SCI 발표논문

전체 4,588편

2982008

제1저자 예병덕 · 교신저자 김상균

, , , , , , , ,
Predictive factors for lymph node metastasis and endoscopic treatment strategies for undifferentiated early gastric cancer.
J Gastroenterol Hepatol. 2008;23(1):46-50.

Abstract
BACKGROUND AND AIM Although more than 80% of undifferentiated early gastric cancers (EGC) are not associated with lymph node metastasis, endoscopic mucosal resection is not generally accepted as a means of curative treatment because of an abundance of conflicting data concerning clinicopathological characteristics and prognoses. The aim of this study was to define a subgroup of undifferentiated EGC that could be cured by endoscopic treatment without the risk of lymph node metastasis.
METHOD A total of 591 patients surgically resected for undifferentiated EGC between January 1999 and March 2005 were reviewed. Associations between various clinicopathological factors and the presence of lymph node metastasis were analyzed to identify the risk factors of lymph node metastasis.
RESULTS Lymph node metastasis was found in 79 patients (13.4%). By multivariate logistic regression analysis, a tumor diameter 2.5 cm or larger, invasion into the middle third of the submucosal layer or deeper, and lymphatic involvement were identified as independent risk factors of lymph node metastasis (P < 0.001, respectively). Lymph node metastasis was not found in any patient with undifferentiated EGC smaller than 2.5 cm confined to the mucosa or upper third of the submucosal layer without lymphatic involvement.
CONCLUSIONS Undifferentiated intramucosal EGC smaller than 2.5 cm without lymphatic involvement was not associated with lymph node metastasis. Thus, we propose in this circumstance that endoscopic mucosal resection could be considered a definitive treatment without compromising the possibility of cure.
PubMed IF 3.5 소화기내과
2972008

제1저자 방지환 · 교신저자 김남중

, , , , , , , , ,
Prevalence of primary antiretroviral resistance: trends in Korea.
AIDS Res Hum Retroviruses. 2008;24(1):83-5.

Abstract
Primary drug resistance is an emerging problem in HIV infections. We have investigated the current prevalence of primary resistance in Korea and compared it with previous data. Drug-naive HIV patients attending the outpatient clinic of Seoul National University Hospital between April and August 2006 were enrolled. A medical interview and a genotypic resistance test were performed for each patient. The International AIDS Society-USA Panel consensus statement issued in 2006 was used to define resistance mutations. Eighty-one drug-naive HIV patients were enrolled. Two (2.5%) were infected with primary drug-resistant virus: M41L and K103N, respectively. In our previous study, conducted between 1998 and 2002, three (6%) of 50 subjects harbored resistant viruses. Thus the frequency of primary resistance was lower in the present sample than in the earlier one, though the difference is not statistically significant (p = 0.37). In view of our findings, routine antiretroviral resistance tests for drug-naive HIV patients are not obligatory in Korea.
PubMed IF 1 감염내과
2962008

제1저자 이해영 · 교신저자 김효수

, , , , , , , , , ,
FOXO3a turns the tumor necrosis factor receptor signaling towards apoptosis through reciprocal regulation of c-Jun N-terminal kinase and NF-kappaB.
Arterioscler Thromb Vasc Biol. 2008;28(1):112-20.

Abstract
OBJECTIVE We evaluated the full range effects of FOXO3a in endothelial cells (ECs) by microarray analysis and investigated the role of FOXO3a regulating TNF receptor signaling pathway.
METHODS AND RESULTS Human umbilical vein endothelial cells (HUVECs) were transfected with adenoviral vectors expressing constitutively active FOXO3a (Ad-TM-FOXO3a). Ad-TM-FOXO3a transfection caused remarkable apoptosis, which were accompanied with upregulation of genes related with TNF receptor signaling, such as TNF-alpha, TANK (TRAF-associated NF-kappaB activator), and TTRAP (TRAF and TNF receptor-associated protein). Furthermore, kappaB-Ras1 (IkappaB-interacting Ras-like protein-1) which is known to block IkappaB degradation was found increased, and intranuclear translocation of NF-kappaB was inhibited. GADD45beta and XIAP, negative regulators of c-Jun N-terminal kinase (JNK), were suppressed and JNK activity was increased. Attenuation of TNF signaling pathway either by blocking antibody for TNF receptor or by blocking JNK with DMAP (6-dimethylaminopurine) or Ad-TAM67 (dominant negative c-Jun) cotransfection, significantly reduced FOXO3a-induced apoptosis. Finally, treatment of vasculature with heat shock, an activator of endogenous FOXO3a, resulted in EC apoptosis, which was completely rescued by Ad-TAM67.
CONCLUSIONS FOXO3a promotes apoptosis of ECs, through activation of JNK and suppression of NF-kappaB. These data identify a novel role of FOXO3a to turn TNF receptor signaling to a proapoptotic JNK-dependent pathway.
PubMed IF 8.8 순환기내과
2952008

제1저자 김선영 · 교신저자 방영주

, , , , , , , ,
Trastuzumab inhibits the growth of human gastric cancer cell lines with HER2 amplification synergistically with cisplatin.
Int J Oncol. 2008;32(1):89-95.

Abstract
HER2 has been found to be amplified in 10-20% of gastric cancers, and is correlated with poor outcome. The aims of this study were to recognize HER2 amplification in gastric cancer cell lines via fluorescence in situ hybridization and to evaluate the growth inhibitory effect of trastuzumab in HER2-amplified cell lines. To elucidate the mechanism of the growth inhibition, we performed cell cycle analysis and immunoblotting of downstream molecules. We also conducted drug interaction studies of trastuzumab with other chemotherapeutic agents. HER2 amplification was newly identified only in SNU-216 cells, and trastuzumab moderately inhibited the growth of SNU-216 cells and positive controls. Trastuzumab-mediated G1 arrest occurred with increased expression of p27(KIP1) and decreased cyclins. Phosphorylation of HER2 and downstream molecules, STAT3, AKT, and ERK, was also inhibited by trastuzumab. Treatment of SNU-216 cells with trastuzumab plus cisplatin resulted in a synergistic inhibitory effect, whereas treatment of SNU-216 cells with trastuzumab plus 5-FU, or trastuzumab plus oxaliplatin produced an additive effect. These results suggest that trastuzumab combined with chemotherapeutic agents can be active against gastric cancer with HER2 amplification.
PubMed IF 7.3 혈액종양내과
2942008

제1저자 우상명 · 교신저자 류지곤

, , , , , ,
Survival and prognosis of invasive intraductal papillary mucinous neoplasms of the pancreas: comparison with pancreatic ductal adenocarcinoma.
Pancreas. 2008;36(1):50-5.

Abstract
OBJECTIVES Invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas is often considered to have a better prognosis than pancreatic ductal adenocarcinoma. The aim of this study was to evaluate and compare the prognosis and clinicopathologic features between 2 groups.
METHODS Clinicopathologic features and long-term outcome of 32 patients with invasive IPMN were retrospectively evaluated and compared with those of 332 patients with pancreatic ductal adenocarcinoma.
RESULTS Asymptomatic patients were more frequently observed in the group of invasive IPMN than ductal adenocarcinoma (28% vs 11%, P = 0.013). The distribution of stages of invasive IPMN was as follows: stage I (n = 10, 31%), II (n = 8, 25%), III (n = 3, 9%), and IV (n = 11, 34%). Among 19 patients who underwent resection for invasive IPMN, 10 (53%), 1 (5%), 1 (5%), and 2 (11%) had T1 stage tumors and tumor with lymph node metastasis, lymphatic, and perineural invasions, respectively, which were significantly infrequently observed compared with those with ductal adenocarcinoma. The 5-year survival rate of invasive IPMN was 33.9% compared with 9% of ductal adenocarcinoma (P = 0.011). The difference in the mean survival rates between invasive IPMN and ductal adenocarcinoma in patients without metastasis was also significant but not in patients with metastasis. During the median follow-up period of 18.4 months, 3 patients (16%) had a recurrence after resection for invasive IPMN.
CONCLUSIONS Both the less aggressive pathological factors concerned with tumor invasiveness and early diagnosis of invasive IPMN contribute to higher survival rates of invasive IPMN than ductal adenocarcinoma. However, the prognosis of metastatic invasive IPMN is as poor as that of ductal adenocarcinoma.
PubMed IF 2.2 소화기내과
2932008

제1저자 강형민 · 교신저자 김나영

, , , , , , , , ,
Effects of Helicobacter pylori Infection on gastric mucin expression.
J Clin Gastroenterol. 2008;42(1):29-35.

Abstract
AIMS This study was performed to determine the gastric distributions of MUC5AC and MUC6 depending on Helicobacter pylori (H. pylori) infection, and to evaluate whether the expressions of MUC5 and MUC6 change in H. pylori-associated gastroduodenal diseases. In addition, MUC5AC and MUC6 expressional changes were investigated before and after H. pylori eradication.
METHODS In the 224 individuals (136 H. pylori-positive and 88 H. pylori-negative) who came from control (N=48), duodenal ulcer (N=35), benign gastric ulcer (N=61), dysplasia plus stomach cancer (N=80) groups, MUC5AC and MUC6 expressions were determined by immunohistochemical staining in the antrum and body, respectively. This staining for MUC5AC and MUC6 were reperformed in 113 of the 136 H. pylori-positive patients after successful H. pylori eradication by proton pump inhibitor-based triple therapy.
RESULTS (1) No difference was found between the H. pylori-positive and negative groups in terms of MUC5AC expression. In contrast, MUC6 expression was significantly lower in the H. pylori-positive group than in the H. pylori-negative group in the gastric body. Moreover, reduced MUC6 expression increased to the H. pylori-negative level after eradication. (2) Expressions of MUC5AC and MUC6 were significantly lower in the dysplasia plus cancer group than those of control in case of H. pylori positive. Similarly, MUC5AC and MUC6 expressions were significantly lower in the presence of atrophic gastritis with intestinal metaplasia in case of H. pylori positive. (3) Aberrant expressions of MUC6 in foveolar cells were observed in both antrum (11.3%) and body (5.3%) only in the H. pylori-positive group, but this reverted to normal after H. pylori eradication.
CONCLUSION These results suggest that H. pylori infection causes alterations of mucin expression, closely related with the development of gastric atrophy with intestinal metaplasia, probably contributing to carcinogenesis.
PubMed IF 2.7 소화기내과
2922008

제1저자 김나영 · 교신저자 김나영

, , , , , , , , ,
Helicobacter pylori infection and development of gastric cancer in Korea: long-term follow-up.
J Clin Gastroenterol. 2008;42(5):448-54.

Abstract
BACKGROUND AND AIM Infection of Helicobacter pylori is viewed as a major driver of progression to the precancerous state or to gastric cancer. This study was performed to investigate the effect of H. pylori infection on gastric cancer development and to determine to what extent H. pylori eradication is likely to reduce the prevalence of gastric cancer.
METHODS Gastric cancer development was investigated in 1790 Korean subjects who underwent gastroscopy and H. pylori testing between 1992 and 1998. The effects of H. pylori-positive and eradicated states on gastric cancer development were analyzed.
RESULTS Gastric cancer developed in 5 of the study cohort during a mean follow-up period of 9.4 years. All of these patients were positive for H. pylori infection, and 4 of the 5 had antral intestinal metaplasia (IM) at the time of study enrollment. One of these 5 patients was in an eradicated state when the gastric cancer was diagnosed, and had histologic IM before eradication therapy was performed. Gastric cancer was found to develop 10.9 times more frequently in the presence of IM than in its absence.
CONCLUSIONS The present study shows a close relationship between H. pylori infection and IM, and between IM and the development of gastric cancer. In addition, our finding suggests that chronic H. pylori infection looks like an important risk factor for the development of gastric cancer in Korea, where the prevalence of H. pylori remains high. This study indicates that to prevent gastric cancer H. pylori eradication is best performed before the development of IM.
PubMed IF 2.7 소화기내과
2912008

제1저자 최인호 · 교신저자 김재영,안규리

, , , , , , , , ,
Xenogeneic interaction between human CD40L and porcine CD40 activates porcine endothelial cells through NF-kappaB signaling.
Mol Immunol. 2008;45(2):575-80.

Abstract
Xenotransplantation is a promising alternative to overcome donor shortage in transplantation. CD40 molecule plays an important role in the interaction of T cells with antigen-presenting cells and in the activation of vascular endothelial cells. We investigated whether the xenogeneic interaction between human CD40L (hCD40L) on T cells and porcine endothelial CD40 (pCD40) can activate porcine endothelial cells (PECs). The interaction between hCD40L and pCD40 induced the expression of chemokines on PECs as well as MHC and adhesion molecules. Furthermore, NF-kappaB signaling was activated in HEK 293 cells expressing pCD40 and PECs by stimulation with hCD40L+ Jurkat T clones. Both anti-CD40L neutralizing antibodies and NF-kappaB signal inhibitors interfered with immune activation of PECs. Overall, this study shows that xenogeneic interaction between hCD40L and pCD40 can activate PECs through NF-kappaB signaling, and therefore may contribute to acute vascular rejection in xenotransplantation.
PubMed IF 3.7 신장내과
2902008

제1저자 김성한 · 교신저자 오명돈

, , , , , ,
Outcome of vancomycin treatment in patients with methicillin-susceptible Staphylococcus aureus bacteremia.
Antimicrob Agents Chemother. 2008;52(1):192-7.

Abstract
Limited data on the clinical outcome of vancomycin treatment compared with that of beta-lactam treatment in patients with methicillin-susceptible Staphylococcus aureus bacteremia (MSSA-B) are available. We used different and complementary approaches: (i) a retrospective cohort study using a propensity score to adjust for confounding by treatment assignment and (ii) a matched case-control study. Of all patients with S. aureus bacteremia (SAB) in two university-affiliated hospitals over a 7-year period, 294 patients with MSSA-B were enrolled in the cohort study. The cases for the case-control study were defined as patients who received vancomycin treatment for MSSA-B; the controls, who were patients that received beta-lactam treatment for MSSA-B, were selected at a 1:2 (case:control) ratio according to the objective matching scoring system and the propensity score system. In the cohort study, SAB-related mortality in patients with vancomycin treatment (37%, 10/27) was significantly higher than that in those with beta-lactam treatment (18%, 47/267) (P = 0.02). In addition, multivariate analysis revealed that vancomycin treatment was associated with SAB-related mortality when independent predictors for SAB-related mortality and propensity score were considered (adjusted odds ratio of 3.3, 95% confidence interval of 1.2 to 9.5). In the case-control study using the objective matching scoring system and the propensity score system, SAB-related mortality in case patients was 37% (10/27) and in control patients 11% (6/54) (P < 0.01). Our data suggest that vancomycin is inferior to beta-lactam in the treatment of MSSA-B.
PubMed IF 4.2 감염내과
2892008

제1저자 이상협 · 교신저자 이동호

, , , , , , , , , , , ,
Submucosal saline-epinephrine injection in colon polypectomy: appropriate indication.
Hepatogastroenterology. 2008;55(86-87):1589-93.

Abstract
BACKGROUND/AIMS Opinions vary among endoscopists concerning the indications for submucosal saline-epinephrine injection for the prevention of postpolypectomy complications after colonic snare polypectomy. This study was performed to determine the appropriate indications for submucosal saline-epinephrine injection.
METHODOLOGY Clinical characteristics and complications (hemorrhage and perforation) in polypectomies were retrospectively evaluated. Postpolypectomy complications were analyzed in terms of demographic characteristics (age, gender), polyp characteristics (size, configuration, location, and histopathology), and the administration of submucosal saline-epinephrine injection.
RESULTS Total 1039 polypectomies were performed in 563 patients (age 59.8 +/- 10.1 years), and submucosal saline-epinephrine injection was performed in 679 polypectomies. Twenty seven episodes (2.6%) of hemorrhage and 3 cases (0.2%) of perforation occurred. Malignant adenoma, a rectal polyp, and procedure without submucosal saline-epinephrine injection increased the risk of hemorrhage with odds ratios of 10.48, 4.71, and 3.44, respectively. Furthermore, submucosal saline-epinephrine injection significantly reduced the risk of hemorrhage in sessile polyps and those > 8 mm in size and with odds ratio of 16.41 regardless of location or histopathology. The occurrence of postpolypectomy perforation was not associated with any clinical characteristics and method.
CONCLUSIONS Submucosal saline-epinephrine injection should be performed for sessile polyps and those > 8 mm in size, and might be performed optionally in other cases to prevent postpolypectomy hemorrhage.
PubMed IF 0.904 소화기내과
2882008

제1저자 이상협 · 교신저자 황진혁

, , , , , , , , , ,
Does endoscopic sphincterotomy reduce the recurrence rate of cholangitis in patients with cholangitis and suspected of a common bile duct stone not detected by ERCP?
Gastrointest Endosc. 2008;67(1):51-7.

Abstract
BACKGROUND It has not been established whether endoscopic sphincterotomy (ES) prevents subsequent cholangitis in patients with cholangitis and with a common bile duct (CBD) stone not documented by ERCP.
OBJECTIVE The aim of this study was to investigate the role of ES on the recurrence of cholangitis in patients with a high probability of having a CBD stone, not demonstrated by ERCP.
DESIGN AND PATIENTS A total of 117 patients who were diagnosed as having cholangitis and a high probability of a CBD stone, not detected by ERCP, were retrospectively reviewed. Cumulative recurrence rates of cholangitis were compared for treatments with and without ES.
SETTING Multicenter, retrospective study.
INTERVENTIONS ES.
MAIN OUTCOME MEASUREMENTS Cumulative recurrence of cholangitis after ERCP.
RESULTS Eighty-three patients underwent ES (ES group) and 34 patients did not (non-ES group). No statistically significant differences between the 2 groups were evident in terms of demographic factors or laboratory findings. The mean (standard deviation) follow-up was 22.1 +/- 17.2 months (range 3-66 months) in the ES group and 23.3 +/- 14.9 months (range 6-84 months) in the non-ES group (P = .72). The cumulative rates of cholangitis were 6.3% (4.8% vs 9.9%) at 1 year, 15.6% (9.2% vs 29.3%) at 3 years, and 19.5% (9.2% vs 52.9%) at 5 years for ES vs non-ES groups, respectively (P = .04). By multivariate analysis, ES reduced cholangitis recurrence, with a hazard ratio of 0.305 (95% CI 0.095-0.975, P = .045).
LIMITATIONS Retrospective study.
CONCLUSIONS ES reduced further episodes of cholangitis in patients with an episode of cholangitis and a high probability of choledocholithiasis, despite the lack of a CBD stone seen on ERCP.
PubMed IF 8 소화기내과
2872008

제1저자 박정현 · 교신저자 김태유

, , , , , , , ,
Inhibitors of histone deacetylases induce tumor-selective cytotoxicity through modulating Aurora-A kinase.
J Mol Med (Berl). 2008;86(1):117-28.

Abstract
The molecular basis of the antitumor selectivity of histone deacetylase inhibitors (HDIs) remains unclear. Centrosomal Aurora-A kinase regulates chromosomal segregation during mitosis. The overexpression or amplification of Aurora-A leads to genetic instability, and its inhibition has shown significant antitumor effects. In this paper, we report that structurally related hydroxamate LAQ824 and SK-7068 induce tumor-selective mitotic defects by depleting Aurora-A. We found that HDI-treated cancer cells, unlike nontransformed cells, exhibit defective mitotic spindles. After HDI, Aurora-A was selectively downregulated in cancer cells, whereas Aurora-B remained unchanged in both cancer and nontransformed cells. LAQ824 or SK-7068 treatment inhibited histone deacetylase (HDAC) 6 present in Aurora-A/heat shock protein (Hsp) 90 complex. Inhibition of HDAC6 acetylated Hsp90 and resulted in dissociation of acetylated Hsp90 from Aurora-A. As a result, Hsp70 binding to Aurora-A was enhanced in cancer cells, leading to proteasomal degradation of Aurora-A. Overall, these provide a novel molecular basis of tumor selectivity of HDI. LAQ824 and SK-7068 might be more effective HDIs in cancer cells with Aurora-A overexpression.
PubMed IF 5 혈액종양내과
2862007

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
2852007

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
2842007

제1저자 윤영호 · 교신저자 허대석

, , , , , , , , , ,
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
2832007

제1저자 김광일 · 교신저자 김철호

, , , , , , , , , ,
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
2822007

제1저자 오일영 · 교신저자 김효수,박영배

, , , , , , , , , ,
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
2812007

제1저자 강정묵 · 교신저자 김나영

, , , , , , ,
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
2802007

제1저자 김경원 · 교신저자 조보연

, , , , ,
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
2792007

제1저자 김동완 · 교신저자 허대석

, , , , , , , ,
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
2782007

제1저자 이석묵 · 교신저자 안규리

, , , , , , , , , ,
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
2772007

제1저자 오윤규 · 교신저자 나기영

, , , , , , ,
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
2762007

제1저자 김형관 · 교신저자 김용진

, , , , , , , , , ,
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
2752007

제1저자 박병래 · 교신저자 이효석

, , , , , , , , , ,
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
2742007

제1저자 김혜련 · 교신저자 임재준

, , , , , , , ,
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
2732007

제1저자 김성한 · 교신저자 오명돈

, , , , ,
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
2722007

제1저자 이계숙 · 교신저자 안규리

, , , , , , , , , , , , , ,
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
2712007

제1저자 우상명 · 교신저자 류지곤

, , , , , , , , ,
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
2702007

제1저자 박흥우 · 교신저자 조상헌

, , , , , , , , ,
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
2692007

제1저자 조영민,김진택 · 교신저자 박경수

, , , , , , ,
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

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