALP and C-reactive protein provided better predictive value than either alone. Interesting result suggesting the mechanism was that ALP was significantly associated with the presence of angiographic coronary calcification (P for trend = 0.046).
CONCLUSION Our study demonstrated that the higher serum ALP level is an independent predictor of mortality, myocardial infarction, and stent thrombosis in CAD patients after PCI with DES.
PubMed IF 45.3 순환기내과
11852013

제1저자 박경우 외 3인 (외부) · 교신저자 이종영

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
A genome-wide association study of a coronary artery disease risk variant.
J Hum Genet. 2013;58(3):120-6.

Abstract
Although over 30 common genetic susceptibility loci have been identified to be independently associated with coronary artery disease (CAD) risk through genome-wide association studies (GWAS), genetic risk variants reported to date explain only a small fraction of heritability. To identify novel susceptibility variants for CAD and confirm those previously identified in European population, GWAS and a replication study were performed in the Koreans and Japanese. In the discovery stage, we genotyped 2123 cases and 3591 controls with 521 786 SNPs using the Affymetrix SNP Array 6.0 chips in Korean. In the replication, direct genotyping was performed using 3052 cases and 4976 controls from the KItaNagoya Genome study of Japan with 14 selected SNPs. To maximize the coverage of the genome, imputation was performed based on 1000 Genome JPT+CHB and 5.1 million SNPs were retained. CAD association was replicated for three GWAS-identified loci (1p13.3/SORT1 (rs599839), 9p21.3/CDKN2A/2B (rs4977574), and 11q22.3/ PDGFD (rs974819)) in Koreans. From GWAS and a replication, SNP rs3782889 showed a strong association (combined P=3.95 × 10(-14)), although the association of SNP rs3782889 doesn't remain statistically significant after adjusting for SNP rs11066015 (proxy SNP with BRAP (r(2)=1)). But new possible CAD-associated variant was observed for rs9508025 (FLT1), even though its statistical significance did marginally reach at the genome-wide a significance level (combined P=6.07 × 10(-7)). This study shows that three CAD susceptibility loci, which were previously identified in European can be directly replicated in Koreans and also provides additional evidences implicating suggestive loci as risk variants for CAD in East Asian.
PubMed IF 2.3 순환기내과
11842013

제1저자 박진주 · 교신저자 연태진

, , , , , , , , ,
Prognostic value of neutrophil to lymphocyte ratio in patients presenting with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.
Am J Cardiol. 2013;111(5):636-42.

Abstract
Atherosclerosis is an inflammatory process, and inflammatory biomarkers have been identified as useful predictors of clinical outcomes. The prognostic value of leukocyte count in patients with ST-segment elevation myocardial infarctions who undergo primary percutaneous coronary intervention is not clearly defined. In 325 patients with STEMIs treated with primary percutaneous coronary intervention, total and differential leukocyte counts, once at admission and 24 hours thereafter, were measured. The neutrophil/lymphocyte ratio (NLR) was calculated as the ratio of neutrophil count to lymphocyte count. The primary end point was all-cause death. Twenty-five patients (7.7%) died during follow-up (median 1,092 days, interquartile range 632 to 1,464). The total leukocyte count decreased (from 11,853 ± 3,946/μl to 11,245 ± 3,979/μl, p = 0.004) from baseline to 24 hours after admission. Patients who died had higher neutrophil counts (9,887 ± 5,417/μl vs 8,399 ± 3,639/μl, p = 0.061), lower lymphocyte counts (1,566 ± 786/μl vs 1,899 ± 770/μl, p = 0.039), and higher NLRs (8.58 ± 7.41 vs 5.51 ± 4.20, p = 0.001) at 24 hours after admission. Baseline leukocyte profile was not associated with outcomes. The best cut-off value of 24-hour NLR to predict mortality was 5.44 (area under the curve 0.72, 95% confidence interval [CI] 0.52 to 0.82). In multivariate analysis, a 24-hour NLR ≥5.44 was an independent predictor of mortality (hazard ratio 3.12, 95% CI 1.14 to 8.55), along with chronic kidney disease (hazard ratio 4.23, 95% CI 1.62 to 11.1) and the left ventricular ejection fraction (hazard ratio 0.94 for a 3% increase, 95% CI 0.76 to 0.93). In conclusion, NLR at 24 hours after admission can be used for risk stratification in patients with STEMIs who undergo primary PCI. Patients with STEMIs with 24-hour NLRs ≥5.44 are at increased risk for mortality and should receive more intensive treatment.
PubMed IF 2.5 순환기내과
11832013

제1저자 이은영 · 교신저자 송영욱

, ,
The interaction between CXCL10 and cytokines in chronic inflammatory arthritis.
Autoimmun Rev. 2013;12(5):554-7.

Abstract
There are several chemokines and their receptors involved in the pathogenesis of chronic inflammatory arthritis. Of those, CXCL10 and its receptor, CXCR3, are increased in many kinds of chronic inflammatory arthritis, especially in rheumatoid arthritis (RA). CXCL10 and CXCR3 play important roles in leukocyte homing to inflamed tissues and in the perpetuation of inflammation, and therefore, tissue damage. In addition to its chemotactic effect, CXCL10 may have pleiotropic functions. Our recent studies show that the crosstalk between CXCL10 and receptor activator of NF-κB ligand (RANKL) in inflamed synovial tissue may induce and perpetuate bone destruction in RA. The interaction between CXCL10 and tumor necrosis factor-α (TNF-α) can also contribute to sustained inflammation in RA. One human trial with anti-CXCL10 monoclonal antibody showed therapeutic potential of blocking CXCL10 in RA treatment. Understanding the novel interaction between this chemokine and other chemokines or cytokines may add possible therapeutic applications in inflammatory arthritis.
PubMed IF 9.8 류마티스내과
11822013

제1저자 안지현 · 교신저자 신찬수

, , , , , , , , , , , , , ,
Transplantation of human umbilical cord blood-derived mesenchymal stem cells or their conditioned medium prevents bone loss in ovariectomized nude mice.
Tissue Eng Part A. 2013;19(5-6):685-96.

Abstract
Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs.
PubMed IF 2.8 내분비대사내과
11812013

제1저자 백우현, 이상협 · 교신저자 류지곤

, , , , , ,
Long-term clinical outcomes of biliary cast syndrome in liver transplant recipients.
Liver Transpl. 2013;19(3):275-82.

Abstract
Biliary cast syndrome (BCS) is an uncommon complication of orthotopic liver transplantation (OLT), so the long-term treatment outcomes of BCS are not well characterized. The purpose of this study was to evaluate the long-term treatment outcomes and prognosis of BCS after OLT. The medical records of 1097 patients who underwent OLT from January 2000 to September 2009 were reviewed. Those patients who had BCS were evaluated with respect to the treatment method, overall survival and relapse rates, and relapse-free time. Twenty-three patients (2.1%) were diagnosed with BCS with a mean overall follow-up of 59.9 months. All the patients had benign biliary strictures and repeatedly underwent balloon dilatation by an endoscopic or percutaneous approach. Primary biliary cast removal was tried with the endoscopic method from 11 patients and with the percutaneous methods from 12 patients. Casts were completely removed by repetitive procedures in 22 patients, but BCS relapsed in 12 patients (55%). Persistent biliary strictures were significantly associated with the BCS relapse frequency (0.37 versus 0.05 times per year, P = 0.006). The 5-year overall survival rate for BCS patients after OLT was 87%. The risk factors associated with early relapse were female sex, hepatic artery stenosis, and acute cellular rejection. In a multivariate analysis, acute cellular rejection was the only significant risk factor for early relapse (hazard ratio = 11.1, 95% confidence interval = 1.9-63.2, P = 0.007). In conclusion, patients with BCS frequently relapse, and multiple interventions and the treatment of biliary strictures are needed. Acute cellular rejection after OLT is a significant risk factor for early relapse.
PubMed IF 3.8 소화기내과
11802013

제1저자 이주명, 임청 · 교신저자 연태진

, , , , , , , , ,
Candidates and major determinants for endovascular repair of abdominal aortic aneurysms in Korean patients.
Heart Vessels. 2013;28(2):215-21.

Abstract
The purpose of this study was to determine what proportion of patients with an abdominal aortic aneurysm (AAA) would be eligible for endovascular aneurysm repair (EVAR) and to examine the major determinants for suitability of EVAR with the currently available indications. We retrospectively reviewed 3-D reconstructed computed tomography angiography of 88 patients with an atherosclerotic AAA who underwent open repair or EVAR between October 2003 and October 2010 at the Cardiovascular Center, Seoul National University Bundang Hospital. Of the 88 patients, 71 (80.7%) were treated with open repair and 17 (19.3%) were treated with EVAR. The rate of minor complications, postprocedural intensive care unit stay, and total hospital stay were significantly lower in the EVAR group. When the suitability of EVAR was reevaluated using morphologic criteria, a total of 33 (37.5%) patients were considered eligible for EVAR. Multivariate analysis revealed that proximal neck length, proximal neck angle, and aneurismal sac size were independent determinants for suitability of EVAR. Taking into account the increased clinical experience and the availability of new devices, EVAR would be applicable in about 40% of atherosclerotic AAA cases in this series of Korean patients. Accurate identification of candidates for EVAR by detailed preoperative evaluation, especially for morphologic characteristics, is essential.
PubMed IF 1.5 순환기내과
11792013

제1저자 박효은 · 교신저자 오세일

, , , , ,
Left ventricular dyssynchrony in pre-excitation syndrome: effect of accessory pathway location and reversibility after ablation therapy.
Heart Vessels. 2013;28(2):199-207.

Abstract
We sought to evaluate the effects and reversibility of different locations of accessory pathways (AP) on left ventricular dyssynchrony (LVdys). The acute and chronic effects of AP were evaluated in a canine model (n = 11) and in patients with pre-excitation syndrome (n = 25). Pre-excitation was simulated in the canine model by applying VDD-type epicardial ventricular pacing near the atrioventricular (AV) groove with 50-ms AV interval after median thoracotomy, at five different sites in each animal. For the simulation of pre-excitation through the septal accessory pathway, right basal septal pacing was performed using a transvenous lead. Left ventricular dyssynchrony was measured by a two-dimensional speckle-tracking technique: before and during pacing in the canine model, and before and within 24 h after the ablation in patients with Wolff-Parkinson-White (WPW) syndrome. In the canine model, the most prominent intraventricular LVdys was observed in left lateral pre-excitation (P < 0.001). In patients with pre-excitation syndrome, LVdys was greatest in patients with left free wall accessory pathways before the ablation (P = 0.013). After catheter ablation, such a difference diminished (P = 0.619). The degree of LVdys was different according to the site of AP in both the acute model and chronic patients, and the most significant LVdys associated with pre-excitation was observed in left lateral AP. Left ventricular dyssynchrony was reversible in patients with WPW syndrome. Left ventricular dyssynchrony observed in patients with pre-excitation syndrome might be a different entity from that observed in patients with heart failure.
PubMed IF 1.5 순환기내과
11782013

제1저자 이상민 · 교신저자 A.Murat Kaynar

, , , , , , , , , , , , , , , , , ,
Metallothionein-induced zinc partitioning exacerbates hyperoxic acute lung injury.
Am J Physiol Lung Cell Mol Physiol. 2013;304(5):L350-60.

Abstract
Hypozincemia, with hepatic zinc accumulation at the expense of other organs, occurs in infection, inflammation, and aseptic lung injury. Mechanisms underlying zinc partitioning or its impact on extrahepatic organs are unclear. Here we show that the major zinc-binding protein, metallothionein (MT), is critical for zinc transmigration from lung to liver during hyperoxia and preservation of intrapulmonary zinc during hyperoxia is associated with an injury-resistant phenotype in MT-null mice. Particularly, lung-to-liver zinc ratios decreased in wild-type (WT) and increased significantly in MT-null mice breathing 95% oxygen for 72 h. Compared with female adult WT mice, MT-null mice were significantly protected against hyperoxic lung injury indicated by reduced inflammation and interstitial edema, fewer necrotic changes to distal airway epithelium, and sustained lung function at 72 h hyperoxia. Lungs of MT-null mice showed decreased levels of immunoreactive LC3, an autophagy marker, compared with WT mice. Analysis of superoxide dismutase (SOD) activity in the lungs revealed similar levels of manganese-SOD activity between strains under normoxia and hyperoxia. Lung extracellular SOD activity decreased significantly in both strains at 72 h of hyperoxia, although there was no difference between strains. Copper-zinc-SOD activity was ~4× higher under normoxic conditions in MT-null compared with WT mice but was not affected in either group by hyperoxia. Collectively the data suggest that genetic deletion of MT-I/II in mice is associated with compensatory increase in copper-zinc-SOD activity, prevention of hyperoxia-induced zinc transmigration from lung to liver, and hyperoxia-resistant phenotype strongly associated with differences in zinc homeostasis during hyperoxic acute lung injury.
PubMed IF 3.8 호흡기내과
11772013

제1저자 허진, 최재일, 윤지연 · 교신저자 김효수

, , , , , , , , , , , , ,
Highly angiogenic CXCR4(+)CD31(+) monocyte subset derived from 3D culture of human peripheral blood.
Biomaterials. 2013;34(8):1929-41.

Abstract
Ex vivo expansion of human circulating angiogenic cells is a major challenge in autologous cell therapy for ischemic diseases. Here, we demonstrate that hematosphere-derived CXCR4(+)CD31(+) myeloid cells using peripheral blood possess robust proangiogenic capacity such as formation of vessel-like structures and tip cell-like morphology in Matrigel. We also found that CD31 positive myeloid cells are principal cellular component of hematospheres by magnetic cell sorting. Flow cytometry analysis showed that fresh peripheral blood contained 40.3 ± 15.2% of CXCR4(+)CD31(+) myeloid cells, but at day 5 of hematosphere culture, most of myeloid cells were CXCR4(+)CD31(+) by 86.9 ± 5.4%. Hematosphere culture significantly increased the production of angiogenic niche-supporting cytokines. Moreover, CD31-homophilic interaction and VEGF-VEGF receptor loop signaling were essential for sphere formation and acquisition of angiogenic capacity in hematospheres. Matrigel plug and ischemic hindlimb model provide in vivo evidence that hematosphere-derived myeloid cells have highly vasculogenic capacities, participate in new and mature vessel formation, and exert therapeutic effects on ischemic hindlimb. In conclusion, our strategy for ex vivo expansion of human CXCR4(+)CD31(+) angiogenic cells using hematospheres provides an autologous therapeutic cell source for ischemic diseases and a new model for investigating the microenvironment of angiogenesis.
PubMed IF 13.6 순환기내과
11762013

제1저자 안동원 · 교신저자 류지곤

, , , , , ,
Inflexinol reduces severity of acute pancreatitis by inhibiting nuclear factor-κB activation in cerulein-induced pancreatitis.
Pancreas. 2013;42(2):279-84.

Abstract
OBJECTIVES To examine the effect of inflexinol on the development of acute pancreatitis (AP) and to investigate the mechanisms responsible for the protective effect against AP.
METHODS Acute pancreatitis was induced in mice by intraperitoneal injection of cerulein. Inflexinol was administered intraperitoneally 4 times every 6 hours from 1 hour before the first cerulein injection. Serum amylase activity and histology of the pancreas were measured. Determination of pancreatic nuclear factor-κB (NF-κB) p65 expression was conducted by Western blotting and immunohistochemistry to investigate the mechanisms responsible for the inflexinol effects.
RESULTS Serum amylase activity in the cerulein group was significantly higher than that in the control group (P < 0.05). Pancreatic histology revealed marked inflammatory changes in the cerulein group such as interstitial edema, vacuolization, necrosis, and infiltration of inflammatory cells; and Western blotting and immunohistochemistry showed marked NF-κB p65 expression. Treatment with inflexinol significantly attenuated the inflammatory changes in pancreatic histology at 24, 48, and 72 hours (P < 0.05). Pancreatic NF-κB p65 expression decreased significantly after inflexinol treatment (P < 0.05).
CONCLUSION Inflexinol reduced the severity of cerulein-induced AP by inhibiting NF-κB activation.
PubMed IF 2.2 소화기내과
11752013

제1저자 임호영 · 교신저자 윤성수

, , , , , , , , , , , , , , , , , , ,
Matched-pair analysis to compare the outcomes of a second salvage auto-SCT to systemic chemotherapy alone in patients with multiple myeloma who relapsed after front-line auto-SCT.
Bone Marrow Transplant. 2013;48(3):425-32.

Abstract
The aims of this study were to investigate the outcomes of second salvage auto-SCT and to identify the impacts of a second auto-SCT compared with systemic chemotherapy alone on disease outcome. Data from 48 patients who underwent second auto-SCT were matched to 144 patients (1:3) who received systemic chemotherapy alone from the Korean Myeloma Registry. Groups were matched for nine potential prognostic factors and compared for treatment outcomes. The median age of matching-pairs at relapse was 55.5 years. A total of 156 patients (81%) received vincristine, doxorubicin and dexamethasone induction therapy before the first auto-SCT. Thirty-five patients (73%) in the second auto-SCT group received novel agent-based therapies before the second auto-SCT, and similar proportion in both groups received novel therapies after relapse of front-line auto-SCT. With a median follow-up of 55.3 months, patients who underwent a second auto-SCT had significantly better median OS (55.5 vs 25.4 months, P=0.035). In multivariate analysis for OS, <18 months time to progression after first auto-SCT, International Staging System III and salvage chemotherapy alone were independent predictors for worse OS. The outcomes of second auto-SCT appear to be superior to those of systemic chemotherapy alone. A randomized trial comparing both treatment strategies is required.
PubMed IF 5.1 혈액종양내과
11742013

제1저자 최홍윤 · 교신저자 팽진철, 김동완

, , , , , , ,
Metabolic and metastatic characteristics of ALK-rearranged lung adenocarcinoma on FDG PET/CT.
Lung Cancer. 2013;79(3):242-7.

Abstract
INTRODUCTION ALK rearrangement in lung cancer has been identified as a novel molecular target in lung adenocarcinoma. In this study, we evaluated metabolic and metastatic features of lung adenocarcinoma by using FDG PET/CT, with regard to specific genotypes of ALK and EGFR mutation.
METHODS Patients with lung adenocarcinoma initially diagnosed and examined with FDG PET/CT and molecular genotyping with biopsy specimen, from September 2009 to September 2011, were selected retrospectively. ALK fluorescence in situ hybridization and EGFR mutations were tested. Maximum standardized uptake value (SUVmax) and metastatic characteristics on FDG PET/CT were analyzed with regard to ALK and EGFR status.
RESULTS Of the 331 lung adenocarcinoma patients, 18 were ALK positive (ALK(+)), 156 were EGFR mutation positive (EGFR(+)), and 157 were wild type (WT) for both ALK and EGFR mutation. The ALK(+) tumor showed significantly higher SUVmax and more common metastasis to lymph nodes and distant organs than those of other genotypes in overall patients (P<0.01). In a subgroup analysis of advanced stage (stage IIIb and IV), ALK(+) lung cancer showed significantly higher SUVmax (P<0.05) than EGFR(+) tumors. In another subgroup analysis of size matched groups, ALK(+) tumors showed significant difference in SUVmax, lymph node and distant metastasis (P<0.01), particularly in the moderate-sized tumors (1.5-3cm).
CONCLUSION ALK-rearranged lung adenocarcinoma represents higher glucose metabolism and more rapid metastasis to lymph nodes or distant sites compared with those with EGFR mutation and wild type, which suggests more aggressive features of ALK rearrangement.
PubMed IF 5.3 혈액종양내과
11732013

제1저자 이연주 · 교신저자 임재준

, , , , , ,
Contamination rates between smart cell phones and non-smart cell phones of healthcare workers.
J Hosp Med. 2013;8(3):144-7.

Abstract
BACKGROUND Healthcare workers' mobile phones are easily contaminated with pathogenic bacteria and could be vehicles of transmission. Smart phones are increasingly used in the hospital. The objective of this study was to compare the contamination rate of bacteria with pathogenic potential between smart phones and non-smart phones.
METHODS We screened mobile phones of healthcare workers in three teaching hospitals in South Korea. The identification of cultivated micro-organisms and assessment of antibiotic susceptibility were performed.
RESULTS One hundred fifteen (56.7%) participants used smart phones, and 88 (43.3%) used non-smart phones. Bacteria with pathogenic potential were isolated from 58 (28.6%) mobile phones, more often from smart phones than from non-smart phones (34.8% vs 20.5%, P=0.03). Multivariate analysis including various characteristics to determine risk factors revealed that only smart phones (vs non-smart phones) were a significant risk factor for contamination by bacteria with pathogenic potential (adjusted odds ratio [OR], 4.02; 95% confidence interval [CI], 1.43-11.31). Also, in a multivariate model including phone size, the smart phone was still a significant risk factor for the pathogen contamination (OR, 4.17; 95% CI, 1.07-16.33; P=0.04).
CONCLUSION The smart phones of healthcare workers were contaminated with bacteria with pathogenic potential to a greater extent than were non-smart phones.
PubMed IF 1.8 호흡기내과
11722013

제1저자 임수 · 교신저자 장학철

, , , , , , ,
Association of vitamin D deficiency with incidence of type 2 diabetes in high-risk Asian subjects.
Am J Clin Nutr. 2013;97(3):524-30.

Abstract
BACKGROUND Recent studies suggest an association between 25-hydroxyvitamin D [25(OH)D] and type 2 diabetes (T2D) risk. However, prospective studies investigating the relation between vitamin D inadequacy and incidence of T2D incorporating obesity and dynamic measures of insulin resistance (IR) and pancreatic β cell function are limited.
OBJECTIVE We tested the hypothesis that baseline 25(OH)D is associated with the incidence of T2D in high-risk subjects for up to 5 y of follow-up, independently of obesity, baseline IR, and β cell function.
DESIGN We recruited 1080 nondiabetic Korean subjects [mean ± SD age: 49.5 ± 11.4 y] based on the presence of one or more risk factors for T2D, including obesity, hypertension, dyslipidemia, and/or family history of T2D. We measured anthropometric and biochemical indicators, HOMA2-IR, and the insulinogenic index (IGI; calculated as change in insulin at 30 min/change in glucose at 30 min) from a 75-g oral-glucose-tolerance test.
RESULTS Of the participants, 10.5% had a serum 25(OH)D deficiency (<10 ng/mL), 51.6% had an insufficiency (10.0-19.9 ng/mL), and 38.0% had a sufficiency (≥20 ng/mL), and the incidence of T2D at 32.3 ± 15.6 mo (±SD) declined accordingly: 15.9%, 10.2%, and 5.4%, respectively (P < 0.001). After adjustment for age, sex, blood pressure, lifestyles, family history, season, parathyroid hormone, and high-sensitivity C-reactive protein, the participants with 25(OH)D deficiency had an increased risk of T2D independently of BMI, HOMA2-IR, and IGI; the HRs were 2.06 (95% CI: 1.22, 3.49) for 25(OH)D 10-19.9 ng/mL compared with ≥20 ng/mL and 3.23 (95% CI: 1.66, 6.30) for 25(OH)D <10 ng/mL compared with ≥20 ng/mL.
CONCLUSION The current prospective study suggests that vitamin D metabolism may play a role in T2D pathogenesis independently of known risk factors. This trial was registered at clinicaltrials.gov as NCT01508481.
PubMed IF 6.9 내분비대사내과
11712013

제1저자 문재훈 · 교신저자 정준기, 박도준

, , , , , , , , , , , ,
Thyroglobulin in washout fluid from lymph node fine-needle aspiration biopsy in papillary thyroid cancer: large-scale validation of the cutoff value to determine malignancy and evaluation of discrepant results.
J Clin Endocrinol Metab. 2013;98(3):1061-8.

Abstract
CONTEXT There are still some controversies regarding the cutoff value and the influential factors of thyroglobulin (Tg) concentration in washout fluid from fine-needle aspiration (FNA) biopsy (FNA-Tg) on cervical lymph nodes (LNs) in patients with papillary thyroid cancer (PTC).
OBJECTIVE Our aims were to validate the cutoff value of FNA-Tg in diagnosing malignant LNs on a large scale and to investigate the influential factors that could result in the discrepancy between the final diagnosis and FNA-Tg.
DESIGN, SETTING, AND PARTICIPANTS We conducted a retrospective cohort study based on hospital records with 528 cases of FNA-Tg measurement from 419 PTC patients.
MAIN OUTCOME MEASURE The cutoff value of FNA-Tg was obtained from receiver operating characteristic analysis with final diagnosis. Binary logistic regression analysis was performed to investigate the influential factors.
RESULTS In the final diagnosis, 190 LNs were malignant, and 338 LNs were benign. The median FNA-Tg was 521.2 (3676.8) ng/mL in malignant LNs, and 0.1 (0.2) ng/mL in benign LNs. The optimal cutoff value of FNA-Tg in distinguishing malignant LNs from benign LNs was 1.0 ng/mL (sensitivity, 93.2%; specificity, 95.9%) in all cases. Combining FNA-Tg and FNA cytology showed superior diagnostic power (sensitivity, 98.4%; specificity, 94.4%) when compared with diagnostic strategy using either FNA cytology or FNA-Tg alone. FNA-Tg, serum TSH, and serum Tg were higher in nonthyroidectomized patients than in thyroidectomized patients (P < .001, respectively). FNA-Tg was correlated with serum TSH and Tg levels (P < .001, respectively), and binary logistic regression analysis showed that serum TSH suppression and serum Tg presence independently affected the diagnosis made by FNA-Tg.
CONCLUSIONS Our results validated 1.0 ng/mL of FNA-Tg as a cutoff value for diagnosing LN metastasis of PTC and suggested that serum TSH suppression and serum Tg presence should be considered in diagnosing LN malignancy with FNA-Tg in PTC patients.
PubMed IF 5.4 내분비대사내과
11702013

제1저자 박정환 · 교신저자 진호준

, , , , , , ,
Decreased estimated glomerular filtration rate is not directly related to increased insulin resistance.
Diabetes Res Clin Pract. 2013;99(3):366-71.

Abstract
AIMS Insulin resistance (IR) is associated with chronic kidney disease (CKD) but little is known about the possible causal relationship and differences in IR based on estimated glomerular filtration rate (eGFR) groups. The objective of this study was to identify a possible association between the level of renal dysfunction and IR.
METHODS We measured eGFR and calculated the Homeostasis Model Assessment IR (HOMA-IR) index value. The study included 17,157 subjects ≥20years old without diabetes who underwent voluntary health check-ups. We classified subjects into four groups according to eGFR: Group 1, eGFR ≥90; Group 2, eGFR 75-89; Group 3, eGFR 60-74; Group 4, eGFR <60mL/min/1.73m(2).
RESULTS While HOMA-IR index values were higher in lower eGFR groups compared with higher eGFR groups (P<0.001), multivariate analysis revealed that the relationship was not significant. HOMA-IR index values in eGFR groups estimated by analysis of covariance (ANCOVA) adjusted for related factors were not significantly higher in lower eGFR groups. When we stratified the subjects by the number of MS components, there were no meaningful differences in HOMA-IR values according to eGFR group. The frequency of high HOMA-IR index (≥2.5) among eGFR groups stratified with number of MS components was not significantly different.
CONCLUSION Decreased kidney function is not associated with IR.
PubMed IF 4.6 신장내과
11692013

제1저자 양재연 · 교신저자 신찬수

, , , , , , ,
Osteoblast-targeted overexpression of TAZ increases bone mass in vivo.
PLoS One. 2013;8(2):e56585.

Abstract
Osteoblasts are derived from mesenchymal progenitors. Differentiation to osteoblasts and adipocytes is reciprocally regulated. Transcriptional coactivator with a PDZ-binding motif (TAZ) is a transcriptional coactivator that induces differentiation of mesenchymal cells into osteoblasts while blocking differentiation into adipocytes. To investigate the role of TAZ on bone metabolism in vivo, we generated transgenic mice that overexpress TAZ under the control of the procollagen type 1 promoter (Col1-TAZ). Whole body bone mineral density (BMD) of 6- to 19-week-old Col-TAZ mice was 4% to 7% higher than that of their wild-type (WT) littermates, whereas no difference was noticed in Col.1-TAZ female mice. Microcomputed tomography analyses of proximal tibiae at 16 weeks of age demonstrated a significant increase in trabecular bone volume (26.7%) and trabecular number (26.6%) with a reciprocal decrease in trabecular spacing (14.2%) in Col1-TAZ mice compared with their WT littermates. In addition, dynamic histomorphometric analysis of the lumbar spine revealed increased mineral apposition rate (42.8%) and the serum P1NP level was also significantly increased (53%) in Col.1-TAZ mice. When primary calvaria cells were cultured in osteogenic medium, alkaline phosphatase (ALP) activity was significantly increased and adipogenesis was significantly suppressed in Col1-TAZ mice compared with their WT littermates. Quantitative real-time polymerase chain reaction analyses showed that expression of collagen type 1, bone sialoprotein, osteocalcin, ALP, osterix, and Runx2 was significantly increased in calvaria cells from Col1-TAZ mice compared to their WT littermates. In vitro, TAZ enhanced Runx2-mediated transcriptional activity while suppressing the peroxisome proliferator-activated receptor gamma signaling pathway. TAZ also enhanced transcriptional activity from 3TP-Lux, which reflects transforming growth factor-beta (TGF-β)-mediated signaling. In addition, TAZ enhanced TGF-β-dependent nuclear translocation of Smad2/3 and Smad4. Taken together, these results suggest that TAZ positively regulates bone formation in vivo, which seems to be mediated by enhancing both Runx2 and TGF-β signaling.
PubMed IF 2.8 내분비대사내과

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.