SCI 발표논문

1. 1292007

   제1저자 최창민 · 교신저자 임재준

   Choi C-M, Hwang SS, Lee C-H, Lee HW, Kang C-I, Kim C-H, Han SK, Shim Y-S, and Yim J-J

   Latent TB infection diagnosed by a whole blood interferon g assay in military settings

   Respirology. 2007;12:898-901.

   IF 1.46 호흡기내과
2. 1282007

   제1저자 이승표 · 교신저자 김효수

   Lee S-P, Yoon S-W, Kim H-S

   Integrin-linked Kinase: It's Role in the Vascular System

   Internal J of Biomedical Science. 2007;3(1):1-8.

   IF 1.38 순환기내과
3. 1272007

   제1저자 윤영호 · 교신저자 허대석

   Yun YH, Kwak M, Park SM, Kim S, Choi JS, Lim HY, Lee CG, Choi YS, Hong YS, Kim SY, Heo DS

   Chemotherapy use and associated factors among cancer patients near the end of life.

   Oncology. 2007;72(3-4):164-71.

   Abstract

   OBJECTIVES We investigated the frequency of chemotherapy use and its associated factors in patients in all age groups in the last year of life.

   METHODS We identified cancer patients who died in 2004 in any of 17 hospitals. We used demographic and treatment characteristics by computerized hospital information systems and by linking the identification numbers to the 2004 death registry.

   RESULTS 48.7% of patients in the last 6 months of life, 43.9% in the last 3 months, and 30.9% in the last month of life received chemotherapy. The frequency of chemotherapy use was lower for older patients. In those > or =65 years old, there was no difference between women and men in the proportion that received chemotherapy. For patients <65 years of age, a larger proportion of women than men received chemotherapy, and chemotherapy use was significantly less frequent for patients with refractory disease than for those with responsive disease. Patients dying at a relatively small hospital without a hospice inpatient unit were significantly more likely to receive chemotherapy.

   CONCLUSIONS Despite the fact that most cancer patients are resistant to chemotherapy at the end of life, it was administered often to all age groups.

   PubMed IF 1.9 혈액종양내과
4. 1262007

   제1저자 김광일 · 교신저자 김철호

   Kim KI, Na JE, Kang SY, Cho YS, Choi DJ, Kim CH, Kim HS, Oh BH, Choi YH, Kwon IS, Park SC

   Impact of NAD(P)H oxidase p22 phox gene polymorphism on vascular aging in Korean centenarian and nonagenarian.

   Int J Cardiol. 2007;123(1):18-22.

   Abstract

   BACKGROUND Oxidative stress, the imbalance between production and removal of reactive oxygen species (ROS), is implicated in the process of cardiovascular aging. Membrane-associated NAD(P)H oxidase system is the most important source of ROS in vascular cells. p22(phox), a critical component of the NAD(P)H oxidase, has a polymorphic site on exon 4, associated with variable enzyme activity. The goal of this study is to investigate the effect of the p22(phox) C242T polymorphism on cardiovascular aging.

   METHODS We investigated, in a cross-sectional study, the distribution of the p22(phox) genotypes and its impact on vascular aging in elderly Korean subjects (N=123, mean age+/-SD: 97.0+/-5.0). p22(phox) C242T polymorphism was determined by PCR and restriction fragment length polymorphism analysis. The p22(phox) genotype and allele frequencies were also compared with younger Korean subjects (N=363, mean age+/-SD: 49.0+/-10.3).

   RESULTS No significant difference was identified in p22(phox) genotype frequency according to the subject's age. However, the prevalence of CT+TT genotype was significantly less frequent in normotensive extremely elderly compared with younger subjects. Furthermore, the prevalence of the CT+TT genotype was significantly more frequent in hypertensive subjects (21.9%) than in the normotensive group (6.0%, P=0.016) in extremely elderly subject. The association was more significant in systolic hypertension rather than diastolic hypertension. Mean systolic blood pressure and pulse pressure were also significantly higher in subjects with CT+TT genotype. In contrast, there was no significant association between p22(phox) genotype and hypertension in younger-aged group.

   CONCLUSION These results suggest an association between the p22(phox) C242T polymorphism and vascular aging, which might be mediated by the increase of oxidative stress.

   PubMed IF 3.3 노인병내과
5. 1252007

   제1저자 오일영 · 교신저자 김효수,박영배

   Oh IY, Yoon CH, Hur J, Kim JH, Kim TY, Lee CS, Park KW, Chae IH, Oh BH, Park YB, Kim HS

   Involvement of E-selectin in recruitment of endothelial progenitor cells and angiogenesis in ischemic muscle.

   Blood. 2007;110(12):3891-9.

   Abstract

   E-selectin plays critical roles in tethering leukocytes to endothelial cells (ECs). We studied the role of E-selectin in endothelial progenitor cell (EPC) homing and vasculogenesis. After ischemia, the expression of E-selectin on ECs peaked 6 to 12 hours and returned to baseline at 24 hours, whereas the level of soluble E-selectin (sE-selectin) in serum increased over 24 hours and remained high at day 7. Mouse bone marrow-derived EPCs expressed not only E-selectin but also its ligand. Homing of circulating EPCs to ischemic limb was significantly impaired in E-selectin knock-out mice, as well as wild-type mice pretreated with blocking antibody against E-selectin, which was rescued by local sE-selectin injection. Mechanism for this is that sE-selectin stimulated not only ECs to express ICAM-1, but also EPCs to secrete interleukin-8 (IL-8), leading to enhanced migration and incorporation to ECs capillary formation. In therapeutic aspect, local treatment with sE-selectin enhanced efficacy of EPC transplantation for vasculogenesis and salvage of ischemic limb. Conversely, when E-selectin was knocked down by E-selectin small interfering RNA, blood flow recovery after EPC transplantation was significantly impaired. But this impaired vasculogenesis was rescued by sE-selectin. In conclusion, these data demonstrate E-selectin is a pivotal molecule for EPCs' homing to ischemic limb and vasculogenesis.

   PubMed IF 23.9 순환기내과
6. 1242007

   제1저자 강정묵 · 교신저자 김나영

   Kang JM, Kim N, Lee DH, Park YS, Kim YR, Kim JS, Jung HC, Song IS

   Second-line treatment for Helicobacter pylori infection: 10-day moxifloxacin-based triple therapy versus 2-week quadruple therapy.

   Helicobacter. 2007;12(6):623-8.

   Abstract

   BACKGROUND AND AIM The aim of this study was to test the efficacy of 10-day moxifloxacin-based triple therapy versus 2-week quadruple therapy for the second-line treatment of Helicobacter pylori infection.

   METHODS One hundred and ninety-two patients who had failed previous H. pylori eradication on standard triple therapy were randomized to one of two regimens: 1, moxifloxacin (400 mg q.d.), amoxicillin (1000 mg b.i.d.), and esomeprazole (20 mg b.i.d.) for 10 days (the 10MEA group), or 2, esomeprazole (20 mg b.i.d.), tripotassium dicitrate bismuthate (300 mg q.i.d.), metronidazole (500 mg t.i.d.), and tetracycline 500 mg (q.i.d.) for 14 days (the 14EBMT group). The eradication rates, drug compliances, and side-effect rates of these two regimens were compared.

   RESULTS Eradication rates by intention-to-treat and per-protocol analyses in the 10MEA and 14EMBT groups were 71.9% and 82.6%, and 71.7% and 90.5% (p = .973 and .321), respectively. The 10MEA group was significantly superior to the 14EMBT group in terms of side-effect rates (12.2% vs. 39.6%, p = .001), and discontinuation rates due to side-effects were lower in the 10MEA group than in the 14EMBT group (0.7% vs. 13.2%, p < .001). Moreover, compliance was higher in the 10MEA group (94.2% (131/139)) than in the 14EBMT group (83.0% (44/53)) (p = .014).

   CONCLUSION The 10-day moxifloxacin-based triple therapy was found to have a high eradication rate with few side-effects and good drug compliance. These findings suggest that this regimen is a safe and effective second-line treatment option for H. pylori infection in Korea.

   PubMed IF 4.6 소화기내과
7. 1232007

   제1저자 김경원 · 교신저자 조보연

   Kim KW, Park YJ, Kim TY, Park DJ, Park KS, Cho BY

   Susceptible alleles of the CD40 and CTLA-4 genes are not associated with the relapse after antithyroid withdrawal in Graves' disease.

   Thyroid. 2007;17(12):1229-34.

   Abstract

   In this study, we investigated whether the CD40 or cytotoxic T lymphocyte-associated molecules-4 (CTLA-4) polymorphisms, which are associated with the susceptibility of Graves' disease (GD), can predict the clinical outcome after antithyroid drug (ATD) withdrawal. All patients with GD were treated with ATD. GD patients were divided into two groups: remission or failure. The remission group was defined as patients who maintained a euthyroid state for 1 year after ATD withdrawal. The failure group was defined as patients who relapsed within 1 year after the discontinuation of ATD or who could not discontinue their ATD treatment within 24 months. The rate of treatment failure after ATD withdrawal was 72.2%. For the susceptible genes, the CC genotype in the CD40, the GG genotype in the CTLA-4 exon 1, and the CC genotype in the CTLA-4 promoter region have shown no significant association with a clinical outcome after ATD withdrawal. However, clinical parameters, such as male gender, severe thyrotoxicosis, high thyroid-stimulating hormone-binding inhibitory immunoglobulin value, and a large goiter, were related to treatment failure. These findings suggest that the genetic markers associated with the development of GD cannot be used to predict the relapse of GD patients in place of clinical parameters.

   PubMed IF 6.6 내분비대사내과
8. 1222007

   제1저자 김동완 · 교신저자 허대석

   Kim DW, Kim SY, Kim HK, Kim SW, Shin SW, Kim JS, Park K, Lee MY, Heo DS

   Multicenter phase II trial of Genexol-PM, a novel Cremophor-free, polymeric micelle formulation of paclitaxel, with cisplatin in patients with advanced non-small-cell lung cancer.

   Ann Oncol. 2007;18(12):2009-14.

   Abstract

   BACKGROUND Genexol-PM is a novel Cremophor EL (CrEL)-free polymeric micelle formulation of paclitaxel (Taxol). This multicenter phase II study was designed to evaluate the efficacy and safety of the combination of Genexol-PM and cisplatin for the treatment of advanced non-small-cell lung cancer (NSCLC).

   PATIENTS AND METHODS Patients with advanced NSCLC received Genexol-PM 230 mg/m(2) and cisplatin 60 mg/m(2) on day 1 of a 3-week cycle as first-line therapy. Intrapatient dose escalation of Genexol-PM to 300 mg/m(2) was carried out from the second cycle if the prespecified toxic effects were not observed after the first cycle.

   RESULTS Sixty-nine patients were enrolled in this study. Overall response rate was 37.7%. The median time to progression was 5.8 months and the median survival period was 21.7 months. The major non-hematologic toxic effects included grade 3 peripheral sensory neuropathy (13.0%) and grade 3/4 arthralgia (7.3%). Four patients (5.8%) experienced grade 3/4 hypersensitivity reactions. The major hematological toxic effects were grade 3/4 neutropenia (29.0% and 17.4%, respectively).

   CONCLUSION Genexol-PM plus cisplatin combination chemotherapy showed significant antitumor activity. The use of CrEL-free, polymeric micelle formulation of paclitaxel allowed administration of higher doses of paclitaxel compared with the CrEL-based formulation without significant increased toxicity.

   PubMed IF 80.4 혈액종양내과
9. 1212007

   제1저자 이석묵 · 교신저자 안규리

   Lee S, Chung J, Ha IS, Yi K, Lee JE, Kang HG, Choi I, Oh KH, Kim JY, Surh CD, Ahn C

   Hydrogen peroxide increases human leukocyte adhesion to porcine aortic endothelial cells via NFkappaB-dependent up-regulation of VCAM-1.

   Int Immunol. 2007;19(12):1349-59.

   Abstract

   Although a severe shortage of organs in transplantation can be overcome by using xenotransplantation of porcine donor organs, profound immune rejection to xenogeneic antigens remains a main obstacle. To elucidate the role of hydrogen peroxide (H(2)O(2)) on xenogeneic immune responses, we investigated its effects on porcine aortic endothelial cells (PAECs). We found that H(2)O(2) can specifically induce vascular cell adhesion molecule-1 (VCAM-1) expression on PAECs, but little on human umbilical vein endothelial cells (HUVECs) and aortic endothelial cells (HAECs). Furthermore, we further confirmed that H(2)O(2) induces activation of NFkappaB in PAECs, but not in HAECs. Interestingly, cell adhesion assay showed that U937, human promonocytic leukocyte, can adhere to PAECs in an H(2)O(2)-dependent manner and by using a neutralizing assay with anti-VCAM-1-specific antibodies, we also found that the interaction is mediated primarily by VCAM-1. Finally, we also demonstrated that up-regulation of VCAM-1 expression on PAECs by reactive oxygen species-producing HL-60, human leukemic neutrophil cells, could be significantly diminished by over-expressing an H(2)O(2)-removing catalase. In summary, our results suggest that NFkappaB-dependent porcine VCAM-1 expression by H(2)O(2) may promote interaction of human leukocyte to PAECs, and thus may play an important role on inducing xenogeneic immune responses.

   PubMed IF 3.4 신장내과
10. 1202007

    제1저자 오윤규 · 교신저자 나기영

    Oh YK, Joo KW, Lee JW, Jeon US, Lim CS, Han JS, Knepper MA, Na KY

    Altered renal sodium transporter expression in an animal model of type 2 diabetes mellitus.

    J Korean Med Sci. 2007;22(6):1034-41.

    Abstract

    Hemodynamic factors play an important role in the development and/or progression of diabetic nephropathy. We hypothesized that renal sodium transporter dysregulation might contribute to the hemodynamic alterations in diabetic nephropathy. Otsuka Long Evans Tokushima Fatty (OLETF) rats were used as an animal model for type 2 diabetes. Long Evans Tokushima (LETO) rats were used as controls. Renal sodium transporter regulation was investigated by semiquantitative immunoblotting and immunohistochemistry of the kidneys of 40-week-old animals. The mean serum glucose level in OLETF rats was increased to 235+/-25 mg/dL at 25 weeks, and the hyperglycemia continued up to the end of 40 weeks. Urine protein/ creatinine ratios were 10 times higher in OLETF rats than in LETO rats. At 40th week, the abundance of the epithelial sodium channel (ENaC) beta-subunit was increased in OLETF rats, but the abundance of the ENaC gamma-subunit was decreased. No significant differences were observed in the ENaC alpha-subunit or other major sodium transporters. Immunohistochemistry for the ENaC beta-subunit showed increased immunoreactivity in OLETF rats, whereas the ENaC gamma-subunit showed reduced immunoreactivity in these rats. In OLETF rats, ENaC beta-subunit upregulation and ENaC gamma-subunit downregulation after the development of diabetic nephropathy may reflect an abnormal sodium balance.

    PubMed IF 3.2 신장내과
11. 1192007

    제1저자 김형관 · 교신저자 김용진

    Kim HK, Kim YJ, Chang SA, Kim SY, Jang HJ, Lee W, Park JS, Sohn DW, Oh BH, Park YB, Choi YS

    Clinical validity of longitudinal pre-ejectional myocardial velocity for identifying the transmural extent of viable myocardium: early after reperfusion of an infarct-related coronary artery.

    Circ J. 2007;71(12):1904-11.

    Abstract

    BACKGROUND Positive longitudinal pre-ejectional velocity (+PEVL) was recently reported to be a reliable index of myocardial recovery early after successful revascularization in myocardial infarction (MI); that is, it recognizes the transmural extent of viable myocardium. The applicability of PEVL in the real-world clinical setting for identifying the transmural extent of viable myocardium in reperfused recent MI was assessed.

    METHODS AND RESULTS Using tissue Doppler imaging, the resting basal and mid myocardial PEVLs were determined within 3 days after revascularization in 41 consecutive patients with recent MI. Infarct thickness was semi-quantified using delayed gadolinium-enhanced magnetic resonance imaging (MRI) at baseline and at 6-month follow up to differentiate transmural from nontransmural MI. The proportion of segments showing the presence of +PEVL was not significantly changed as infarct thickness increased (p=0.2), with 66.2% having +PEVL even in segments involving >75% transmural infarction. Moreover, +PEVL was found in a large fraction of segments with akinesia (70.4%). Specificity and negative predictive value of +PEVL for assessing infarct nontransmurality were disappointingly low (32.0% and 26.9%, respectively). All of these results were not altered when the 6-month follow-up MRI was done.

    CONCLUSIONS +PEVL cannot be regarded as a reliable marker for predicting the transmural extent of viable myocardium in recent MI.

    PubMed IF 5.8 순환기내과
12. 1182007

    제1저자 박병래 · 교신저자 이효석

    Park BL, Kim YJ, Cheong HS, Lee SO, Han CS, Yoon JH, Park JH, Chang HS, Park CS, Lee HS, Shin HD

    HDAC10 promoter polymorphism associated with development of HCC among chronic HBV patients.

    Biochem Biophys Res Commun. 2007;363(3):776-81.

    Abstract

    Histone deacetylases (HDACs) are key enzymes responsible for the removal of acetyl groups from acetylated histone and non-histone proteins, and play important roles in various biological processes including transcription regulation and DNA repair. In this study, we identified 22 sequence variants by direct DNA sequencing in 24 individuals and five common variant were selected for genotyping in larger-scale subjects (n=1095). Statistical analysis revealed that HDAC10-589C>T was significantly associated with HCC occurrence among chronic HBV patients (OR=2.39, P(cor)=0.04) as well as HCC acceleration among chronic HBV patients (RH=1.97, Pcor=0.002). Functional assay also revealed that luciferase activity of "T" allele was significantly higher than that of "C" allele of HDAC10-589C>T (P=0.023). These results suggest that the "T" allele of HDAC10-589C>T affect on the increased transcription activity, and might accelerate HCC development through increased expression of HDAC10.

    PubMed IF 2.5 소화기내과
13. 1172007

    제1저자 김혜련 · 교신저자 임재준

    Kim HR, Hwang SS, Kim HJ, Lee SM, Yoo CG, Kim YW, Han SK, Shim YS, Yim JJ

    Impact of extensive drug resistance on treatment outcomes in non-HIV-infected patients with multidrug-resistant tuberculosis.

    Clin Infect Dis. 2007;45(10):1290-5.

    Abstract

    BACKGROUND Recently, serious concerns about extensively drug-resistant tuberculosis (XDR-TB), which shows resistance to second-line anti-TB drugs in addition to isoniazid and rifampicin, have been raised. The aim of this study was to elucidate the impact of extensive drug resistance on treatment outcomes in non-human immunodeficiency virus (HIV)-infected patients with multidrug-resistant tuberculosis (MDR-TB).

    METHODS Patients who received the diagnosis of and treatment as having MDR-TB at Seoul National University Hospital (Seoul, Republic of Korea) between January 1996 and December 2005 were included. The definition of XDR-TB was TB caused by bacilli showing resistance to both isoniazid and rifampicin and also showing resistance to any fluoroquinolone and to at least 1 of the following 3 injectable anti-TB drugs: capreomycin, kanamycin, and amikacin. To identify the impact of extensive drug resistance on treatment outcomes, univariate comparison and multiple logistic regression were performed.

    RESULTS A total of 211 non-HIV-infected patients with MDR-TB were included in the final analysis. Among them, 43 patients (20.4%) had XDR-TB. Treatment failure was observed in 19 patients (44.2%) with XDR-TB, whereas treatment of 46 patients (27.4%) with non-XDR-TB failed (P=.057). The presence of extensive drug resistance (adjusted odds ratio [OR], 4.46; 95% confidence interval [CI], 1.35-14.74) and underlying comorbidity (adjusted OR, 2.62; 95% CI, 1.00-6.87) were independent risk factors for treatment failure. However, a higher level of albumin was inversely associated with treatment failure (adjusted OR, 0.87; 95% CI, 0.77-0.97).

    CONCLUSION The presence of extensive drug resistance, the presence of comorbidity, and hypoalbuminemia were independent poor prognostic factors in non-HIV-infected patients with MDR-TB.

    PubMed IF 8.3 호흡기내과
14. 1162007

    제1저자 김성한 · 교신저자 오명돈

    Kim SH, Choi SJ, Kim HB, Kim NJ, Oh MD, Choe KW

    Diagnostic usefulness of a T-cell based assay for extrapulmonary tuberculosis.

    Arch Intern Med. 2007;167(20):2255-9.

    Abstract

    BACKGROUND Diagnosing extrapulmonary tuberculosis (E-TB) remains a challenge. A recently developed Mycobacterium tuberculosis-specific region of difference 1 gene-based assay for diagnosing tuberculosis infection showed promising results. However, the diagnostic usefulness of this assay remains to be determined compared with tuberculin skin test (TST) in patients with suspected E-TB in clinical practice.

    METHODS All patients with suspected E-TB were prospectively enrolled in a tertiary care hospital during a 9-month period. In addition to the conventional tests for diagnosing E-TB, the interferon gamma-producing T-cell responses to early secreted antigenic target 6 and culture filtrate protein 10 by enzyme-linked immunospot (ELISPOT) assay were performed. Final diagnosis in patients having suspected E-TB was classified by clinical category.

    RESULTS Seventy-two patients with suspected E-TB were enrolled; 34 (47%) had immunosuppressive conditions. Of 72 patients, 32 (44%) were classified as having E-TB, including 22 with confirmed tuberculosis and 10 with probable tuberculosis, and 35 (49%) were classified as not having tuberculosis. The remaining 5 (7%) had possible tuberculosis and were excluded from the final analysis. Chronic caseating granulomas, acid-fast bacilli stain, M tuberculosis polymerase chain reaction, and cultures for M tuberculosis were positive in 22 (69%), 5 (16%), 15 (47%), and 18 (56%), respectively, of 32 patients with E-TB. The sensitivity and specificity of the TST (induration size, > or =10 mm) were 47% (95% confidence interval [CI], 29%-65%) and 86% (95% CI, 70%-95%), respectively. By comparison, the sensitivity and specificity of the ELISPOT assay were 94% (95% CI, 79%-99%; P < .001 between TST and ELISPOT) and 88% (95% CI, 72%-97%; P =.99 between TST and ELISPOT), respectively.

    CONCLUSION The ELISPOT assay is a useful adjunct test for diagnosing E-TB.

    PubMed IF 7.92 감염내과
15. 1152007

    제1저자 이계숙 · 교신저자 안규리

    Yi KS, Lee S, Kang YH, Bae YS, Hwang SY, Ha I, Kim H, Kim MS, Cho B, Kang HJ, Bang KT, Kim JY, Yang J, Chung J, Ahn C

    Weak response of porcine C5a receptor towards human C5a in miniature pig endothelial cells and PMNs.

    Xenotransplantation. 2007;14(6):563-71.

    Abstract

    BACKGROUND The anaphylatoxin C5a is a potent inflammatory molecule generated during complement activation. Although some reports have implicated C5a in xenograft rejection, to date, the molecular compatibility between human C5a and porcine C5a receptor (C5aR) has been little studied. To examine the need for pC5aR-deficient pig in xenotransplantaion, we aimed to look at the degree of direct interaction between human C5a (recipient side) and porcine endothelial cells (PECs) and porcine polymorphonuclear neutrophils (PMNs) (donor side).

    METHODS Following the treatment of human C5a to isolated porcine PMNs, transmigration of PMNs was measured by Transwell system and superoxide generation by cytochrome c reduction assay. Next, the effects of human C5a on several intracellular signaling pathways were further checked; actin cytoskeletal change was observed under a confocal microscope after staining with Alexa Fluor-546-phalloidin, intracellular calcium mobilization was measured by spectrofluorophotometer. The degree of direct effect of human C5a on porcine PMNs was compared with that in human PMNs. Finally, microarray was performed to monitor the effect of human C5a on gene expression of PEC and the expression of several candidate proteins was checked by flow cytometry.

    RESULTS We found that human C5a was able to induce chemotaxis, superoxide generation, actin cytoskeletal change, and intracellular calcium mobilization in porcine PMNs. However, higher concentration of human C5a was required to stimulate porcine PMNs in comparison with activating human PMNs. The amino acid sequences of porcine C5aR with those of human C5aR showed a sequence homology of only 67%. To elucidate the effect of human C5a to PECs, microarray analysis following the treatment of PECs with human C5a was performed. These data showed that human C5a did not significantly affect gene transcription patterns in PECs. Additionally, treatment of PECs with human C5a also did not induce protein expression of several cell adhesion molecules, including vascular cell adhesion molecule-1, intercellular adhesion molecule-1, P-selectin, and E-selectin, or secretion of interleukin-8 from PECs.

    CONCLUSIONS These results suggest that human C5a may play a minor role on PEC activation possibly due to molecular incompatibility across the species barrier.

    PubMed IF 3.8 신장내과
16. 1142007

    제1저자 우상명 · 교신저자 류지곤

    Woo SM, Ryu JK, Lee SH, Yoo JW, Park JK, Kim YT, Jang JY, Kim SW, Kang GH, Yoon YB

    Recurrence and prognostic factors of ampullary carcinoma after radical resection: comparison with distal extrahepatic cholangiocarcinoma.

    Ann Surg Oncol. 2007;14(11):3195-201.

    Abstract

    BACKGROUND Ampullary carcinoma is often considered to have a better prognosis than distal extrahepatic cholangiocarcinoma. However, studies that directly compare the recurrence and histopathological features between the two groups are rare.

    METHODS Clinicopathologic factors and the long-term outcomes of 163 patients with ampullary carcinoma after radical resection were retrospectively evaluated and compared with those of 91 patients with distal extrahepatic cholangiocarcinoma.

    RESULTS Among the 163 ampullary carcinomas, T1 stage, well-differentiated tumors and perineural invasion were 45 (28%), 73 (45%), and 23 (14%), respectively, whereas, only five (6%) were T1 stage, 15 (17%) were well differentiated, and 63 (69%) showed perineural invasion (p < 0.001, for all) in distal extrahepatic cholangiocarcinomas. More patients with distal extrahepatic cholangiocarcinoma had liver metastasis than ampullary carcinoma (24% vs. 10%, p = 0.004). Multivariate analysis identified venous invasion and perineural invasion as risk factors for recurrence of ampullary carcinoma after radical resection. Only lymph node involvement was identified as a risk factor for recurrence of distal extrahepatic cholangiocarcinoma by multivariate analysis. Overall five-year survival of patients with ampullary cancer was higher than that of patients with distal extrahepatic cholangiocarcinoma (68% vs. 54%; p = 0.033). In patients without lymph node metastasis, a significant difference in survival was also observed between the two groups (p = 0.049).

    CONCLUSION Earlier diagnosis and the less frequent occurrence of pathological factors associated with tumor invasiveness in ampullary carcinoma than in distal extrahepatic cholangiocarcinoma may explain its association with a better prognosis.

    PubMed IF 3.8 소화기내과
17. 1132007

    제1저자 박흥우 · 교신저자 조상헌

    Park HW, Shin ES, Lee JE, Kim SH, Kim SS, Chang YS, Kim YK, Min KU, Kim YY, Cho SH

    Association between genetic variations in prostaglandin E2 receptor subtype EP3 gene (Ptger3) and asthma in the Korean population.

    Clin Exp Allergy. 2007;37(11):1609-15.

    Abstract

    BACKGROUND Recent investigations suggest that prostaglandin E2 (PGE2) is important in the pathogenesis of not only aspirin-intolerant asthma but also asthma unrelated to aspirin intolerance.

    OBJECTIVES This study was conducted to evaluate the effects of variations in the gene coding PGE2 receptor subtype EP1-4 (Ptger1-4) on the risk of asthma in the Korean population.

    METHODS Nineteen single nucleotide polymorphisms (SNPs) were selected after re-sequencing Ptger1-4 and were genotyped in 480 asthmatics and 140 healthy controls, who were randomly recruited.

    RESULTS By logistic regression analyses controlling for age and sex, 1388T>C in Ptger3 was found to be significantly associated with asthma [P=0.002, odds ratio (95% confidence interval)=0.63 (0.46-0.85) in the allele model], and this remained significant after applying the Bonferroni correction. In terms of haplotype, the frequency of the C-C-A-A haplotype in Ptger3 was significantly lower in asthmatics than in healthy controls (P=0.004). Moreover, the prevalence of this haplotype was significantly lower in moderate-to-severe asthmatics than in mild asthmatics (P=0.045; mild vs. moderate and P=0.034; mild vs. severe). However, no association was found between any genetic variation in Ptger1, Ptger2, or Ptger4 and asthma.

    CONCLUSION The present study demonstrated that genetic variations in Ptger3 are significantly associated with the risk and severity of asthma in the Korean population.

    PubMed IF 5 알레르기내과
18. 1122007

    제1저자 조영민,김진택 · 교신저자 박경수

    Cho YM, Kim JT, Ko KS, Koo BK, Yang SW, Park MH, Lee HK, Park KS

    Fulminant type 1 diabetes in Korea: high prevalence among patients with adult-onset type 1 diabetes.

    Diabetologia. 2007;50(11):2276-9.

    Abstract

    AIMS/HYPOTHESIS The aim of this study was to investigate the prevalence of fulminant type 1 diabetes and the clinical characteristics of the disease among newly diagnosed Korean patients.

    METHODS Using data retrieved from the Seoul National University Hospital database, we identified all patients newly diagnosed with type 1 diabetes from 1 January 1999 to 31 July 2006. Information on clinical manifestations and laboratory data, including the presence of islet autoantibodies detected at diagnosis, were obtained by reviewing medical records.

    RESULTS We identified 99 patients newly diagnosed with type 1 diabetes. Seven patients (7.1%) fulfilled the criteria for fulminant type 1 diabetes. Among the patients aged > or =18 years at onset, 30.4% had fulminant type 1 diabetes. Patients with this diabetes subtype tested negative for islet autoantibodies, had a higher age of onset (median 28 vs 10 years, p < 0.001) and a markedly shorter duration from onset of hyperglycaemic symptoms to first hospital visit (median 3 vs 30 days, p < 0.001) than patients with non-fulminant type 1 diabetes, and showed trends of increased serum aspartate aminotransferase and amylase levels and a decreased glucagon-stimulated serum C-peptide response.

    CONCLUSIONS/INTERPRETATION In Korea, the prevalence of fulminant type 1 diabetes was 7.1% among all patients newly diagnosed with type 1 diabetes and 30.4% among patients with adult-onset diabetes. The clinical and metabolic characteristics of the patients with fulminant type 1 diabetes were similar to those reported in Japanese studies.

    PubMed IF 10.4 내분비대사내과
19. 1112007

    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
20. 1102007

    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
21. 1092007

    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
22. 1082007

    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
23. 1072007

    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
24. 1062007

    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
25. 1052007

    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
26. 1042007

    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
27. 1032007

    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
28. 1022007

    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
29. 1012007

    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
30. 1002007

    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

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