SCI 발표논문
2006년 77편
- 472006
제1저자 오세일 · 교신저자 최윤식
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Atypical atrioventricular nodal reentrant tachycardia in a patient with fasciculoventricular pathway.Heart Rhythm. 2006;3(9):1085-7.
- 462006
제1저자 권동아 · 교신저자 손대원
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Prediction of outcome in patients undergoing surgery for severe tricuspid regurgitation following mitral valve surgery and role of tricuspid annular systolic velocity.Am J Cardiol. 2006;98(5):659-61.
PubMed IF 2.5 순환기내과Abstract
This study was performed to identify echocardiographic parameters related to postoperative clinical outcome in patients who undergo surgery for severe tricuspid regurgitation after mitral valve surgery. Eighteen patients (2 men, 16 women; mean age 58 years) were prospectively enrolled. Echocardiographic examinations were performed before and 15 +/- 7 months after surgery. Favorable postoperative clinical outcome was defined as an improvement of > or = 1 in New York Heart Association functional class or a > 25% increase in respiratory variation of inferior vena cava diameter. Operative mortality was 11% (2 of 18). Of the 16 survivors, 9 (56%) achieved favorable postoperative clinical outcomes. Only systolic tricuspid annulus velocity (S'T) was found to be associated with postoperative clinical outcome (favorable vs unfavorable postoperative clinical outcome 12.9 +/- 2.1 vs 9.7+/- 1.7 cm/s, p < 0.05). For S'T < 9.5 cm/s, the sensitivity, specificity, and positive and negative predictive values for predicting an unfavorable postoperative clinical outcome were 67%, 100%, 100%, and 75%, respectively. In conclusion, S(T') can predict postoperative clinical outcomes in these patients.
- 452006
제1저자 김성한 · 교신저자 오명돈
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Prediction of residual immunity to smallpox, by means of an intradermal skin test with inactivated vaccinia virus.J Infect Dis. 2006;194(3):377-84.
PubMed IF 4.1 감염내과Abstract
BACKGROUND Intradermal skin testing with inactivated vaccinia virus was evaluated for its prediction of residual immunity to smallpox.
METHODS An intradermal skin test was performed with heat-inactivated Lancy-Vaxina. Two days later, the subjects were vaccinated with Lancy-Vaxina. The skin lesions resulting from this vaccination were used as a surrogate marker of residual immunity to smallpox, and this surrogate marker was compared with the available indicators of susceptibility to smallpox.
RESULTS Of the 83 subjects, 30 (36%) showed the typical primary response after vaccination (i.e., absence of residual immunity), whereas 34 (41%) showed the typical revaccinee's response (i.e., presence of residual immunity); the remaining 19 (23%) had an indeterminate response and were excluded from the final analysis. The sensitivity and specificity of the intradermal skin test (induration size, >or=4 mm) for prediction of residual immunity to smallpox were 85% and 97%, respectively, whereas those of a positive vaccinia-specific interferon- gamma -producing T cell response (>or=9 spot forming cells/10(6) peripheral-blood mononuclear cells) were 32% and 63%, respectively, and those of a positive neutralizing antibody (titer, >or=1 : 8) were 79% and 80%, respectively.
CONCLUSION The intradermal skin test appears to be a simple and reliable method for prediction of residual immunity to smallpox.
- 442006
제1저자 김강모 · 교신저자 윤정환
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Eupatilin attenuates bile acid-induced hepatocyte apoptosis.J Gastroenterol. 2006;41(8):772-8.
PubMed IF 5.7 소화기내과Abstract
BACKGROUND In cases of cholestasis, bile acids induce hepatocyte apoptosis by activating death receptor-mediated apoptotic signaling cascades. Eupatilin (5,7-dihydroxy-3,4,6-trimethoxyflavone) is a pharmacologically active ingredient found in Artemisia asiatica and exhibits cytoprotective effects against experimentally induced gastrointestinal, pancreatic, and hepatic damage. This study was undertaken to examine if eupatilin modulates bile acid-induced hepatocyte apoptosis.
METHODS Huh-BAT cells, a human hepatocellular carcinoma cell line stably transfected with a bile acid transporter, were used in this study. Apoptosis was quantified using 4',6-diamidino-2-phenylindole dihydrochloride staining, and its signaling cascades were explored by immunoblot analysis. Kinase signaling was evaluated by immunoblotting and by using selective inhibitors. Eupatilin's in vivo effect on bile acid-induced hepatocyte apoptosis was explored in bile duct-ligated rats.
RESULTS Eupatilin significantly reduced bile acid-mediated hepatocyte apoptosis by attenuating bile acid-induced caspase 8 cleavage. Eupatilin diminished the bile acid-induced activation of mitogen-activated protein kinases, including p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. In particular, the eupatilin-mediated inhibition of bile acid-induced c-Jun N-terminal kinase activation was found to be responsible for attenuating caspase 8 cleavage. Moreover, eupatilin diminished hepatocyte apoptosis in bile duct-ligated rats.
CONCLUSIONS Eupatilin attenuates bile acid-induced hepatocyte apoptosis by suppressing bile acid-induced kinase activation. Therefore, eupatilin might be therapeutically efficacious in a variety of human liver diseases associated with cholestasis.
- 432006
제1저자 김태유 · 교신저자 K. Robertson
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Epigenomic profiling reveals novel and frequent targets of aberrant DNA methylation-mediated silencing in malignant glioma.Cancer Res. 2006;66(15):7490-501.
PubMed IF 22.6 혈액종양내과Abstract
Malignant glioma is the most common central nervous system tumor of adults and is associated with a significant degree of morbidity and mortality. Gliomas are highly invasive and respond poorly to conventional treatments. Gliomas, like other tumor types, arise from a complex and poorly understood sequence of genetic and epigenetic alterations. Epigenetic alterations leading to gene silencing, in the form of aberrant CpG island promoter hypermethylation and histone deacetylation, have not been thoroughly investigated in brain tumors, and elucidating such changes is likely to enhance our understanding of their etiology and provide new treatment options. We used a combined approach of pharmacologic inhibition of DNA methylation and histone deacetylation, coupled with expression microarrays, to identify novel targets of epigenetic silencing in glioma cell lines. From this analysis, we identified >160 genes up-regulated by 5-aza-2'-deoxycytidine and trichostatin A treatment. Further characterization of 10 of these genes, including the putative metastasis suppressor CST6, the apoptosis-inducer BIK, and TSPYL5, whose function is unknown, revealed that they are frequent targets of epigenetic silencing in glioma cell lines and primary tumors and suppress glioma cell growth in culture. Furthermore, we show that other members of the TSPYL gene family are epigenetically silenced in gliomas and dissect the contribution of individual DNA methyltransferases to the aberrant promoter hypermethylation events. These studies, therefore, lay the foundation for a comprehensive understanding of the full extent of epigenetic changes in gliomas and how they may be exploited for therapeutic purposes.
- 422006
제1저자 장혜련 · 교신저자 한진석
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From bench to bedside: diagnosis of Gitelman's syndrome -- defect of sodium-chloride cotransporter in renal tissue.Kidney Int. 2006;70(4):813-7.
- 412006
제1저자 김윤준 · 교신저자 이효석
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IGF2 polymorphisms are associated with hepatitis B virus clearance and hepatocellular carcinoma.Biochem Biophys Res Commun. 2006;346(1):38-44.
PubMed IF 2.5 소화기내과Abstract
The aim of this study was to determine whether IGF2 polymorphisms are associated with the clearance of hepatitis B virus (HBV) infection and the risk of hepatocellular carcinoma (HCC). A total of 1095 Korean subjects were prospectively enrolled in this case-control study. The rates of IGF2 polymorphisms were determined in each group. The IGF2+820G allele (IGF2+820G/G) and the IGF2+6815A/A genotype were strongly associated with the resolution of HBV infection (OR=0.62-0.73; P=0.001-0.03 and OR=0.71; P=0.03, respectively). Haplotype analysis showed that IGF2-haplotype5 (A-C-C-T-A-T-G) and IGF2-haplotype1 (T-C-T-T-A-C-A) were significantly associated with the clearance and persistence of HBV infection (OR=0.55-0.58, P=0.009-0.01 and OR=1.31-1.65, P=0.001-0.007, respectively). On the other hand, the IGF2+2482C/C or +820G/G genotypes were significantly associated with a higher risk of HCC (OR=1.88, 1.68; P=0.04). IGF2 polymorphisms were found to be strongly associated with the clearance of HBV or the occurrence of HCC in patients with chronic HBV infection.
- 402006
제1저자 조현재 · 교신저자 김효수
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The effect of stem cell mobilization by granulocyte-colony stimulating factor on neointimal hyperplasia and endothelial healing after vascular injury with bare-metal versus paclitaxel-eluting stents.J Am Coll Cardiol. 2006;48(2):366-74.
PubMed IF 22.3 순환기내과Abstract
OBJECTIVES The goal of this study was to investigate the effect of mobilized stem cells by granulocyte-colony stimulating factor (G-CSF) on neointimal growth, the biologic impact on vascular healing process, and the utility of paclitaxel-eluting stent (PES) in this circumstance.
BACKGROUND Questions have been raised on the safety of stem cell mobilization because of the tendency of neointimal overgrowth in a recent clinical trial, despite improvement of cardiac function.
METHODS Rabbits underwent iliac artery injury with bare-metal stent (BMS) or PES and then received rhG-CSF or placebo for 6 days. Morphometric analysis and scanning electron microscopy for re-endothelialization were performed. The characteristics of mobilized peripheral blood mononuclear cells were determined in vitro, and the fate of these cells was evaluated by re-infusion with tagging in vivo.
RESULTS At day 60 after stenting, neointimal overgrowth was observed at BMS with G-CSF. The tendency of neointimal overgrowth was substantially reduced on PES. Intriguingly, the delayed endothelial recovery on PES was restored to normal after G-CSF treatment. The G-CSF increased not only the endothelial progenitor cells, but also putative smooth muscle progenitor cells. Paclitaxel, at working concentration, preferentially inhibited proliferation of smooth muscle lineage cells rather than endothelial lineage cells.
CONCLUSIONS Our findings demonstrate that G-CSF mobilizes putative vascular progenitor cells in peripheral blood, which induces neointimal overgrowth at stented vasculature. Unique differential action of paclitaxel results in the enhanced endothelial healing with reduced neointimal growth after G-CSF treatment, suggesting that drug-eluting stents might be the optimal modality for revascularization in cytokine-based stem cell therapy.
- 392006
제1저자 이경훈 · 교신저자 허대석
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High fluorodeoxyglucose uptake on positron emission tomography in patients with advanced non-small cell lung cancer on platinum-based combination chemotherapy.Clin Cancer Res. 2006;12(14 Pt 1):4232-6.
PubMed IF 10.9 혈액종양내과Abstract
PURPOSE To evaluate response and survival for platinum-based combination chemotherapy in chemonaive patients with non-small cell lung cancer (NSCLC) according to pretreatment standardized uptake values (SUV) by fluorodeoxyglucose positron emission tomography.
EXPERIMENTAL DESIGN Patients with advanced NSCLC who had not previously received chemotherapy were eligible. Response rates and survivals were analyzed according to maximal SUVs [low (<or=7.5) versus high (>7.5), where 7.5 was the median value] before the first cycle of chemotherapy.
RESULTS Eighty-five consecutive patients were included in the retrospective study. Patients with high SUV tumors exhibited significantly higher response rates (34.1% for low SUVs versus 61.0% for high SUVs; P = 0.013). Other factors, including sex, age, histology, performance status, number of involved organs, regimens used, and disease stage, did not affect response. However, high SUVs were related with a shorter response duration (279 days for low SUVs versus 141 days for high SUVs; P = 0.003) and time to progression (282 days for low SUVs versus 169 days for high SUVs; P = 0.015). Overall survival was unaffected by maximal SUVs (623 days for low SUVs versus 464 days for high SUVs; P = 0.431).
CONCLUSIONS Patients having NSCLC with high maximal SUVs showed a better response to platinum-based combination chemotherapy but had a shorter time to progression. Tumor glucose metabolism, as determined by SUVs on fluorodeoxyglucose positron emission tomography, was found to discriminate NSCLC subsets with different clinical and biological features.
- 382006
제1저자 김형관 · 교신저자 김용진
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Determinants of the severity of functional tricuspid regurgitation.Am J Cardiol. 2006;98(2):236-42.
PubMed IF 2.5 순환기내과Abstract
We performed a prospective study of patients with chronic right ventricular (RV) dilation to determine the factors associated with the degree of functional tricuspid regurgitation (FTR). We prospectively enrolled 64 patients with chronic RV dilation and measured right atrial (RA) area, RV area and its fractional area change (RVFAC), tricuspid annular diameter and contraction, tricuspid valve (TV) tethering area, and systolic pulmonary artery pressure. We also measured the RV eccentricity index and the RV sphericity index for simple presentation of RV geometry. Regurgitant orifice area of FTR was obtained for the quantification of FTR. End-systolic RV eccentricity index (r=0.73), end-diastolic RV eccentricity index (r=0.56), RA area (r=0.49), TV tethering area (r=0.37), age (r=0.31), end-systolic (r=0.42) and end-diastolic (r=0.30) tricuspid annular diameters, and left ventricular ejection fraction (r=-0.37) were significantly related to the regurgitant orifice area of FTR in univariate analysis. However, RV area, RVFAC, and systolic pulmonary artery pressure were not. In multivariate analysis, the end-systolic RV eccentricity index (p<0.001), TV tethering area (p=0.003), and end-diastolic tricuspid annulus diameter (p=0.007) showed the independent associations with regurgitant orifice area of FTR. The sensitivities and specificities for predicting more than mild FTR were found to be 79% and 82% with an end-systolic RV eccentricity index>2.0, 69% and 73% with an end-systolic tethering area>1.0 cm2, and 64% and 59% for an end-systolic tricuspid annulus diameter>3.9 cm, respectively. FTR severity was found to show the best correlation with the end-systolic RV eccentricity index. In conclusion, these findings underscore the importance of eccentric RV dilation for determining FTR severity and should lead to the development of more rational surgical approaches to FTR beyond TV annuloplasty.
- 372006
제1저자 이승표 · 교신저자 김효수/박영배
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Integrin-linked kinase, a hypoxia-responsive molecule, controls postnatal vasculogenesis by recruitment of endothelial progenitor cells to ischemic tissue.Circulation. 2006;114(2):150-9.
PubMed IF 41.3 순환기내과Abstract
BACKGROUND Recruitment and adhesion of endothelial progenitor cells (EPCs) to hypoxic endothelial cells (ECs) is essential for vasculogenesis in ischemic tissue; little is known, however, about the key signals or intracellular signaling pathways involved in orchestrating the expression of adhesion molecules by ECs in response to hypoxia and how this is related to the recruitment of EPCs to the ischemic tissue. Here, we report that endogenous integrin-linked kinase (ILK) is a novel molecule that responds to hypoxia in ECs that regulates the expression of stromal cell-derived factor-1 (SDF-1) and intercellular adhesion molecule-1 (ICAM-1) through nuclear factor-kappaB and hypoxia-inducible factor-1alpha and induces recruitment of EPCs to ischemic areas.
METHODS AND RESULTS Under hypoxia, both the endogenous amount and kinase activity of ILK were time-dependently upregulated in ECs, which was associated with increased ICAM-1 and SDF-1. This upregulation of ILK was mediated by stabilization of ILK by heat shock protein 90. ILK overexpression in normoxic ECs resulted in ICAM-1 and SDF-1 upregulation through dual control by nuclear factor-kappaB and hypoxia-inducible factor-1alpha. Blockade of ILK in hypoxic ECs significantly abrogated the expression of both molecules, which led to decreased EPC incorporation into ECs. A hindlimb ischemia model showed that ILK blockade significantly reduced EPC homing to ischemic limb and consequently led to poor neovascularization. Overexpression of ILK in the Matrigel plug significantly improved neovascularization in vivo, whereas the blockade of ILK resulted in the opposite effect.
CONCLUSIONS Endogenous ILK is a novel and physiological upstream responder of numerous intracellular molecules involved in hypoxic stress in ECs and may control the recruitment of EPCs to ischemic tissue.
- 362006
제1저자 강현재/이해영 · 교신저자 김효수/박영배
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Differential effect of intracoronary infusion of mobilized peripheral blood stem cells by granulocyte colony-stimulating factor on left ventricular function and remodeling in patients with acute myocardial infarction versus old myocardial infarction: the MAGIC Cell-3-DES randomized, controlled trial.Circulation. 2006;114(1 Suppl):I145-51.
PubMed IF 41.3 순환기내과Abstract
BACKGROUND The efficacy of intracoronary infusion of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSCs) has not been compared between patients with acute (AMI) versus old myocardial infarction (OMI). In addition, the potential risk of restenosis associated with G-CSF-based stem cell therapy has not been evaluated in the setting of drug eluting stent (DES) implantation.
METHODS AND RESULTS We randomly allocated 96 patients with myocardial infarction who underwent coronary revascularization with DES for the culprit lesion into 4 groups. Eighty-two patients completed 6-month follow-up; AMI cell infusion (n=25), AMI control (n=25), OMI cell infusion (n=16), and OMI control group (n=16). In cell infusion groups, PBSCs were mobilized by G-CSF for 3 days and delivered to infarcted myocardium via intracoronary infusion. The AMI cell infusion group showed a significant additive improvement in left ventricular ejection fraction (LVEF) and remodeling compared with controls (change of LVEF: +5.1+/-9.1% versus -0.2+/-8.6%, P<0.05; change of end-systolic volume: -5.4+/-17.0 mL versus 6.5+/-21.9 mL, P<0.05). In OMI patients, however, there was no significant change of LVEF and ventricular remodeling in spite of significant improvement of coronary flow reserve after cell infusion. G-CSF-based cell therapy did not aggravate neointimal growth with DES implantation.
CONCLUSIONS Intracoronary infusion of mobilized PBSCs with G-CSF improves LVEF and remodeling in patients with AMI but is less definite in patients with OMI. G-CSF-based stem cell therapy with DES implantation is both feasible and safe, eliminating any potential for restenosis.
- 352006
제1저자 고동석 · 교신저자 임재준
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Clinical implication of atypical cells from sputum in patients without lung cancer.Respirology. 2006;11(4):462-6.
PubMed IF 7.2 호흡기내과Abstract
OBJECTIVE AND BACKGROUND Atypical-but not definitely malignant-cells in cytological examinations of sputum are usually associated with lung cancers. However, atypical cells are occasionally identified in patients without lung cancer. The aim of this study was to determine the clinical implication of the atypical cells from sputum in patients without lung cancer or other malignancies.
METHODOLOGY All patients with atypical cells observed following cytological examination of sputum on one or more occasion over a 2-year period in Seoul National University Hospital were enrolled. After exclusion of patients followed up for less than 6 months, their clinical data were reviewed retrospectively.
RESULTS Among 601 enrolled patients with atypical cells, lung cancers were diagnosed within 30 days of identification of atypical cells in 542 (90.2%) patients. Five out of 59 patients who had no evidence of lung cancer, were subsequently diagnosed with lung cancer or other malignancies following a mean observation of 164 days. In the other 54 patients without subsequent malignancies, the most common respiratory diseases were pneumonia including tuberculosis.
CONCLUSIONS The subsequent development of malignancy in patients with atypical cells in sputum despite a thorough evaluation was rare, and close observation without invasive diagnostic procedures might be simply required in these patients.
- 342006
제1저자 이근욱 · 교신저자 허대석
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First-line ifosfamide, methotrexate, etoposide and prednisolone chemotherapy +/- radiotherapy is active in stage I/II extranodal NK/T-cell lymphoma.Leuk Lymphoma. 2006;47(7):1274-82.
PubMed IF 2.1 혈액종양내과Abstract
Although most patients diagnosed with extranodal NK/T-cell lymphoma (NTCL) have localized disease, radiotherapy alone is unsatisfactory because of frequent systemic failure and conventional doxorubicin-based chemotherapy has low efficacy. Twenty-six patients with NTCL received ifosfamide, methotrexate, etoposide and prednisolone (IMEP) chemotherapy as first-line treatment [ifosfamide 1.5 g/m2 (days 1 - 3), methotrexate 30 mg/m2 (days 3 and 10), etoposide 100 mg/m2 (days 1 - 3) and prednisolone 120 mg (days 1 - 5)]. Radiotherapy was administered only to patients with Ann Arbor stage I/II that had not achieved complete remission (CR) or to those that developed local failure after completing chemotherapy. Sixteen patients (group A) had nasal or upper aerodigestive tract localization (stage I/II) and 10 (group B) had extranasal or disseminated disease. Of the 14 evaluable patients in group A, 11 (79%) achieved CR after IMEP alone and 13 (93%) after chemotherapy +/- additional radiotherapy. Although, out of the 11 patients who achieved CR with chemotherapy alone, seven developed recurrence, all recurrences were local failure and successfully treated by additional curative radiotherapy. However, patients in group B responded poorly (CR 13%). IMEP regimen was active in NTCL patients with nasal or upper aerodigestive tract localization. Considering local failure rate after IMEP alone, initial IMEP chemotherapy followed by radiotherapy may be a promising treatment strategy in this subset of NTCL.
- 332006
제1저자 류지곤 · 교신저자 김용태
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SK-7041, a new histone deacetylase inhibitor, induces G2-M cell cycle arrest and apoptosis in pancreatic cancer cell lines.Cancer Lett. 2006;237(1):143-54.
PubMed IF 11.8 소화기내과Abstract
A novel hybrid synthetic histone deacetylase inhibitor, SK-7041, was synthesized from hydroaxamic acid of trichostatin A (TSA) and pyridyl ring of MS-275. TSA and SK-7041 both induced apoptosis and G2-M cell cycle arrest in pancreatic cancer cell lines. The expressions of p21 and cyclin D2 were up-regulated and that of cyclin B1 was down-regulated by TSA or SK-7041. The expression levels of Mcl-1 and Bcl-XL but not those of Bcl-2, Bax, and Bak were suppressed by TSA or SK-7041 treatment. SK-7041 or TSA induced apoptosis and G2-M cell cycle arrest by up-regulating p21 and down-regulating cyclin B1, Mcl-1, and Bcl-XL.
- 322006
제1저자 서정원,구본권 · 교신저자 김효수
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Increased risk of atherothrombotic events associated with cytochrome P450 3A5 polymorphism in patients taking clopidogrel.CMAJ. 2006;174(12):1715-22.
PubMed IF 8.6 순환기내과Abstract
BACKGROUND Clopidogrel is a prodrug requiring metabolism by cytochrome P450 3A (CYP3A) isoenzymes, including CYP3A5, in order to be active. It is controversial whether clopidogrel interacts with CYP3A inhibitors. We investigated the influence of CYP3A5 polymorphism on the drug interaction of clopidogrel.
METHODS In phase 1 of the study, we administered clopidogrel to 16 healthy volunteers who had the CYP3A5 non-expressor genotype (*3 allele) and 16 who had the CYP3A5 expressor genotype (*1 allele) with and without pretreatment with itraconazole, a potent CYP3A inhibitor. A platelet aggregation test was performed at baseline, 4 hours, 24 hours and 6 days after clopidogrel administration. In phase 2, we compared clinical outcomes of 348 patients treated with clopidogrel after successful coronary angioplasty with bare-metal stent implantation according to their CYP3A5 genotype; the primary end point was a composite of atherothrombotic events (cardiovascular death, myocardial infarction and non-hemorrhagic stroke) within 1 and 6 months after stent implantation.
RESULTS In phase 1, the change in platelet aggregation after clopidogrel administration and pretreatment with itraconazole was greater among the subjects with the CYP3A5 expressor genotype than among those with the non-expressor genotype: 24.9% (standard deviation [SD] 13.9%) v. 6.2% (SD 13.5%) at 4 hours (p < 0.001); 27.7% (SD 16.5%) v. 2.5% (SD 8.3%) at 24 hours (p < 0.001); and 33.5% (SD 18.6%) v. 17.8% (SD 13.8%) at day 7 (p < 0.01). In phase 2, atherothrombotic events occurred more frequently within 6 months after stent implantation among the patients with the non-expressor genotype than among those with the expressor genotype (14/193 v. 3/155; p = 0.023). Multivariable analysis showed that the CYP3A5 polymorphism was a predictor of atherothrombotic events in clopidogrel users.
INTERPRETATION People with the CYP3A5 non-expressor genotype are vulnerable to drug interactions between clopidogrel and CYP3A inhibitors. This phenomenon may be associated with worse outcomes in patients with the non-expressor genotype who are given clopidogrel after coronary angioplasty and implantation of bare-metal stents.
- 312006
제1저자 손대원 · 교신저자 손대원
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Assessment of coronary vasodilatation in response to nitroglycerin with transthoracic Doppler echocardiography.J Am Soc Echocardiogr. 2006;19(6):777-80.
PubMed IF 8.3 순환기내과Abstract
BACKGROUND Previous studies demonstrated impaired coronary vasodilatory response (VR) to nitroglycerin (NG) in patients with coronary atherosclerosis. We hypothesized that the effect of the NG on the coronary blood flow (CBF) is negligible compared with its effect on the epicardial coronary artery dilatation and, therefore, that CBF velocity reduction after NG can reflect the magnitude of epicardial coronary artery dilatation.
METHODS Quantitative coronary angiography was performed at the left anterior descending coronary artery (LAD) before and after intracoronary NG (200 mug) infusion in 18 patients with normal-looking coronary angiogram. VR assessed by quantitative coronary angiography (VRangio) was defined as: (LAD diameter after NG)(2)/(LAD diameter before NG)(2). Mean values measured at the ostium and at the junction of mid and distal LAD were used in the analysis. Diastolic CBF velocity was evaluated by using a 7-MHz transducer at the distal LAD before and 3 minutes after sublingual NG. VR assessed by echocardiography (VRecho) was defined as: (mean diastolic CBF velocity before sublingual NG)/(mean diastolic CBF velocity after sublingual NG). In 11 patients, plaque burden was assessed by intravascular ultrasound and results were compared with VRangio and VRecho.
RESULTS VRecho was found to correlate well with VRangio (r = 0.71, P = .001), and VRangio and VRecho showed significant negative correlations with plaque burden (r = -0.66, P = .03; r = -0.77, P = .005, respectively).
CONCLUSIONS VR to NG can be evaluated noninvasively with transthoracic Doppler echocardiography.
- 302006
제1저자 이은영, 임재준 · 교신저자 송영욱
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Dinucleotide repeat polymorphism in intron II of human Toll-like receptor 2 gene and susceptibility to rheumatoid arthritis.Int J Immunogenet. 2006;33(3):211-5.
PubMed IF 1.3 류마티스내과Abstract
Human Toll-like receptors (TLRs) participate in innate immune response and signal the activation of adaptive immunity. The presence of a functional intronic polymorphism consisting of guanine-thymine repeats in TLR2 gene was recently reported. Here, we investigated a dinucleotide repeat polymorphism in intron II of TLR2 in Korean patients with rheumatoid arthritis (RA). The numbers of guanine-thymine [(GT)(n)] repeats in intron II of the TLR 2 gene were counted in 183 patients with RA and in 148 healthy controls, using the gene scanning technique. We classified alleles into two subclasses for further analysis, 12-16 GT repeats (S allele) and 17-28 repeats (L allele). By subgroup analysis, we also examined whether the S allele is associated with the presence of shared epitope (SE), rheumatoid factor (RF), joint erosion and extra-articular complications. S-allele frequency was significantly increased in patients with RA than in healthy controls [30.3% vs. 23.0%, P = 0.03, or 1.46, 95% confidence interval (CI) 1.03-2.07], and genotypes containing S alleles were more frequent in patients with RA than in healthy controls (54.4% vs. 46.5%. P = 0.04, or 1.57, 95% CI 1.01-2.42). A skewed S-allele distribution was not found to be related to the presence of SE. Subgroup analysis showed no genotypic or allele frequency differences between patients with/without RF, joint erosion, or extra-articular complications. Genotype containing shorter GT repeats in intron II of the TLR2 gene may confer susceptibility to RA in Koreans.
- 292006
제1저자 이경훈 · 교신저자 김동완
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Epidermal growth factor receptor mutations and response to chemotherapy in patients with non-small-cell lung cancer.Jpn J Clin Oncol. 2006;36(6):344-50.
PubMed IF 2.5 혈액종양내과Abstract
BACKGROUND The association of epidermal growth factor receptor (EGFR) mutations with the response to conventional cytotoxic chemotherapeutic agents in non-small-cell lung cancer patients has not been investigated. We retrospectively analyzed the associations between response to chemotherapy and molecular markers associated with gefitinib responsiveness including EGFR mutations.
METHODS EGFR (exons 18, 19 and 21) and K-ras mutations (exon 2) were studied by direct sequencing and p-Erk and p-Akt expressions were studied by immunohistochemistry in archival paraffin embedded tissues. Response rate (RR) and time-to-progression (TTP) of prior chemotherapy by platinum, paclitaxel and gemcitabine were analyzed with respect to the presence of EGFR and K-ras mutations, and p-Erk and p-Akt expressions.
RESULTS Of 90 patients investigated, 75 received platinums and 45 received paclitaxel as first-line chemotherapy agents. The RRS and TTPS of platinum- and paclitaxel-containing regimens were not affected by EGFR or K-ras mutations, nor by p-Erk or p-Akt expression. Fifty-seven patients received gemcitabine as first- or second-line chemotherapy. RR was not affected by EGFR or K-ras mutations or by p-Akt expression. However, all responders to gemcitabine exhibited (+) p-Erk expression [RR 30.6% for p-Erk (+) versus 0% for p-Erk (-), P = 0.01]. TTP was not affected by EGFR or K-ras mutations or by p-Erk or p-Akt expression.
CONCLUSIONS EGFR mutations did not affect response to conventional chemotherapeutic agents, namely platinums, paclitaxel and gemcitabine. Our results also suggest that it may be undesirable to use gemcitabine in patients with tumors not expressing p-Erk.
- 282006
제1저자 윤원재 · 교신저자 류지곤
, , , , , ,
A comparison of covered and uncovered Wallstents for the management of distal malignant biliary obstruction.Gastrointest Endosc. 2006;63(7):996-1000.
PubMed IF 8 소화기내과Abstract
BACKGROUND The efficacy and complications of covered self-expandable metal stents (SEMS) remain controversial.
OBJECTIVE We conducted this study to compare the efficacies and complication rates of covered and uncovered SEMS in malignant biliary obstruction.
DESIGN Data on patients who underwent endoscopic retrograde biliary drainage with covered or uncovered Wallstents for the palliation of unresectable distal malignant biliary obstruction were collected. Stent patency, complications, and causes of stent occlusion were analyzed.
SETTING We collected the data retrospectively.
PATIENTS A total of 77 patients received Wallstents for unresectable distal malignant biliary obstruction.
INTERVENTIONS Endoscopic sphincterotomy was performed, and a Wallstent was deployed after guidewire passage. Polyurethane-covered Wallstents were used in 36 patients and uncovered Wallstents in 41 patients.
RESULTS Stent migration occurred in 3 of the covered Wallstent group and in 1 of the uncovered Wallstent group. Cholecystitis occurred in 1 of the covered Wallstent group but in none of the uncovered Wallstent group. Stent occlusion occurred after a mean of 398 days in the covered group and after 319 days in the uncovered Wallstent group (P > .05). Stent patency rates were 83%, 78%, 67%, and 54% at 100, 200, 300, and 400 days, respectively, in covered group and 83%, 66%, 54%, and 36% in the uncovered group, which was not significantly different.
LIMITATIONS This study is not a prospective randomized study and sample size is not large.
CONCLUSIONS Covered Wallstents are safe with acceptable complication rates. However, we found no significant difference between the stent patencies of covered and uncovered Wallstents.
- 272006
제1저자 윤호일 · 교신저자 임재준
, , , , , , , , ,
Lack of association between COPD and transforming growth factor-beta1 (TGFB1) genetic polymorphisms in Koreans.Int J Tuberc Lung Dis. 2006;10(5):504-9.
PubMed IF 3.6 호흡기내과Abstract
OBJECTIVE Many genetic variations have been suggested as genetic risk factors for the development of chronic obstructive pulmonary disease (COPD), including single nucleotide polymorphisms in the transforming growth factor-beta1 (TGFB1) gene. We attempted to elucidate the association between TGFB1 genetic polymorphisms and COPD among Koreans.
DESIGN The genotypes of 102 male patients with COPD and 159 volunteers with similar distributions of age, sex and smoking intensity, as well as normal pulmonary function, were determined for three previously associated TGFB1 single nucleotide polymorphisms (SNPs), -10807G/A (rs2241712) and -509T/C (rs1800469), located in or near the promoter, and 29T/C (rs1982073), located in exon 1 of the TGFB1 gene.
RESULTS No significant associations between COPD and the three TGFB1 SNPs could be identified. In addition, the haplotypes composed of three TGFB1 SNPs were not associated with the presence of COPD.
CONCLUSION These results differ from previous reports involving Caucasians, and might reflect racial differences in the pathogenesis of COPD.
- 262006
제1저자 김희정 · 교신저자 임재준
, , , , , , , ,
The prevalence of pulmonary parenchymal tuberculosis in patients with tuberculous pleuritis.Chest. 2006;129(5):1253-8.
PubMed IF 9.8 호흡기내과Abstract
STUDY OBJECTIVE To examine the prevalence and characteristics of parenchymal tuberculous pleuritis in adult patients.
DESIGN Prospective cohort study.
SETTING Three hospitals affiliated with Seoul National University in South Korea.
PATIENTS All patients > 15 years old with a diagnosis of tuberculous pleuritis were enrolled prospectively between January 1, 2004, and October 31, 2004.
INTERVENTIONS Diagnostic thoracocentesis and CT of the chest were done for each patient. Acid-fast bacilli (AFB) smears and cultures for Mycobacterium tuberculosis were requested if patients produced any sputum. A board-certified radiologist reviewed the chest radiographs for the presence and characteristics of any lesions.
MEASUREMENTS AND RESULTS One hundred six patients with tuberculous pleuritis were enrolled (median age, 53 years; range 16 to 89 years). Among them, 33 patients (31%) had sputum or bronchial washing findings positive for AFB smears or for M tuberculosis by culture. Lung parenchymal lesions were observed in 91 of the patients (86%) using chest CT; 39 patients (37%) with parenchymal lesions had radiographic characteristics of active pulmonary tuberculosis. In total, 62 patients (59%) had bacteriologically or radiographically active pulmonary tuberculosis. In addition, 78 patients (74%) had features of reactivated pulmonary tuberculosis.
CONCLUSIONS Lung parenchymal lesions were more common in this series of patients with tuberculous pleuritis than has been reported in previous studies. The patients mostly had radiographic features of reactivated, rather than primary, tuberculosis.
- 252006
제1저자 천재희 · 교신저자 정현채
, , , , , ,
Long-term outcomes after Helicobacter pylori eradication with second-line, bismuth-containing quadruple therapy in Korea.Eur J Gastroenterol Hepatol. 2006;18(5):515-9.
PubMed IF 2.1 소화기내과Abstract
OBJECTIVES To determine the long-term outcomes in terms of Helicobacter pylori and ulcer recurrence after second-line eradication with bismuth-containing quadruple regimens in Korea.
METHODS Sixty-seven patients with peptic ulcer disease after successful eradication using second-line quadruple therapies were prospectively followed up 1 month after treatment and then every 6 months or when dyspeptic symptoms reappeared to ascertain H. pylori and ulcer status.
RESULTS Three patients were lost during follow-up. The median duration of follow-up of the remaining 64 patients was 26.8 months. H. pylori recurrence occurred in 11 of these 64 patients (17.2%), giving a calculated reinfection rate of 6.0% per patient-year. Only one of the 11 patients was reinfected by 12 months after treatment completion. Four of 11 patients (36.4%) who became reinfected experienced peptic ulcer recurrence, but none of 53 patients who were not reinfected experienced recurrence. No evidence was obtained to indicate that the reinfection rate depended on the age, sex, ulcer location, or eradication regimens. The relapse of dyspeptic symptoms was the only factor predictive of H. pylori recurrence.
CONCLUSION This study suggests that the recurrence rate of H. pylori at 1 year after second-line, bismuth-containing quadruple therapy is low, but the annual reinfection rate is as high as 6%. Surveillance for H. pylori reinfection facilitating peptic ulcer recurrence may be warranted even after a second eradication, especially when dyspeptic symptoms reappear in Korea.
- 242006
제1저자 윤창환 · 교신저자 박영배
, , , , , , , , , ,
Intercellular adhesion molecule-1 is upregulated in ischemic muscle, which mediates trafficking of endothelial progenitor cells.Arterioscler Thromb Vasc Biol. 2006;26(5):1066-72.
PubMed IF 8.8 순환기내과Abstract
BACKGROUND Trafficking of transplanted endothelial progenitor cells (EPCs) to an ischemic organ is a critical step in neovascularization. This study was performed to elucidate the molecular mechanism of EPC trafficking in terms of adhesion molecules.
METHODS AND RESULTS Using murine hindlimb ischemia model, we examined expressions of E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in ischemic muscle by immunofluorescence. ICAM-1 was overexpressed in ischemic muscle compared with nonischemic muscle, whereas expressions of E-selectin, VCAM-1, and PECAM-1 did not show that much difference. ICAM-1 was also upregulated by hypoxia in murine endothelial cells (ECs) as assessed by immunoblot and flow cytometry. EPCs were attached to ECs specifically through ICAM-1/beta-2 integrin interaction in vitro. When EPCs were labeled with fluorescent dye or radioisotope (Tc-99m-HMPAO) and systemically administrated in vivo, EPCs preferentially homed to ischemic muscle. By blocking ICAM-1, EPCs entrapment to ischemic limb in vivo was significantly reduced and neovascularization induced by EPC transplantation was attenuated.
CONCLUSIONS ICAM-1 is upregulated by ischemia, and this is closely associated with EPCs entrapment to ischemic limb. Our findings suggest that ICAM-1 expression might be important in regulating the process of neovascularization through its ability to recruit EPCs.
- 232006
제1저자 이효석 · 교신저자 이효석
, , , , , , , , ,
A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg-positive chronic hepatitis B.Hepatology. 2006;43(5):982-8.
PubMed IF 18 소화기내과Abstract
Clevudine is a nucleoside analog with an unnatural beta-L configuration. In a phase I/II clinical trial, once daily doses ranging from 10 to 200 mg for 28 days were well tolerated, and produced significant antiviral activity. The present study was conducted to assess the degree and durability of the antiviral response to 12 weeks of clevudine treatment, and to investigate its safety and tolerability. A total of 98 patients with HBeAg-positive chronic hepatitis B were randomized to placebo (n=32), 30-mg clevudine (n=32), and 50-mg clevudine (n=34) groups. Patients were followed up after 12 weeks of treatment for a further 24 weeks off-therapy. Median serum hepatitis B virus DNA reductions from baseline at week 12 were 0.20, 4.49, and 4.45 log10 copies/mL in the placebo, 30-mg clevudine, and 50-mg clevudine groups, respectively (P < .0001). Posttreatment antiviral activities were sustained, with 3.32 and 2.99 log10 reductions at week 12 off-therapy and 2.28 and 1.40 log10 reductions at week 24 off-therapies in the 30- and 50-mg clevudine groups, respectively. Median serum alanine aminotransferase (ALT) levels decreased markedly from baseline during clevudine treatment and were maintained below the upper limit of normal throughout the 24 weeks off-therapy in the two clevudine-treated groups. The incidences of adverse events and treatment-emergent grade 3 or 4 laboratory abnormalities were similar for the three groups. In conclusion, clevudine showed potent antiviral activity during therapy and induced a sustained posttreatment antiviral effect for 6 months after a 12-week treatment period, and this was associated with a sustained normalization of ALT levels.
- 222006
제1저자 김강모 · 교신저자 윤정환
, , , , , ,
Bile acid-mediated induction of cyclooxygenase-2 and Mcl-1 in hepatic stellate cells.Biochem Biophys Res Commun. 2006;342(4):1108-13.
PubMed IF 2.5 소화기내과Abstract
In cholestatic liver diseases, bile acids induce hepatocyte apoptosis and thus cause liver injury, but hepatic stellate cells (HSCs) survive in the presence of bile acids. We attempted to analyze anti-apoptotic signaling pathways in HSCs against bile acid-induced apoptosis. In immortalized human HSCs and primarily cultured rat HSCs, bile acid treatment increased the expression levels of cyclooxygenase-2 (COX-2) and Mcl-1. COX-2 induction was found to be due to transcriptional enhancement dependent on p42/44, p38 MAPK, and JNK activation, whereas Mcl-1 induction resulted from bile acid-mediated protein stabilization in a Raf-1-dependent manner. Moreover, the inhibitions of either COX-2 activity by celecoxib or Mcl-1 induction by siRNA transfection rendered HSCs susceptible to bile acid-induced apoptosis. These results imply that the bile acid-mediated inductions of COX-2 and Mcl-1 may lead to HSC survival in cholestatic liver diseases.
- 212006
제1저자 김나영 · 교신저자 송인성
, , , , , , , ,
The effects of genetic polymorphisms of IL-1 and TNF-A on Helicobacter pylori-induced gastroduodenal diseases in Korea.Helicobacter. 2006;11(2):105-12.
PubMed IF 4.6 소화기내과Abstract
OBJECTIVE To evaluate whether or not genetic polymorphism of IL-1B, IL-1RN, and TNF-Alpha is an important factor in the different expression of gastroduodenal diseases after Helicobacter pylori infection.
METHODS This study consisted of 1360 subjects: control, gastric cancer (GC, intestinal type, and diffuse type), benign gastric ulcer (BGU), duodenal ulcer, and first-degree gastric cancer relative (GCR). IL-1Beta-511 and TNF-A-308 biallelic polymorphism were genotyped by 5' nuclease polymerase chain reaction (PCR) assays, and PCR-restriction fragment length polymorphism (PCR-RFLP). IL-1RN penta-allelic variable number of tandem repeats was genotyped by PCR.
RESULTS There was no difference in the genetic polymorphism of IL-1Beta-511, IL-1RN and TNF-A in the patients with gastric cancer regardless of H. pylori positivity compared with control. However, the frequencies of IL-1B-511 C/T (OR: 0.5, 95% CI: 0.3-0.7) and T carrier (OR: 0.6, 95% CI: 0.4-0.8) were lower in the H. pylori-positive BGU patients. The IL-1RN 2/2 was higher (OR: 5.5, 95% CI: 1.1-28.5) in the H. pylori-positive GCR. There was no significance in the polymorphism of TNF-Alpha-308 regardless of H. pylori-induced gastroduodenal diseases.
CONCLUSIONS The IL-1Beta-511 T-carrier polymorphism has a negative effect on the development of H. pylori-positive BGU, and high frequency of IL-1RN 2/2 was found in the H. pylori-positive relatives of GC patients, which suggest that this genetic polymorphism could play some role in the H. pylori-induced gastroduodenal diseases in Korea.
- 202006
제1저자 박흥우 · 교신저자 김윤근
, , , , , , , , , , , ,
Association between genetic variations of vascular endothelial growth factor receptor 2 and atopy in the Korean population.J Allergy Clin Immunol. 2006;117(4):774-9.
PubMed IF 11.2 알레르기내과Abstract
BACKGROUND Vascular endothelial growth factor (VEGF) has been suggested to be a key mediator in the development of atopy and T(H)2 inflammation.
OBJECTIVE We sought to evaluate the effects of variations in the gene coding VEGF receptor (VEGFR) 2 on intermediate phenotypes of asthma in the Korean population.
METHODS A cohort of 2055 children and adolescents responded to a questionnaire concerning asthma symptoms and risk factors and underwent methacholine bronchial challenge and skin tests. The VEGFR2 gene, including the promoter area, was sequenced on 24 healthy subjects to discover informative single nucleotide polymorphisms (SNPs; minor allele frequency >2%). After haplotype reconstruction, 4 tagging SNPs (IVS6+54A>G, +889G>A, +1416T>A, and IVS25-92G>A) were scored. These SNPs were also scored in 480 adult asthmatic patients to verify the above genetic association study.
RESULTS The prevalence of atopy was associated with a single SNP (+889G>A) of VEGFR2 with borderline significance (P = .048; relative risk, 1.13; 95% CI, 1.00-1.28). However, haplotype analysis showed that the atopy prevalence was strongly associated with a haplotype (AGAG) of VEGFR2 (P = .002; relative risk, 1.25; 95% CI, 1.09-1.42). As for airway hyperresponsiveness, neither individual SNPs nor haplotypes were found to be associated. Interestingly, the significant association was also found between atopy and the AGAG haplotype among adult asthmatic patients (P = .008; odds ratio, 1.66; 95% CI, 1.14-2.44).
CONCLUSIONS The present study demonstrated that genetic variations of VEGFR2 are significantly associated with atopy in the Korean population.
- 192006
제1저자 김철현 · 교신저자 유철규
, , , , , ,
FHIT protein enhances paclitaxel-induced apoptosis in lung cancer cells.Int J Cancer. 2006;118(7):1692-8.
PubMed IF 4.9 호흡기내과Abstract
The fragile histidine triad (FHIT) gene is a frequent target of deletions in lung cancer. Previous studies have shown that FHIT gene transfer into lung cancer cells lacking FHIT expression results in induction of apoptosis. However, the effect of FHIT expression on apoptosis induced by chemotherapeutic agents and its intracellular mechanism is poorly understood. This study was undertaken to elucidate the effect of FHIT expression and the role of Bcl-2-caspase signaling in paclitaxel-induced apoptosis in lung cancer cells. NCI-H358 lung cancer cells, which lack FHIT expression, were stably transfected with plasmid vector containing FLAG-tagged wildtype FHIT. We investigated effects of paclitaxel on apoptosis, activation of caspase system and expression of Bcl-2 family. We next evaluated whether these effects were reversed by blocking FHIT expression using siRNA. Paclitaxel enhanced apoptosis in FHIT-expressing cells compared to that in control vector-transfected cells, and this enhancement was suppressed by siRNA treatment. Activities of caspase-3 and caspase-7, but not of caspase-8, were higher in FHIT-expressing cells than in control vector-transfected cells, and this was reduced by siRNA treatment. When caspase activation was blocked by a pan-caspase inhibitor in FHIT-expressing cells, paclitaxel-induced apoptotic cell death was decreased similar to that in control vector-transfected cells. Bcl-2 and Bcl-xL expressions were down-regulated after paclitaxel treatment in FHIT-expressing cells, whereas Bax and Bad expressions were up-regulated. These were reversed by siRNA treatment. These results indicate that paclitaxel-induced apoptosis enhanced by FHIT expression in lung cancer cells might be associated with modulation of Bcl-2-caspase signaling.
- 182006
제1저자 박진식 · 교신저자 김효수
, , , , , , , ,
Common adrenergic receptor polymorphisms as novel risk factors for vasospastic angina.Am Heart J. 2006;151(4):864-9.
PubMed IF 3.4 순환기내과Abstract
BACKGROUND Sympathetic activity mediated by adrenergic receptors (ARs) appears to play an important role in controlling the vasomotor tone and, thus, may be associated with vasospastic angina (VA). We investigated the association of the common functional polymorphisms of the AR gene and VA. The candidates were alpha2CDel322-325, beta1Gly389Arg, beta2Arg16Gly, and beta2Gln27Glu polymorphisms.
METHODS Eighty-two patients with VA, confirmed by coronary angiography with or without ergonovine provocation test, and 114 apparently healthy control subjects were investigated for genotype of 4 AR polymorphisms and established risk factors of ischemic heart disease.
RESULTS The minor alleles were alpha2CDel322-325, beta1Gly389, beta2Gly16, and beta2Glu27 and their frequencies were 7%, 18%, 42%, and 29%, respectively, in the control subjects of this Korean population, which were different from those of other ethnic groups. On univariate analysis, age, smoking, male sex, alpha2CDel322-325 allele carrier state, and beta2Gln27 homozygote state were significant risk factors for VA. After multivariate analysis using multiple logistic regression model, age (odds ratio [OR] 1.809, CI 1.046-1.135, P < .0001), smoking (OR 4.902, CI 2.105-11.416, P = .0002), alpha2CDel322-325 allele carrier state (OR 5.132, CI 2.094-12.578, P = .0003), and beta2Gln27 allele homozygosity (OR 3.152, CI 1.364-7.285, P = .0072) remained as independent risk factors. In the combined genotype analysis, the effect of beta2Gln27 allele was evident only when the alpha2CDel322-325 allele was absent.
CONCLUSIONS The alpha2CDel322-325 allele carrier state and beta2Gln27 allele homozygote state were identified as novel risk factors of VA in this Korean population. This result suggests the importance of the adrenergic stimuli and the genetic background in the pathogenesis of the VA.
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