SCI 발표논문

1. 2682007

   제1저자 주권욱 · 교신저자 한진석

   Joo KW, Lee JW, Jang HR, Heo NJ, Jeon US, Oh YK, Lim CS, Na KY, Kim J, Cheong HI, Han JS

   Reduced urinary excretion of thiazide-sensitive Na-Cl cotransporter in Gitelman syndrome: preliminary data.

   Am J Kidney Dis. 2007;50(5):765-73.

   Abstract

   BACKGROUND The relationship between SLC12A3 mutations and actual sodium-chloride (Na-Cl) cotransporter (NCC) expression in patients with Gitelman syndrome (GS) was rarely evaluated. Detection of urinary thiazide-sensitive NCC was not tried in patients with GS.

   STUDY DESIGN Case series.

   SETTING & PARTICIPANTS 6 patients with GS and 1 patient with surreptitious vomiting.

   OUTCOMES & MEASUREMENTS Renal clearance study, mutation analysis using reverse-transcription polymerase chain reaction and direct sequencing for the SLC12A3 gene, and immunohistochemical staining for NCC, Na-K-2Cl-cotransporter, alpha1-subunit of Na(+),K(+)-ATPase, and calbindin-D(28K) of the renal biopsy specimens were performed. Membrane fractions of urine were obtained by using differential centrifugation and probed with antibodies against human NCC and aquaporin 2.

   RESULTS Results of clearance studies were consistent with GS, showing decreased distal fractional chloride reabsorption with only furosemide. SLC12A3 gene mutations were found in all patients with GS. Immunohistochemistry showed markedly decreased NCC expression in the distal convoluted tubule, whereas expression of other transporters remained intact. Urinary NCC excretion was markedly decreased in patients with GS, but not in the patient with surreptitious vomiting.

   LIMITATIONS Small number of patients and lack of mutation analysis of CLCNKB.

   CONCLUSIONS There were no relations between NCC expression and types of mutations. Detection of urinary NCC might be helpful for the differential diagnosis of GS.

   PubMed IF 9.4 신장내과
2. 2672007

   제1저자 "김의석, 송진수" · 교신저자 김홍빈

   Kim ES, Song JS, Lee HJ, Choe PG, Park KH, Cho JH, Park WB, Kim SH, Bang JH, Kim DM, Park KU, Shin S, Lee MS, Choi HJ, Kim NJ, Kim EC, Oh MD, Kim HB, Choe KW

   A survey of community-associated methicillin-resistant Staphylococcus aureus in Korea.

   J Antimicrob Chemother. 2007;60(5):1108-14.

   Abstract

   OBJECTIVES Methicillin-resistant Staphylococcus aureus (MRSA), originally restricted to hospitals, has emerged as a significant pathogen in the community. Although MRSA accounts for over 60% of S. aureus in tertiary hospitals in Korea, little is known about the epidemiology of community-associated MRSA (CA-MRSA).

   METHODS From January to July 2005, a hospital laboratory-based survey was conducted in seven community-based or tertiary hospitals. The medical records and Health Insurance Review Agency databases were reviewed and MRSA isolated from patients without apparent risk factors was defined as CA-MRSA. Susceptibilities to 12 antibiotics were tested by the disc diffusion method. SCCmec typing, Panton-Valentine leucocidin (PVL) gene detection and multilocus sequence typing (MLST) were performed according to published protocols.

   RESULTS Of 3,251 S. aureus, 1,900 (58.4%) were MRSA. CA-MRSA accounted for 112 (5.9%) of the MRSA. Of the 112 CA-MRSA isolates, 27 and 33 were found to be pathogens and colonizers, respectively. Fifty-two isolates from the patients with chronic otitis media were classified as 'undetermined'. Most of the 27 CA-MRSA patients had skin and soft tissue infections or acute ear infections. None of the patients died during the study period. Among 72 isolates tested, 64% were multidrug-resistant. SCCmec type IVa was the most common type among the colonizers and pathogens. On MLST analysis, ST72 was predominant, but ST5 and ST239 were prevalent in the 'undetermined' group. None possessed the PVL gene.

   CONCLUSIONS Despite MRSA-endemic hospital settings, CA-MRSA infections are not common in Korea. A new clone of CA-MRSA, ST72-SCCmec type IVa without the PVL gene, is the most common form.

   PubMed IF 3.6 감염내과
3. 2662007

   제1저자 김범석 · 교신저자 임석아

   Keam B, Im SA, Kim HJ, Oh DY, Kim JH, Lee SH, Chie EK, Han W, Kim DW, Moon WK, Kim TY, Park IA, Noh DY, Heo DS, Ha SW, Bang YJ

   Prognostic impact of clinicopathologic parameters in stage II/III breast cancer treated with neoadjuvant docetaxel and doxorubicin chemotherapy: paradoxical features of the triple negative breast cancer.

   BMC Cancer. 2007;7:203.

   Abstract

   BACKGROUND Prognostic factors in locally advanced breast cancer treated with neoadjuvant chemotherapy differ from those of early breast cancer. The purpose of this study was to identify the clinical significance of potential predictive and prognostic factors in breast cancer patients treated by neoadjuvant chemotherapy.

   METHODS A total of 145 stage II and III breast cancer patients received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. We examined the clinical and biological factors (ER, PR, p53, c-erbB2, bcl-2, and Ki-67) by immunohistochemistry. We analyzed clinical outcome and their correlation with clinicopathologic parameters.

   RESULTS Among the clinicopathologic parameters investigated, none of the marker was correlated with response rate (RR) except triple negative phenotype. Patients with triple negative phenotype showed higher RR (83.0% in triple negative vs. 62.2% in non-triple negative, p = 0.012) and pathologic complete RR (17.0% in triple negative vs. 3.1% in non-triple negative, p = 0.005). However, relapse free survival (RFS) and overall survival (OS) were significantly shorter in triple negative breast cancer patients (p < 0.001, p = 0.021, respectively). Low histologic grade, positive hormone receptors, positive bcl-2 and low level of Ki-67 were associated with prolonged RFS. In addition, positive ER and positive bcl-2 were associated with prolonged OS. In our homogeneous patient population, initial clinical stage reflects RFS and OS more precisely than pathologic stage. In multivariate analysis, initial clinical stage was the only significant independent prognostic factor to impact on OS (hazard ratio 3.597, p = 0.044).

   CONCLUSION Several molecular markers provided useful predictive and prognostic information in stage II and III breast cancer patients treated with neoadjuvant docetaxel/doxorubicin chemotherapy. Triple negative phenotype was associated with shorter survival, even though it was associated with a higher response rate to neoadjuvant chemotherapy.

   PubMed IF 4.1 혈액종양내과
4. 2652007

   제1저자 김태유 · 교신저자 방영주

   Kim TY, Han SW, Bang YJ

   Chasing targets for EGFR tyrosine kinase inhibitors in non-small-cell lung cancer: Asian perspectives.

   Expert Rev Mol Diagn. 2007;7(6):821-36.

   Abstract

   EGF receptor (EGFR) activation has an important role in various steps of carcinogenesis and progression of non-small-cell lung cancer (NSCLC), implying that EGFR is a potential target for cancer therapy. Therefore, targeted treatments aimed at EGFR have been developed, of which tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib have shown activity in NSCLC. The unexpected findings of a lack of association between expression of EGFR, the target and efficacy of EGFR TKIs and higher response in selective subgroups of patients were puzzling. Identification of somatic activating mutations in the EGFR tyrosine kinase domain solved the mystery and provided new insight. Several lines of study provided information on various molecular targets for EGFR TKI therapy. A target-based patient-selection strategy is expected to eventually lead to tailored therapy for lung cancer.

   PubMed IF 4.3 혈액종양내과
5. 2642007

   제1저자 오병희 · 교신저자 오병희

   Oh BH

   Aliskiren, the first in a new class of direct renin inhibitors for hypertension: present and future perspectives.

   Expert Opin Pharmacother. 2007;8(16):2839-49.

   Abstract

   Aliskiren, the direct renin inhibitor, is the first new class of drug available in 13 years for the treatment of hypertension. Renin has long been recognized as a preferred site for blockade of the renin-angiotensin-aldosterone system because it prevents conversion of angiotensinogen to angiotensin I. Aliskiren binds to the active site of the renin molecule, blocking angiotensinogen cleavage, thus, preventing the formation of angiotensin I. Clinical studies have demonstrated at least equivalent or superior blood pressure lowering efficacy compared with existing drugs with a favorable side effect profile. Aliskiren possesses possible synergistic potential when combined with a thiazide diuretic, ACE inhibitor, angiotensin receptor blocker and calcium channel blocker both in terms of efficacy and tolerability. This review aims to define the role of aliskiren in the therapeutic management of hypertension.

   PubMed IF 3.4 순환기내과
6. 2632007

   제1저자 정용진 · 교신저자 이효석

   Jung YJ, Kim YJ, Kim LH, Lee SO, Park BL, Shin HD, Lee HS

   Putative association of Fas and FasL gene polymorphisms with clinical outcomes of hepatitis B virus infection.

   Intervirology. 2007;50(5):369-76.

   Abstract

   OBJECTIVE Fas/FasL polymorphisms, which are related to apoptosis, might influence the clearance of hepatitis B virus (HBV) infection and the occurrence of hepatocellular carcinoma (HCC). This study was performed to determine whether Fas and FasL promoter polymorphisms are associated with clinical outcome in chronic HBV infection.

   METHODS A total of 1,095 Korean subjects were prospectively allocated to two different groups: 'the chronic carrier group' (CC; n = 666), who were repeatedly hepatitis B surface antigen (HBsAg)-positive, and 'the spontaneous recovery group' (SR; n = 429), who were HBsAg-negative with antibodies to HBsAg and hepatitis B core antigen. In addition, the CC group was subcategorized into chronic hepatitis and HCC subgroups. Fas promoter polymorphisms at -1377G>A and -670A>G and the FasL promoter polymorphism at -844C>T were analyzed for and the genotype distributions of subjects were compared.

   RESULTS There were no significant associations between Fas or FasL promoter polymorphism with the HBV clearance and HBeAg clearance. However, -1377G>A in Fas promoter region showed protective effect to HCC occurrence (RH = 0.70, p = 0.03).

   CONCLUSIONS Fas-1377G>A polymorphisms might be involved in the pathogenesis of human HCC.

   PubMed IF 1.8 소화기내과
7. 2622007

   제1저자 허진 · 교신저자 김효수

   Hur J, Yang HM, Yoon CH, Lee CS, Park KW, Kim JH, Kim TY, Kim JY, Kang HJ, Chae IH, Oh BH, Park YB, Kim HS

   Identification of a novel role of T cells in postnatal vasculogenesis: characterization of endothelial progenitor cell colonies.

   Circulation. 2007;116(15):1671-82.

   Abstract

   BACKGROUND The colony number of early endothelial progenitor cells (EPCs) has been used as a quantitative indicator of the number of EPCs in the blood or as a biological marker of cardiovascular diseases. In the present study, we found a subset of T cells that were localized at the center of the EPC colony and played a pivotal role in colony formation and differentiation of early EPCs.

   METHODS AND RESULTS We found that CD3+ CD31+ CXCR4+ T cells (referred to as angiogenic T cells in the present study) constituted the center of EPC colonies during cultures of human peripheral blood mononuclear cells. These angiogenic T cells were required for colony formation and differentiation of early EPCs. They secreted high levels of angiogenic cytokines such as vascular endothelial growth factor, interleukin-8, and matrix metalloproteinases. Angiogenic T cells showed superior angiogenic potential to the other subset of T cells in the experiments with regard to Matrigel tube formation, adhesion, transendothelial migration, and collagen invasion assay, mainly through the stromal cell-derived factor 1/CXCR-4 axis. Furthermore, angiogenic T cells enhanced endothelial cell proliferation and function. In vivo study showed that angiogenic T cells play an important role in the process of vessel formation. Clinical study showed that the level of angiogenic T cells in the peripheral blood was well correlated with EPC colony numbers and had inverse relationships with age and the number of risk factors for coronary artery disease.

   CONCLUSIONS These findings suggest that angiogenic T cells could be a potential therapeutic target for ischemic cardiovascular diseases.

   PubMed IF 41.3 순환기내과
8. 2612007

   제1저자 김형관 · 교신저자 김용진

   Kim HK, Kim YJ, Shin JI, Hwang SJ, Jo SH, Park JS, Chang HJ, Sohn DW, Oh BH, Park YB, Choi YS

   Echocardiographic and hemodynamic findings in patients with mitral stenosis undergoing percutaneous mitral commissurotomy comparing those with chronic atrial fibrillation versus those with normal sinus rhythm.

   Am J Cardiol. 2007;100(7):1153-6.

   Abstract

   Chronic atrial fibrillation (AF) is common in patients with mitral stenosis (MS). Because AF induces electrical and mechanical remodeling of the left atrium, left atrial (LA) compliance is likely to be changed in its presence. This study was performed to investigate the influence of AF on LA compliance in patients with moderate to severe MS. Data were analyzed for 356 patients (282 women; mean age 40 +/- 11 years; range 17 to approximately 71) who were registered in the percutaneous mitral commissurotomy database. Mean LA pressure was lower (21 +/- 7 vs 26 +/- 8 mm Hg; p <0.001), but LA volume was higher in the AF than sinus-rhythm group (126 +/- 62 vs 74 +/- 27 ml; p <0.001), indicating higher LA compliance, which was further confirmed by lower LA v wave at catheterization in the AF group (27 +/- 9 for AF vs 32 +/- 10 mm Hg for sinus rhythm; p <0.001). In conclusion, the presence of AF has a significant influence on LA compliance in patients with moderate to severe MS.

   PubMed IF 2.5 순환기내과
9. 2602007

   제1저자 최병휘,유광하 · 교신저자 조상헌

   Choi BW, Yoo KH, Jeong JW, Yoon HJ, Kim SH, Park YM, Kim WK, Oh JW, Rha YH, Pyun BY, Chang SI, Moon HB, Kim YY, Cho SH

   Easy diagnosis of asthma: computer-assisted, symptom-based diagnosis.

   J Korean Med Sci. 2007;22(5):832-8.

   Abstract

   Diagnosis of asthma is often challenging in primary-care physicians due to lack of tools measuring airway obstruction and variability. Symptom-based diagnosis of asthma utilizing objective diagnostic parameters and appropriate software would be useful in clinical practice. A total of 302 adult patients with respiratory symptoms responded to a questionnaire regarding asthma symptoms and provoking factors. Questions were asked and recorded by physicians into a computer program. A definite diagnosis of asthma was made based on a positive response to methacholine bronchial provocation or bronchodilator response (BDR) testing. Multivariate logistic regression analysis was used to evaluate the significance of questionnaire responses in terms of discriminating asthmatics. Asthmatic patients showed higher total symptom scores than non-asthmatics (mean 5.93 vs. 4.93; p<0.01). Multivariate logistic regression analysis identified that response to questions concerning the following significantly discriminated asthmatics; wheezing with dyspnea, which is aggravated at night, and by exercise, cold air, and upper respiratory infection. Moreover, the presence of these symptoms was found to agree significantly with definite diagnosis of asthma (by kappa statistics). Receiver-operating characteristic curve analysis revealed that the diagnostic accuracy of symptom-based diagnosis was high with an area under the curve of 0.647 +/- 0.033. Using a computer-assisted symptom-based diagnosis program, it is possible to increase the accuracy of diagnosing asthma in general practice, when the facilities required to evaluate airway hyperresponsiveness or BDR are unavailable.

   PubMed IF 3.2 알레르기내과
10. 2592007

    제1저자 이유진 · 교신저자 박영주

    Lee YJ, Park DJ, Shin CS, Park KS, Kim SY, Lee HK, Park YJ, Cho BY

    Microarray analysis of thyroid stimulating hormone, insulin-like growth factor-1, and insulin-induced gene expression in FRTL-5 thyroid cells.

    J Korean Med Sci. 2007;22(5):883-90.

    Abstract

    To determine which genes are regulated by thyroid stimulating hormone (thyrotropin, TSH), insulin and insulin-like growth factor-1 (IGF-1) in the rat thyroid, we used the microarray technology and observed the changes in gene expression. The expressions of genes for bone morphogenetic protein 6, the glucagon receptor, and cyclin D1 were increased by both TSH and IGF-1; for cytochrome P450, 2c37, the expression was decreased by both. Genes for cholecystokinin, glucuronidase, beta, demethyl-Q 7, and cytochrome c oxidase, subunit VIIIa, were up-regulated; the genes for ribosomal protein L37 and ribosomal protein L4 were down-regulated by TSH and insulin. However, there was no gene observed to be regulated by all three: TSH, IGF-1, and insulin molecules studied. These findings suggest that TSH, IGF-1, and insulin stimulate different signal pathways, which can interact with one another to regulate the proliferation of thyrocytes, and thereby provide additional influence on the process of cellular proliferation.

    PubMed IF 3.2 내분비대사내과
11. 2582007

    제1저자 조남한 · 교신저자 임수

    Cho NH, Jang HC, Choi SH, Kim HR, Lee HK, Chan JC, Lim S

    Abnormal liver function test predicts type 2 diabetes: a community-based prospective study.

    Diabetes Care. 2007;30(10):2566-8.

    PubMed IF 22.6 내분비대사내과
12. 2572007

    제1저자 박주경 · 교신저자 류지곤

    Park JK, Ryu JK, Lee KH, Lee JK, Yoon WJ, Lee SH, Yoo JW, Woo SM, Lee GY, Lee CH, Kim YT, Yoon YB

    Quantitative analysis of NPTX2 hypermethylation is a promising molecular diagnostic marker for pancreatic cancer.

    Pancreas. 2007;35(3):e9-15.

    Abstract

    OBJECTIVES Percutaneous fine-needle aspiration cytology or biopsy has been used for pathological confirmation in pancreatic cancer. Sometimes, it is difficult to approach the mass because of surrounding major vessels, and there is a risk of seeding. Although endoscopic retrograde cholangiopancreatography (ERCP)-guided pancreatic duct brush cytology is less invasive, its reliability is very low. Recently, aberrantly methylated genes were reported in pancreatic cancer tissue. This study was to develop a novel molecular diagnostic approach based on epigenetic characteristics.

    METHODS We enrolled pathologically proven 33 pancreatic cancer patients and 22 benign pancreaticobiliary disease patients. The ERCP-guided pancreatic duct brush cytology samples were obtained. Genomic DNA was extracted, and NPTX2 CpG island hypermethylation was examined quantitatively by real-time polymerase chain reaction amplification after chemical modification.

    RESULTS Pancreatic cancer cytology samples had statistically significant higher levels of NPTX2 methylation compared with benign diseases, and the optimal cutoff value of NPTX2 methylation was 1.2%. The sensitivity was 87%, and specificity was 80%, whereas pathological examination by ERCP-guided pancreatic duct brush cytology had a sensitivity of 38%.

    CONCLUSIONS The quantitative analysis of NPTX2 hypermethylation may play a role in making highly sensitive and less invasive diagnosis of pancreatic cancer. Therefore, NPTX2 hypermethylation could be a promising molecular diagnostic marker.

    PubMed IF 2.2 소화기내과
13. 2562007

    제1저자 신형두 · 교신저자 이효석

    Shin HD, Park BL, Cheong HS, Yoon JH, Kim YJ, Lee HS

    SPP1 polymorphisms associated with HBV clearance and HCC occurrence.

    Int J Epidemiol. 2007;36(5):1001-8.

    Abstract

    BACKGROUND Secreted phosphoprotein-1 (SPP1) is a secreted arginine-glycine-aspartate (RGD)-containing phosphoprotein. SPP1 is overexpressed in metastatic hepatocellular carcinoma (HCC), and therefore could act as both a diagnostic marker and a potential therapeutic target for metastatic HCC. We investigated the genetic polymorphisms in SPP1 to determine whether it is a potential candidate gene for a host genetic study of hepatitis B virus (HBV) clearance and HCC occurrence.

    METHODS Five genetic variants in SPP1 were genotyped by TaqMan assay and the genetic association with HBV clearance and HCC occurrence was analysed.

    RESULTS Genetic association analysis of SPP1 polymorphisms with an HBV cohort (n = 1,069) from the Korean population revealed that the most common haplotype (SPP1-ht2 [T-T-C-T-A]) was associated with HBV clearance. The frequency of the SPP1-ht2-bearing genotype in the chronic carrier (CC) group was higher than in the spontaneously recovered (SR) group (OR = 1.44 [95% CI 1.11-1.87], P = 0.006, P(corr) = 0.02). By Cox relative hazard analysis, both SPP1-ht2 and -1,800G > T were associated with age of HCC occurrence among chronic hepatitis patients, e.g. ht2/h2- and 1800T/T-bearing patients showed earlier progression to HCC than did others (RH = 1.85, P = 0.004, P(corr) = 0.01 and RH = 1.85, P = 0.003, P(corr) = 0.01, respectively).

    CONCLUSION Our findings suggest that SPP1 polymorphisms might be among the genetic factors for HBV clearance and/or HCC occurrence.

    PubMed IF 5.7 소화기내과
14. 2552007

    제1저자 유병철 · 교신저자 이효석

    Yoo BC, Kim JH, Kim TH, Koh KC, Um SH, Kim YS, Lee KS, Han BH, Chon CY, Han JY, Ryu SH, Kim HC, Byun KS, Hwang SG, Kim BI, Cho M, Yoo K, Lee HJ, Hwang JS, Kim YS, Lee YS, Choi SK, Lee YJ, Yang JM, Park JW, Lee MS, Kim DG, Chung YH, Cho SH, Choi JY, Kweon YO, Lee HY, Jeong SH, Yoo HW, Lee HS

    Clevudine is highly efficacious in hepatitis B e antigen-negative chronic hepatitis B with durable off-therapy viral suppression.

    Hepatology. 2007;46(4):1041-8.

    Abstract

    UNLABELLED Clevudine is a pyrimidine analog with potent and sustained antiviral activity against HBV. In the present study, we evaluated the safety and efficacy of clevudine 30 mg daily for 24 weeks and assessed the durability of antiviral response for 24 weeks after cessation of dosing in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e-CHB). We randomized a total of 86 patients (3:1) to receive clevudine 30 mg (n = 63) or placebo (n = 23) daily for 24 weeks. We followed patients for an additional 24 weeks after withdrawal of treatment. The median changes in HBV DNA from baseline were -4.25 and -0.48 log(10) copies/mL at week 24 in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained after withdrawal of therapy, with 3.11 log(10) reduction at week 48. At week 24 and week 48, 92.1% and 16.4% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (<300 copies/mL). The proportion of patients who achieved ALT normalization was 74.6% and 33.3% in the clevudine and placebo groups at week 24, respectively (P = 0.0006). ALT normalization in the clevudine group was well-maintained during the post-treatment follow-up period. The incidence of adverse events was similar in the 2 groups. No resistance to clevudine was detected during treatment.

    CONCLUSION A 24-week clevudine therapy was well-tolerated and showed potent and sustained antiviral effect without evidence of viral resistance in e-CHB patients. However, treatment for longer than 24 weeks would be needed to achieve durable remission.

    PubMed IF 18 소화기내과
15. 2542007

    제1저자 이상협 · 교신저자 김용태

    Lee SH, Shin CM, Park JK, Woo SM, Yoo JW, Ryu JK, Yoon YB, Kim YT

    Outcomes of cystic lesions in the pancreas after extended follow-up.

    Dig Dis Sci. 2007;52(10):2653-9.

    Abstract

    Incidental pancreatic cysts are frequently detected, but no appropriate management guidelines have been issued for their management because their natural history is relatively unknown. The aim of this study was to investigate their long-term clinical outcomes. Pancreatic cysts detected from 1998 to 2004 were retrospectively reviewed in patients followed up for more than 3 months. A total of 182 patients with incidental pancreatic cysts (initial mean size, 1.8+/-1.1 cm) underwent follow-up for an average of 35.4 months. An age>/=60 years was found to be associated with an increase in cyst size, with an odds ratio of 2.56. Two malignant cysts were found among 20 patients who underwent surgical resection during follow-up. Old age was also associated with the presence of a premalignant or malignant cyst (P<0.01). Although the majority of incidental pancreatic cysts show an indolent behavior, long-term, regular follow-up studies should be considered for all pancreatic cysts, especially in the elderly.

    PubMed IF 2.8 소화기내과
16. 2532007

    제1저자 박완범 · 교신저자 김홍빈

    Park WB, Kim SH, Kang CI, Cho JH, Bang JW, Park KW, Lee YS, Kim NJ, Oh MD, Kim HB, Won Choe K

    In vitro ability of Staphylococcus aureus isolates from bacteraemic patients with and without metastatic complications to invade vascular endothelial cells.

    J Med Microbiol. 2007;56(Pt 10):1290-1295.

    Abstract

    Invasion of vascular endothelial cells is thought to be a critical step in the development of metastatic infections in patients with Staphylococcus aureus bacteraemia. This study was designed to evaluate the association between the ability to invade endothelial cells and metastatic infection by S. aureus. Patients with metastatic infection were identified among those with community-acquired S. aureus bacteraemia in a tertiary referral hospital. Patients with simple bacteraemia caused by S. aureus over the same period served as the control group. The ability of each clinical isolate to invade endothelial cells was evaluated by counting the number of intracellular organisms 1 h after inoculation onto human umbilical vein endothelial cells in vitro. The cytotoxic activity of intracellular S. aureus was determined 24 h after internalization, and expressed as the percentage of cells killed. The clinical isolates varied in invasiveness and cytotoxicity. The median invasiveness, relative to S. aureus reference strain ATCC 29213, was 145 % in the cases (n=10) [interquartile range (IQR) 103-160] and 153 % (IQR 111-173) in the controls (n=11; P=0.44). The median cytotoxicity was 59.4 % (IQR 47-68) in the cases and 65.2 % (IQR 50-74) in the controls (P=0.44). Differences in the ability of S. aureus to invade and destroy vascular endothelial cells in vitro were not associated with the development of metastatic complications in patients with S. aureus bacteraemia. This implies that the invasiveness and toxicity of S. aureus for endothelial cells may not be major determinants of metastatic infection.

    PubMed IF 2.7 감염내과
17. 2522007

    제1저자 배현미 · 교신저자 김동완

    Bae HM, Min HS, Lee SH, Kim DW, Chung DH, Lee JS, Kim YW, Heo DS

    Palliative chemotherapy for pulmonary pleomorphic carcinoma.

    Lung Cancer. 2007;58(1):112-5.

    Abstract

    Pulmonary pleomorphic carcinoma is a rare tumor of the lung, which is believed to spread at an early stage and to have an aggressive clinical course. The efficacy of chemotherapy for advanced pulmonary pleomorphic carcinoma has not been defined. The objective of this study was to evaluate the efficacy of palliative chemotherapy for pulmonary pleomorphic carcinoma. Thirteen consecutive patients who received palliative chemotherapy for advanced pulmonary pleomorphic carcinoma were investigated. All 13 patients were treated using chemotherapy regimens known to be active for the treatment of advanced non-small cell lung cancer (NSCLC). Eleven patients (85%) had progressive disease and two (15%) had stable disease after first-line chemotherapy. No patient achieved an objective response (objective response rate, 0%; 95% confidence interval, 0-23%). Of the 13, eight were given second-line chemotherapy, and all had progressive disease after second-line chemotherapy (objective response rate, 0%; 95% CI, 0-32%). Median overall survival from the initiation of first-line palliative chemotherapy was only 5 months (range, 2-12) with a median follow-up of 16 months. Advanced pulmonary pleomorphic carcinoma showed poor response to chemotherapy regimens that provide active treatment for NSCLC. Novel treatment approaches are required for pulmonary pleomorphic carcinoma.

    PubMed IF 5.3 혈액종양내과
18. 2512007

    제1저자 정연주 · 교신저자 김태유

    Jung Y, Park J, Kim TY, Park JH, Jong HS, Im SA, Robertson KD, Bang YJ, Kim TY

    Potential advantages of DNA methyltransferase 1 (DNMT1)-targeted inhibition for cancer therapy.

    J Mol Med (Berl). 2007;85(10):1137-48.

    Abstract

    The deoxyribonucleic acid (DNA) methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (5-aza-dC) has been used as a drug in a part of cancer therapy. However, because of its incorporation into DNA during DNA synthesis, 5-aza-dC can cause DNA damage, mutagenesis, and cytotoxicity. In view of the adverse effects of 5-aza-dC, DNMT-targeted inhibition may be a more effective approach than treatment with 5-aza-dC. To address the possibility of DNMT-targeted cancer therapy, we compared the effects of treatment with small interfering ribonucleic acids (siRNAs) specific for DNMT1 or DNMT3b and treatment with 5-aza-dC on transcription, cell growth, and DNA damage in gastric cancer cells. We found that DNMT1-targeted inhibition induced the re-expression and reversed DNA methylation of five (CDKN2A, RASSF1A, HTLF, RUNX3, and AKAP12B) out of seven genes examined, and 5-aza-dC reactivated and demethylated all seven genes. In contrast, DNMT3b siRNAs did not show any effect. Furthermore, the double knockdown of DNMT1 and DNMT3b did not show a synergistic effect on gene re-expression and demethylation. In addition, DNMT1 siRNAs showed an inhibitory effect of cell proliferation in the cancer cells and the induction of cell death without evidence of DNA damage, whereas treatment with 5-aza-dC caused DNA damage as demonstrated by the comet assay. These results provide a rationale for the development of a DNMT1-targeted strategy as an effective epigenetic cancer therapy.

    PubMed IF 5 혈액종양내과
19. 2502007

    제1저자 양종인 · 교신저자 윤정환

    Yang JI, Yoon JH, Myung SJ, Gwak GY, Kim W, Chung GE, Lee SH, Lee SM, Kim CY, Lee HS

    Bile acid-induced TGR5-dependent c-Jun-N terminal kinase activation leads to enhanced caspase 8 activation in hepatocytes.

    Biochem Biophys Res Commun. 2007;361(1):156-61.

    Abstract

    TGR5 is a novel G protein-coupled cell-surface bile acid receptor. In cholestasis, bile acids induce hepatocyte apoptosis by primarily activating death receptor-mediated signaling. We examined if bile acid-induced TGR5 activation is participating in bile acid-induced hepatocyte apoptosis. TGR5 expression and its responsiveness to bile acid were confirmed in human hepatocytes. TGR5 inhibition attenuated bile acid-induced caspase 8 activation, which resulted from reduced bile acid-induced caspase 8 recruited to a death-inducing signaling complex (DISC). Bile acid-induced c-Jun-N terminal kinase (JNK) activation was dependent on bile acid activation of TGR5. JNK formed complexes with caspase 8, which were reduced following bile acid treatment, but this reduction was prevented when TGR5 or JNK was inhibited. In conclusion, bile acids activate TGR5, which leads to JNK activation and reduced complex formation of JNK with caspase 8, thus facilitating caspase 8 recruitment to DISC. These observations suggest therapeutic applications for TGR5 signaling blockage in cholestasis.

    PubMed IF 2.5 소화기내과
20. 2492007

    제1저자 진상만 · 교신저자 이상민

    Jin SM, Choi SH, Yoo CG, Kim YW, Han SK, Shim YS, Lee SM

    Small solid noncalcified pulmonary nodules detected by screening chest computed tomography.

    Respir Med. 2007;101(9):1880-4.

    Abstract

    We aimed to determine the outcome of small (<10 mm) solid noncalcified pulmonary nodules detected by chest computed tomography (CT) scans. Reports of low-dose chest CT scans performed from October 2003 to April 2005 at the Seoul National University Hospital Healthcare System Gangnam Center were reviewed to identify patients with solid noncalcified pulmonary nodules smaller than 10 mm. Partly solid and nonsolid nodules or nodules without follow-up imaging within 1 year were excluded. Records were studied to determine if the initial nodules had changed in size. A total of 3478 chest CT examinations were performed, with 232 patients having small noncalcified nodules (6.7%). One hundred and thirty-eight patients met the criteria (104 men and 34 women) and 213 nodules were identified. The median age was 54 years (range 32-80) and at least 86 patients (62%) were at low to intermediate risk for developing lung cancer. The largest nodule was less than 5 mm in diameter in 87 patients (63%) and 5 mm or more in 51 patients (37%). None of the nodules grew and 29 (14%) decreased in size at follow-up CT scans performed within 12 months. When those individuals at low to intermediate risk for lung cancer were included, solid noncalcified subcentimeter nodules were less frequently found in low-dose CT screening and were nearly unchanged in size when a follow-up CT scan was done within 12 months.

    PubMed IF 3.3 호흡기내과
21. 2482007

    제1저자 엄상원 · 교신저자 이재호

    Um SW, Lee SW, Kwon SY, Yoon HI, Park KU, Song J, Lee CT, Lee JH

    Low serum concentrations of anti-tuberculosis drugs and determinants of their serum levels.

    Int J Tuberc Lung Dis. 2007;11(9):972-8.

    Abstract

    SETTING Low serum concentrations of anti-tuberculosis drugs have occasionally been associated with treatment failure.

    OBJECTIVE To determine the prevalence of low serum concentrations of anti-tuberculosis drugs and to identify the determinants of drug concentrations.

    DESIGN Venous blood was obtained 2 h after drug ingestion, and serum levels of isoniazid (INH), rifampicin (RMP), ethambutol (EMB), pyrazinamide (PZA), acetyl INH and 25-desacetyl RMP were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Patients with human immunodeficiency virus co-infection and gastrointestinal disease or diarrhoea were excluded.

    RESULTS Among 69 enrolled TB patients, the prevalence of a low 2 h serum concentration of at least one anti-tuberculosis drug was 46.4%. Prevalences of a low concentration of INH, RMP, EMB or PZA were 15.2%, 23.5%, 22.4% and 4.5%, respectively. By multivariate linear regression analysis, the serum concentrations of INH, RMP and PZA were positively associated with dose per kg of body weight (P < 0.05). Moreover, INH concentration was associated with acetyl INH/INH ratio (beta = -8.588, P < 0.001) and EMB concentration was associated with calculated creatinine clearance (beta = -0.025, P < 0.001).

    CONCLUSION Low concentrations of anti-tuberculosis drugs are common, and although the clinical significance of low concentrations remains uncertain, it may be necessary to optimise drug doses by therapeutic drug monitoring, especially in patients with an inadequate clinical response to chemotherapy.

    PubMed IF 3.6 호흡기내과
22. 2472007

    제1저자 양승희 · 교신저자 김연수

    Yang SH, Jin JZ, Lee SH, Park H, Kim CH, Lee DS, Kim S, Chung NH, Kim YS

    Role of NKT cells in allogeneic islet graft survival.

    Clin Immunol. 2007;124(3):258-66.

    Abstract

    Although NKT cells expressing CD1d-reactive TCR exerted protective role in autoimmune diseases, the regulatory function of CD1d-dependent NKT cells in alloimmune responses has not been investigated thoroughly. Here, we demonstrated the regulatory effects of NKT cells using a pancreas islet transplantation model. CD40/CD154 blocking induced long-term graft survival in most B6 recipients, but B6.CD1d(-/-) recipients showed co-stimulation blockade-resistant rejection. Adoptive transfer of NKT cells into B6.CD1d(-/-) restored tolerizing capacity of co-stimulatory blockade. Activation of NKT cells was effective for the prolongation of graft survival and up-regulated membrane-bound TGF-beta expression transiently on their cell surface. The activated CD1d-dependent NKT cells inhibited alloantigen-driven cell proliferation through cell contacts and the beneficial effect of CD154 blocking for allograft survival was related to TGF-beta pathway. Thus, we can conclude that NKT cells are essential for the stable allograft survival and the regulatory function is dependent on, at least in part, TGF-beta engagement.

    PubMed IF 4.1 신장내과
23. 2462007

    제1저자 강영애 · 교신저자 임재준

    Kang YA, Lee HW, Hwang SS, Um SW, Han SK, Shim YS, Yim JJ

    Usefulness of whole-blood interferon-gamma assay and interferon-gamma enzyme-linked immunospot assay in the diagnosis of active pulmonary tuberculosis.

    Chest. 2007;132(3):959-65.

    Abstract

    PURPOSES The aim of this study was to evaluate the usefulness of the whole-blood interferon-gamma assay (enzyme-linked immunosorbent assay [ELISA]) and interferon-gamma enzyme-linked immunospot assay (ELISPOT) based on early secretory antigenic target 6 and culture filtrate protein 10 in the diagnosis of active pulmonary tuberculosis (TB) in routine clinical practice.

    METHOD We conducted a prospective study enrolling 144 participants with suspected pulmonary TB in a tertiary referral hospital in Seoul, South Korea, to investigate the diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these tests. Clinical assessment, tuberculin skin test (TST), whole-blood interferon-gamma ELISA (QuantiFERON-TB Gold [QFT-G]; Cellestis Ltd; Victoria, Australia), and an ELISPOT assay (T SPOT.TB; Oxford Immunotec; Oxford, UK) were performed. Test results were compared with the final confirmed diagnoses.

    RESULTS Active pulmonary TB was diagnosed in 67 of 144 participants (47%). Sensitivities of QFT-G and T SPOT.TB for active pulmonary TB were 89% (95% confidence interval [CI], 79 to 96%) and 92% (95% CI, 83 to 97%), respectively; and specificities were 49% (95% CI, 37 to 61%) and 47% (95% CI, 36 to 59%). NPVs of QFT-G (84%; 95% CI, 69 to 93%) and T SPOT.TB (87%; 95% CI, 73 to 96%) were higher than that of TST (64%; 95% CI, 51 to 76%) [p = 0.001 and p < 0.001, respectively].

    CONCLUSION High NPVs of QFT-G and T SPOT.TB for the diagnosis of active TB suggest the supplementary role of these tests for the diagnostic exclusion of active TB, although the low PPV limits their usefulness in routine clinical practice in South Korea, where the prevalence of latent TB infection is considerable.

    PubMed IF 9.8 호흡기내과
24. 2452007

    제1저자 김용진 · 교신저자 Takahiro Shiota

    Kim YJ, Jones M, Greenberg NL, Popovic ZB, Sitges M, Bauer F, Thomas JD, Shiota T

    Evaluation of left ventricular contractile function using noninvasively determined single-beat end-systolic elastance in mitral regurgitation: experimental validation and clinical application.

    J Am Soc Echocardiogr. 2007;20(9):1086-92.

    Abstract

    OBJECTIVE We performed this study to validate the single-beat estimation of end-systolic elastance (E(es)) in an animal model of chronic mitral regurgitation (MR) and to use E(es) to predict postoperative left ventricular (LV) systolic function with the noninvasively derived single-beat E(es) (E(es-s)) in patients with MR.

    METHODS Eight sheep with MR were studied under 4 different loading conditions. E(es) was measured as the slope of the end-systolic pressure-volume relationship with a conductance catheter during inferior vena cava occlusion. E(es-s) was calculated using a bilinearly approximated time-varying elastance curve. We also studied 105 patients with MR who had undergone mitral valve repair. All measurements in these patients were performed before surgery and repeated at about 1 week after surgery.

    RESULTS In the animals in a total of 23 different stages, E(es-s) showed a good correlation and agreement with invasively determined E(es) (y = 0.84 x + 0.38; r = 0.8; P < .01, mean difference = 0.1 +/- 0.6 mm Hg/mL). In the clinical study, preoperative E(es-s) (r = 0.77; P < .001) and end-systolic volume index correlated well with postoperative ejection fraction (r = -0.69; P < .001). Multivariate analyses revealed that only E(es-s) was an independent predictor of postoperative LV function. Preoperative E(es-s) less than or equal to 1.0 mm Hg/mL was most predictive for identifying patients with LV dysfunction after surgery (sensitivity 87%; specificity 76%).

    CONCLUSIONS LV end-systolic elastance can be estimated noninvasively and is useful to detect latent LV dysfunction in patients with MR before surgery.

    PubMed IF 8.3 순환기내과
25. 2442007

    제1저자 이근욱 · 교신저자 김지현

    Lee KW, Kim JH, Yun T, Song EK, Na II, Shin H, Oh SY, Choi IS, Oh DY, Kim DW, Im SA, Kim TY, Lee JS, Heo DS, Bang YJ, Kim NK

    Phase II study of low-dose paclitaxel and cisplatin as a second-line therapy after 5-fluorouracil/platinum chemotherapy in gastric cancer.

    J Korean Med Sci. 2007;22 Suppl(Suppl):S115-21.

    Abstract

    This study was performed to evaluate the efficacy and toxicity of low-dose paclitaxel/cisplatin chemotherapy in patients with metastatic or recurrent gastric cancer that had failed 5-fluorouracil/platinum-based chemotherapy. Thirty-two patients with documented progression on or within 6 months after discontinuing 5-fluorouracil/platinum-based chemotherapy were enrolled. As a second-line treatment, paclitaxel (145 mg/m(2)) and cisplatin (60 mg/m(2)) was administered on day 1 every 3 weeks. Among 32 patients enrolled, 8 (25%) responded partially to paclitaxel/cisplatin, 8 (25%) had stable disease, and 14 (44%) had progressive disease. Two patients (6%) were not evaluable. The median time to progression (TTP) and overall survival for all patients were 2.9 months and 9.1 months, respectively. The most common hematologic toxicity was anemia (47%). Grade 3 neutropenia developed in three patients (9%), but no other grade 3/4 hematologic toxicity occurred. The most common non-hematologic toxicities were emesis (31%) and peripheral neuropathy (38%). Three cases (9%) of grade 3/4 emesis and 2 cases (6%) of grade 3 peripheral neuropathy developed. In conclusion, low-dose paclitaxel and cisplatin chemotherapy showed moderate activity with favorable toxicity profiles. However, relatively short TTP of this regimen warrants the development of more effective paclitaxel-based regimens other than combination with cisplatin in these patients as second-line therapies.

    PubMed IF 3.2 혈액종양내과
26. 2432007

    제1저자 최의근 · 교신저자 김효수,구본권

    Choi EK, Koo BK, Kim HS, Cho YM, Kang HJ, Cho YS, Chung WY, Chae IH, Choi DJ, Oh BH, Park YB, Choi YS

    Prognostic significance of asymptomatic coronary artery disease in patients with diabetes and need for early revascularization therapy.

    Diabet Med. 2007;24(9):1003-11.

    Abstract

    AIMS Information on the clinical outcome of patients with diabetes with silent myocardial ischaemia is limited. We compared the clinical and angiographic characteristics, and the clinical outcomes of diabetic patients with asymptomatic or symptomatic coronary artery disease (CAD).

    METHODS Three hundred and ten consecutive diabetic patients with CAD were divided into two groups according to the presence of angina and followed for a mean of 5 years. Fifty-six asymptomatic patients with a positive stress test and CAD on coronary angiography were compared with 254 symptomatic patients, 167 with unstable angina and 87 with chronic stable angina.

    RESULTS Although the severity of coronary atherosclerosis was similar in asymptomatic and symptomatic patients, revascularization therapy was performed less frequently in the asymptomatic than the symptomatic patients (26.8 vs. 62.0%; P < 0.001). Asymptomatic patients experienced a similar number of major adverse cardiac events (MACEs; death, non-fatal myocardial infarction, and revascularization; 32 vs. 28%; P = 0.57), but had higher cardiac mortality than symptomatic patients (26 vs. 9%; P < 0.001). However, patients who underwent revascularization therapy at the time of CAD diagnosis in these two groups showed similar MACE and cardiac mortality (20.0 vs. 22.5%, 6.7 vs. 5.3%, respectively; all P > 0.05).

    CONCLUSIONS This study suggests that diabetic patients with asymptomatic CAD have a higher cardiac mortality risk than those with symptomatic CAD, and that lack of revascularization therapy may be responsible for the poorer survival.

    PubMed IF 3.3 순환기내과
27. 2422007

    제1저자 김상현 · 교신저자 김효수

    Kim SH, Kim YD, Lim DS, Yoon MH, Ahn YK, On YK, Lee JW, Kim IJ, Park JB, Kim JJ, Chung WS, Yang JY, Seo HS, Shin EK, Kim HS, Korean Multicenter Amlodipine Study Investigators

    Results of a phase III, 8-week, multicenter, prospective, randomized, double-blind, parallel-group clinical trial to assess the effects of amlodipine camsylate versus amlodipine besylate in Korean adults with mild to moderate hypertension.

    Clin Ther. 2007;29(9):1924-36.

    Abstract

    BACKGROUND Amlodipine besylate has been used in Korea for the treatment of hypertension for >17 years, with well-established efficacy and tolerability. Amlodipine camsylate is a newer formulation developed for generic use. It has been assessed in terms of physical stability and pharmacokinetic and pharmacodynamic properties and been found to be effective in lowering blood pressure in preclinical and Phase I and II trials. However, to date, no studies have compared the clinical effectiveness of amlodipine camsylate and amlodipine besylate in treating hypertension.

    OBJECTIVE This study was designed to determine the effectiveness and tolerability of amlodipine camsylate compared with amlodipine besylate in Korean patients with mild to moderate hypertension.

    METHODS This Phase III, 8-week, prospective, randomized, double-blind, parallel-group study was conducted in 13 cardiology centers across the Republic of Korea. Male and female Korean patients aged 18 to 75 years having uncomplicated, mild to moderate, essential hypertension (sitting diastolic blood pressure [SiDBP] 90-<110 mm Hg) and receiving no antihypertensives in the 2 weeks before randomization were eligible. Patients were randomly assigned to receive oral treatment with amlodipine camsylate or amlodipine besylate. For the first 4 weeks, patients received amlodipine 5 mg QD (morning). After 4 weeks, if either blood pressure was > or =140/ > or =90 mm Hg or SiDBP had not decreased by > or =10 mm Hg from baseline, the dose of amlodipine was increased to 10 mg QD for 4 weeks. Trough blood pressure and heart rate were measured in duplicate with the patient in the sitting position at each clinic visit (baseline [week 0] and weeks 4 and 8 of treatment); mean values were calculated and recorded. At weeks 4 and 8, tolerability was assessed using history taking and laboratory analysis, and compliance was assessed using pill counts. The primary end point was change from baseline in SiDBP at week 8. Secondary end points were change from baseline in sitting systolic blood pressure (SiSBP) at week 8 in the total population and in the subgroup of patients who had previously received antihypertensive treatment versus those who had not.

    RESULTS A total of 189 patients were enrolled (mean age, 53 years; 105 women, 84 men; mean body weight, 65.8 kg). One patient in the amlodipine camsylate group dropped out of the study at week 0 of treatment (this patient did not use any study medication) and was excluded from the modified intent-to-treat (ITT) analysis. Thus, 188 patients were treated and included in the ITT analysis (94 patients per treatment group; ITT analysis); 161 patients were included in the perprotocol (PP) analysis (n = 80 for amlodipine camsylate, n = 81 for amlodipine besylate) (14 patients in the amlodipine camsylate group and 13 patients in the amlodipine besylate group were excluded from the PP analysis due to consistent withdrawal or protocol violation). Mean (SD) SiSBP and SiDBP were significantly decreased from baseline in both groups (amlodipine camsylate, from 146.7 [12.3]/96.6 [5.4] to 127.9 [14.8]/83.4 [7.7] mm Hg [both, P < 0.001]; amlodipine besylate, from 146.8 [12.8]/96.7 [5.1] to 128.0 [10.1]/83.8 [7.5] mm Hg [both, P < 0.001]). The differences in SiSBP/SiDBP between the 2 groups at week 8 were not significant. The SiDBP response rates in the subgroups that had and had not been previously treated with antihypertensives were statistically similar (56/69 [81.2%] and 83/92 [90.2%], respectively). The prevalences of clinical adverse events (AEs) were not significantly different between the 2 treatment groups (amlodipine camsylate, 27.3 %; amlodipine besylate, 28.7%). The most common AEs were dizziness and dyspnea (both in 3/94 [3.2%] and 1/94 [1.1%] patients who received amlodipine camsylate and amlodipine besylate, respectively).

    CONCLUSION The effectiveness and tolerability of amlodipine camsylate were not significantly different from those of amlodipine besylate in these Korean adults with mild to moderate hypertension.

    PubMed IF 3.7
28. 2412007

    제1저자 유지연 · 교신저자 김나영

    Yoo JY, Kim N, Park YS, Hwang JH, Kim JW, Jeong SH, Lee HS, Choe C, Lee DH, Jung HC, Song IS

    Detection rate of Helicobacter pylori against a background of atrophic gastritis and/or intestinal metaplasia.

    J Clin Gastroenterol. 2007;41(8):751-5.

    Abstract

    BACKGROUND To evaluate the detection rate of the CLOtest, Giemsa stain, and culture for the diagnosis of Helicobacter pylori organisms in patients with or without atrophic gastritis (AG) and/or intestinal metaplasia (IM).

    METHODS We used either the CLOtest, Giemsa staining, or culture to determine the presence of H. pylori in 430 participants who were documented to be infected with H. pylori from September 2003 to June 2006. The detection rates of the methods were evaluated according to the presence of AG and IM in antrum and body, which were classified using the updated Sydney system classification.

    RESULTS Positivity by the CLOtest markedly reduced depending on the degree of AG and IM in both antrum and body (P<0.05), and the positivity of Giemsa staining was markedly reduced as the degree of IM increased (P<0.01), but was not affected by the degree of AG (P=0.08) in antrum or body. When the results of these tests were evaluated in terms of combinations of AG and IM, the positivity of CLOtest was found to be lower in AG with IM than in AG without IM, (50.0% vs. 80.0% in antrum, 47.5% vs. 78.0% in body, respectively, P<0.01). In addition, the positivity of Giemsa stain was less frequent in AG with IM than in AG without IM in antrum (65.1% vs. 100%, respectively, P<0.01). However, the positivity of Giemsa stain in the body showed no statistical difference between AG without IM and AG with IM (97.6% vs. 91.7%, respectively).

    CONCLUSIONS Invasive H. pylori tests, especially the CLOtest, had a lower detection rate for H. pylori in the presence of mucosal atrophy and IM, and this became more prominent in the presence of higher levels of IM and AG.

    PubMed IF 2.7 소화기내과
29. 2402007

    제1저자 김 원 · 교신저자 윤정환

    Kim W, Yoon JH, Jeong JM, Cheon GJ, Lee TS, Yang JI, Park SC, Lee HS

    Apoptosis-inducing antitumor efficacy of hexokinase II inhibitor in hepatocellular carcinoma.

    Mol Cancer Ther. 2007;6(9):2554-62.

    Abstract

    Hypoxia stimulates hepatocellular carcinoma (HCC) cell growth via hexokinase (HK) II induction, and alternatively, HK II inhibition induces apoptosis by activating mitochondrial signaling. This study was to investigate whether the induction of HK II by hypoxia is associated with enhanced mitochondrial stability and to confirm the apoptosis-inducing efficacy of HK II inhibitor in an in vivo model of HCC. Mitochondrial stability was examined by treating isolated mitochondria with deoxycholate, a permeability-enhancing agent. Alteration of permeability transition pore complex composition was analyzed by immunoprecipitation and immunoblotting. An in vivo model of HCC was established in C3H mice i.d. implanted with MH134 cells. The antitumor efficacy of i.p. given 3-bromopyruvate (3-BrPA), a HK II inhibitor, was evaluated by measuring tumor volumes and quantifying apoptosis using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining and (99m)Tc-hydrazinonicotinamide-Annexin V scans. Hypoxia enhanced mitochondrial stability, and this was inhibited by 3-BrPA treatment. In particular, HK II levels in permeability transition pore complex immunoprecipitates were reduced after 3-BrPA treatment. In mice treated with 3-BrPA, mean tumor volumes and tumor volume growth were found to be significantly reduced. Moreover, percentages of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were significantly increased in 3-BrPA-treated mice, and this apoptosis-inducing efficacy was reflected in vivo by (99m)Tc-hydrazinonicotinamide-Annexin V imaging. Our results show that hypoxia enhances mitochondrial stability via HK II induction and that HK II inhibitor treatment exhibits an in vivo antitumor effect by inducing apoptosis. Therefore, HK II inhibitors may be therapeutically useful for the treatment of advanced infiltrative hypovascular HCCs, which are growing in a hypoxic environment.

    PubMed IF 6.9 소화기내과
30. 2392007

    제1저자 이윤종 · 교신저자 송영욱

    Lee YJ, Kang SW, Song JK, Baek HJ, Choi HJ, Bae YD, Ryu HJ, Lee EY, Lee EB, Song YW

    Associations between interferon regulatory factor-1 polymorphisms and Behçet's disease.

    Hum Immunol. 2007;68(9):770-8.

    Abstract

    Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates the functions of type I and II interferons and plays a role in host protection. Behçet's disease (BD) is an idiopathic systemic vasculitis that is often complicated with thrombotic features, and infectious agents have long been postulated to be a disease-triggering factor in its pathogenesis. The authors investigated the distributions of IRF-1 promoter -415 C/A, -410 A/G, and -300 A/G, and 3'-untranslated region (UTR) A/G polymorphisms in 105 BD patients (mean age 41.7 +/- SEM 1.1 years, 44 male and 61 female) and in 105 gender- and age-matched healthy controls. The frequencies of individual alleles and genotypes were not different between the control and BD groups. However, the frequency of AGGG haplotype was significantly higher (73.5% vs 60.2%, odds ratio [OR] = 1.842, 95% confidence interval [95% CI] = 1.219-2.783, p(c) = 0.036) and that of the CAAG haplotype was significantly lower (2.2% vs 9.5%, OR = 0.195, 95% CI = 0.068-0.559, p(c) = 0.02) in BD patients than in healthy controls. In addition, the frequency of the AGGG haplotype was significantly higher (80.3% vs 57.4%, OR = 3.033, 95% CI = 1.716-5.360, p(c) = 0.001) and that of the CAAG haplotype was significantly lower (0.8% vs 12.3%; OR = 0.059, 95% CI = 0.010-0.357, p(c) = 0.005) in female BD patients than female controls. By subgroup analyses, the CAAA haplotype tended to be more common in BD patients with moderate or severe disease than in those with mild disease (25.4% vs 13.6%, OR = 2.158, 95% CI = 1.046-4.440, p = 0.037 before Bonferroni correction). When BD patients were subclassified by a history of deep vein thrombosis (DVT), the CAAA haplotype was found to be significantly increased the risk of DVT (42.1% vs 15.7%, OR = 3.906, 95% CI = 1.836-8.324, p(c) = 0.0015) and the AGGG haplotype tended to reduce this risk (57.9% vs 77.3%, OR = 0.403, 95% CI = 0.195-0.834, p(c) = 0.0685). Furthermore, the frequency of the CAAA haplotype was significantly higher in BD patients that had experienced a thrombotic event than in those that had not (40.5% vs 15.5%, OR = 3.7147, 95% CI = 1.778-7.770, p(c) = 0.0015). These results suggest that IRF-1 is a novel susceptibility gene in BD, especially in women, and furthermore, that IRF-1 polymorphisms may be related to thrombosis in BD patients.

    PubMed IF 2.1 류마티스내과

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.