SCI 발표논문
전체 4,588편
- 1482007
제1저자 김상완 · 교신저자 김성연
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Acylated ghrelin secretion is acutely suppressed by oral glucose load or insulin-induced hypoglycemia independently of basal growth hormone secretion in humans.Horm Res. 2007;67(5):211-9.
PubMed IF 1.39 내분비대사내과Abstract
BACKGROUND Ghrelin has been reported to be the natural ligand of growth hormone (GH) secretagogue receptor, and it is known that exogenous ghrelin administration strongly stimulates GH release in humans. However, the effects of endogenous ghrelin on GH secretion and changes in ghrelin levels during dynamic changes in GH levels are not well understood.
METHODS Therefore, we measured circulating acylated ghrelin concentrations during oral glucose tolerance tests (OGTTs) in patients with active acromegaly (AA, n = 9) and in age/sex/BMI-matched group A controls (n = 12), and during insulin tolerance testing (ITT) in patients with GH deficiency (GHD, n = 10) and in group B controls (n = 10). Plasma acylated ghrelin, serum GH, insulin and glucose levels were measured during each test.
RESULTS Fasting plasma ghrelin levels correlated negatively with serum insulin levels in both group A and B controls (r = -0.665; p < 0.05) but not in patients with AA or GHD. During OGTTs, circulating ghrelin levels decreased significantly with a nadir at 30 min in both patients with AA (p < 0.05) and group A controls (p < 0.01). Also, ITTs were followed by a significant decrease in circulating ghrelin levels with a nadir at 30 min in patients with GHD (p < 0.05) and in group B controls (p < 0.05).
CONCLUSION The results of the study show that at baseline acylated ghrelin levels do not differ with respect to the GH status (GH excess or GH deficiency) and, furthermore, the suppression of acylated ghrelin levels during OGTT or ITT is independent of the GH response to the tests.
- 1472006
제1저자 강영애 · 교신저자 임재준
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Cost of treatment for multidrug-resistant tuberculosis in South Korea.Respirology. 2006;11(6):793-8.
PubMed IF 7.2 호흡기내과Abstract
OBJECTIVE AND BACKGROUND Costs associated with multidrug-resistant tuberculosis (MDR-TB) are higher than those associated with drug-susceptible TB because of the higher prices of second-line anti-TB drugs, the prolonged duration of treatment, greater productivity loss and higher mortality. The aim of this study was to estimate the cost of treatment for MDR-TB according to the treatment strategy and prognosis in South Korea.
METHODS We estimated the direct (medical and non-medical) and indirect cost for the treatment of MDR-TB according to the treatment strategies and prognosis: in medically treated, surgically treated and deceased patients groups. The same analyses were undertaken for drug-susceptible TB for comparison. The patients with MDR-TB or drug-susceptible TB were randomly selected from the TB cohort of Seoul National University Hospital, Seoul, South Korea.
RESULTS Direct costs per person were US$4000 (US$2527-4841) in the medically treated group, US$17,457 (US$10,133-26,418) in the surgically treated group and US$33,362 (US$25 386-40 338) in the deceased group. Total costs per person were US$15,856 (US$10,752-38,421), US$47,159 (US$20,587-77,622) and US$478,357 (US$257,377-777,778), respectively. For the patients with drug-susceptible TB, the total cost ranged from US$1680 to US$7637 (median US$2166).
CONCLUSIONS The cost for the treatment of MDR-TB is seven to 22 times that of managing the drug-susceptible TB in South Korea. Considering the high cost, transmissibility and considerable fatality of MDR-TB, there is a need to provide specific separate funding for multidrug-resistant tuberculosis.
- 1462006
제1저자 조영민 · 교신저자 박경수
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Plasma retinol-binding protein-4 concentrations are elevated in human subjects with impaired glucose tolerance and type 2 diabetes.Diabetes Care. 2006;29(11):2457-61.
PubMed IF 22.6 내분비대사내과Abstract
OBJECTIVE The dysregulation of adipokines is closely associated with the pathogenesis of insulin resistance and type 2 diabetes. Retinol-binding protein-4 (RBP4), a new adipokine, was recently reported to provide a link between obesity and insulin resistance. Here, we examined the relation between plasma RBP4 concentrations and various metabolic parameters in humans.
RESEARCH DESIGN AND METHODS An enzyme-linked immunosorbent assay was developed to measure human RBP4 plasma concentrations, which were then compared with various parameters related to insulin resistance in subjects with normal glucose tolerance (NGT; n = 57), impaired glucose tolerance (IGT; n = 48), and type 2 diabetes (n = 49).
RESULTS Plasma RBP4 concentrations were higher in the IGT and type 2 diabetic groups than in the NGT group (median 18.9 [range 11.2-45.8], 20.9 [9.9-48.5], and 18.1 microg/ml [9.3-30.5], respectively). However, no difference was found between plasma RBP4 concentrations in the IGT and type 2 diabetic groups. Plasma RBP4 concentrations were found to be associated with sex, waist circumference, fasting plasma glucose, and insulin resistance. Of these, sex and fasting plasma glucose levels were found to be independent determinants of plasma RBP4 concentration.
CONCLUSIONS Plasma RBP4 concentrations were found to be elevated in subjects with IGT or type 2 diabetes and to be related to various clinical parameters known to be associated with insulin resistance.
- 1452006
제1저자 박주경 · 교신저자 류지곤
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Gemcitabine chemotherapy versus 5-fluorouracil-based concurrent chemoradiotherapy in locally advanced unresectable pancreatic cancer.Pancreas. 2006;33(4):397-402.
PubMed IF 2.2 소화기내과Abstract
OBJECTIVES The aim of this study was to compare the survival benefits associated with gemcitabine chemotherapy and 5-fluorouracil (5-FU)-based concurrent chemoradiotherapy (CCRT) in locally advanced unresectable pancreatic cancer.
METHODS One hundred and thirty-eight locally advanced unresectable pancreatic cancer patients were retrospectively enrolled from January 1995 to January 2005. All cases were histologically proven, and patients received gemcitabine chemotherapy, 5-FU-based CCRT, or supportive care at Seoul National University Hospital.
RESULTS Median overall survival was 8.2 months. Twenty-six patients received gemcitabine chemotherapy, 56 patients 5-FU-based CCRT, and 56 patients supportive care. Weight loss and treatment modality were identified as independent prognostic factors by multivariate analysis. Patients in the 5-FU-based CCRT (overall survival, 10.4 months) and gemcitabine chemotherapy (11.3 months) groups showed survival benefit over those received supportive care (6.1 months, P < 0.0001). No grades 3 to 4 toxic adverse effects occurred in either treatment group and no statistical significant survival difference was found between gemcitabine chemotherapy and 5-FU-based CCRT (P = 0.5).
CONCLUSIONS Patients with locally advanced pancreatic cancer who received gemcitabine chemotherapy or 5-FU-based CCRT showed better survival than those who received supportive care only. Gemcitabine chemotherapy and 5-FU-based CCRT showed similar survival advantages.
- 1442006
제1저자 한세원 · 교신저자 김태유
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Clinical predictors versus epidermal growth factor receptor mutation in gefitinib-treated non-small-cell lung cancer patients.Lung Cancer. 2006;54(2):201-7.
PubMed IF 5.3 혈액종양내과Abstract
BACKGROUND Clinical predictors including Asian, female, adenocarcinoma and never-smoker and epidermal growth factor mutation are associated with gefitinib responsiveness in non-small-cell lung cancer. Direct comparison between clinical predictors and EGFR mutation for their predictive power has not been reported.
PATIENTS AND METHODS For 120 Korean NSCLC patients treated with gefitinib, we have analyzed EGFR mutational status in exons 18, 19 and 21. Patients were grouped according to the number of clinical predictors (female, adenocarcinoma and never-smoker). Response rate (RR), time-to-progression (TTP) and overall survival (OS) were analyzed. Multivariate analysis was performed to investigate which approach yielded better prediction.
RESULTS RRs according to number of clinical predictors were 0: 3.4%, 1: 17.1%, 2: 29.4% and 3: 33.3% (p=0.002). Patients with gefitinib-sensitive EGFR mutation showed 61.9% RR compared with 12.1% in the remaining patients (p<0.001). RRs were higher in patients with the EGFR mutations regardless of the number of clinical predictors. In multivariate analysis, gefitinib-sensitive EGFR mutation showed higher odds ratio of response (9.6, 95% confidence interval [CI] 3.2-28.7) compared with number of clinical predictors (1.7, 95% CI 1.1-2.7). Hazard ratio (HR) of TTP was also better in gefitinib-sensitive EGFR mutation (0.24, 95% CI 0.12-0.47) than number of clinical predictors (0.83, 95% CI 0.69-0.99). Only gefitinib-sensitive EGFR mutation was associated with improved OS (HR 0.25, 95% CI 0.12-0.52).
CONCLUSION EGFR mutation should be analyzed whenever possible for effective prediction of objective benefit from gefitinib in NSCLC patients with one or more clinical predictors.
- 1432006
제1저자 최형진 · 교신저자 박경수
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Polymorphisms in the ghrelin gene are associated with serum high-density lipoprotein cholesterol level and not with type 2 diabetes mellitus in Koreans.J Clin Endocrinol Metab. 2006;91(11):4657-63.
PubMed IF 5.4 내분비대사내과Abstract
CONTEXT Ghrelin is known to play a role in glucose metabolism and in beta-cell function. There are controversies regarding the role of ghrelin polymorphisms in diabetes and diabetes-related phenotypes.
OBJECTIVE The objective of this study was to examine polymorphisms of the ghrelin gene in a Korean cohort and investigate associations between them and susceptibility to type 2 diabetes and its related phenotypes.
DESIGN AND PATIENTS The ghrelin gene was sequenced to identify polymorphisms in 24 DNA samples. Common variants were then genotyped in 760 type 2 diabetic patients and 641 nondiabetic subjects. Genetic associations with diabetes-related phenotypes were also analyzed.
RESULTS Nine polymorphisms were identified, and four common polymorphisms [g.-1500C>G, g.-1062G > C, g.-994C > T, g.+408C > A (Leu72Met)] were genotyped in a larger study. The genotype distributions of these four common polymorphisms in type 2 diabetes patients were similar to those of normal nondiabetic controls. However, these four common polymorphisms were variably associated with several diabetes-related phenotypes, such as high-density lipoprotein (HDL) cholesterol, fasting plasma glucose, and homeostasis model assessment of insulin resistance. In particular, subjects harboring g.-1062C were associated with a lower serum HDL cholesterol level after adjusting for other variables (P = 0.0004 or 0.01 after Bonferroni correction for 24 tests).
CONCLUSION The aforementioned four common polymorphisms in the ghrelin gene were not found to be significantly associated with susceptibility to type 2 diabetes mellitus in the Korean population. However, the common polymorphism g.-1062G > C in the promoter region of the ghrelin gene was found to be significantly associated with serum HDL cholesterol levels.
- 1422006
제1저자 이상민 · 교신저자 유철규
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Hypoxia confers protection against apoptosis via PI3K/Akt and ERK pathways in lung cancer cells.Cancer Lett. 2006;242(2):231-8.
PubMed IF 11.8 호흡기내과Abstract
Hypoxia confers protection against apoptosis in cancer cells, and this hypoxia-induced resistance to apoptosis has been suggested to be associated with genetic and adaptive changes. However, it is not clear whether survival signals, such as the PI3K/Akt and ERK pathways are involved. We investigated the roles of these pathways in hypoxia-induced protection against apoptosis in lung cancer cells. Treatment of cells with either ultraviolet (UV) or etoposide induced apoptosis time-dependently in A549 and NCI-H157 cells. However, though hypoxia alone neither induced apoptosis nor reduced cell survival, it suppressed the apoptosis induced by UV or etoposide. Moreover, hypoxia activated the PI3K/Akt and ERK pathways, and blocking the activation of either pathway reversed resistance to UV- and etoposide-induced apoptosis in response to hypoxia. These results suggest that hypoxia confers resistance to UV- or etoposide-mediated apoptosis in lung cancer cells via the activations of the PI3K/Akt and the ERK pathways.
- 1412006
제1저자 한주용 · 교신저자 김효수
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Beta-catenin overexpression reduces myocardial infarct size through differential effects on cardiomyocytes and cardiac fibroblasts.J Biol Chem. 2006;281(41):30979-89.
PubMed IF 4.1 순환기내과Abstract
Beta-catenin is a transcriptional regulator of several genes involved in survival and proliferation. Although previous studies suggest that beta-catenin may be involved in the process of preconditioning and healing after myocardial infarction (MI), little is known regarding the role of beta-catenin in cardiomyocytes and cardiac fibroblasts. We investigated the role of beta-catenin in cardiomyocytes and cardiac fibroblasts and whether beta-catenin overexpression could reduce MI size. Adenovirus-mediated gene transfer of nonphosphorylatable constitutively active beta-catenin (Ad-catenin) decreased apoptosis in cardiomyocytes and cardiac fibroblasts with increased expression of survivin and Bcl-2. Although Ad-catenin increased the percentage of cells in the S phase with enhanced expression of cyclin D1 and E2 in both cell types, the increase in cell number was only evident in cardiac fibroblasts, whereas hypertrophy and binuclear cells were more prominent in cardiomyocytes. All of these effects of beta-catenin gene transfer were blocked by inhibition of its nuclear translocation. Furthermore, Ad-catenin enhanced the expression of vascular endothelial growth factor in both cells and induced differentiation of cardiac fibroblasts into myofibroblasts. In a rat MI model, injection of Ad-catenin into the infarct border zone resulted in a significantly decreased MI size with anti-apoptotic effect and cell cycle activation in both cardiomyocytes and myofibroblasts. beta-Catenin may play an important role in the healing process after MI by promoting survival and cell cycle not only in cardiomyocytes but also in cardiac fibroblasts with its differentiation into myofibroblasts.
- 1402006
제1저자 조영민 · 교신저자 조영민
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Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells.Biochem Biophys Res Commun. 2006;348(4):1472-8.
PubMed IF 2.5 내분비대사내과Abstract
Embryonic cells before implantation are exposed to a hypoxic condition and dependent on anaerobic metabolism. Human embryonic stem cells (HESCs) derived from pre-implantation blastocyst also grow well in hypoxic conditions. Expecting that the differentiating HESCs might mimic anaerobic-to-aerobic metabolic transition of the early human life, we examined the mitochondria-related changes in these cells. We observed that mitochondrial mass and mitochondrial DNA content were increased with differentiation, which was accompanied by the increase of the amount of ATP (4-fold) and its by-product reactive oxygen species (2.5-fold). The expression of various antioxidant enzymes including mitochondrial and cytoplasmic superoxide dismutases, catalase, and peroxiredoxins showed a dramatic change during the early differentiation. In conclusion, HESC differentiation was followed by dynamic changes in mitochondrial mass, ATP and ROS production, and antioxidant enzyme expressions. Therefore, the HESCs would serve as a good model to examine the mitochondrial biology during the early human differentiation.
- 1392006
제1저자 김성한 · 교신저자 지영미
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Cell-mediated immune responses to smallpox vaccination.Clin Vaccine Immunol. 2006;13(10):1172-4.
PubMed IF 2.06 감염내과Abstract
We report that vaccine dilution (1:1 or 1:10) and previous vaccinia virus vaccination status had no significant effect on cell-mediated immune responses (i.e., the immediate vaccinia virus-specific gamma interferon-producing T-cell response measured by enzyme-linked immunospot assay) 1 month after smallpox vaccination (Lancy-Vaxina; Berna Biotech, Switzerland).
- 1382006
제1저자 천재희 · 교신저자 정현채
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Combinations containing amoxicillin-clavulanate and tetracycline are inappropriate for Helicobacter pylori eradication despite high in vitro susceptibility.J Gastroenterol Hepatol. 2006;21(10):1590-5.
PubMed IF 3.5 소화기내과Abstract
BACKGROUND The purpose of the present paper was to evaluate the efficacy and tolerability of amoxicillin-clavulanate and tetracycline-based quadruple therapy as an alternative second-line treatment for H. pylori infection.
METHODS The study subjects consisted of 54 patients infected with H. pylori, in whom initial triple therapy had failed. Subjects were randomized to receive the following 7-day therapies: (i) pantoprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., amoxicillin-clavulanate 1000 mg b.i.d., and tetracycline 500 mg q.i.d. (PBAT); or (ii) pantoprazole 40 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. (PBMT). Eradication rates based on antibiotic susceptibility, drug compliance and side-effect rates were evaluated and compared.
RESULTS The H. pylori eradication rates were 16.0%/17.4% with PBAT and 65.5%/70.4% with PBMT by intention-to-treat (P<0.001) and per-protocol analyses (P<0.001), respectively. In patients who received PBAT, the eradication rates were only 16.7% (2/12) for both amoxicillin and tetracycline-susceptible H. pylori strains. Drug compliance and side-effect rates were similar in the two groups.
CONCLUSIONS Despite high individual in vitro antimicrobial activity, amoxicillin-clavulanate and tetracycline-based quadruple therapy showed low eradication rates, which strongly suggests that it should not be considered as a therapeutic option for H. pylori eradication.
- 1372006
제1저자 이윤종 · 교신저자 송영욱
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Interleukin-18 promoter polymorphisms in patients with Behçet's disease.Hum Immunol. 2006;67(10):812-8.
PubMed IF 2.1 류마티스내과Abstract
Behçet's disease (BD) is an idiopathic systemic inflammatory disease and is considered to be a T helper 1 (Th1) type cytokine driven disorder. Moreover, levels of interleukin-18 (IL-18), a pivotal mediator of Th1 cytokine response, have been reported to be upregulated in BD. Therefore, we investigated the distribution of IL-18 promoter -607 C/A and -137 G/C polymorphisms in 103 BD patients (mean age 41.0 years; 48 male, 55 female) using allele-specific-polymerase chain reaction. As compared with healthy control subjects, BD patients had a significantly higher frequency of the -607 CC genotype (42.7% vs 23.3%, odds ratio [OR] = 2.455, 95% confidence interval [CI] = 1.350-4.461, p(c) = 0.021) and a higher frequency of the -607 C allele (60.7% vs 48.1%, OR = 1.668, 95% CI = 1.129-2.464, p = 0.0101). Haplotype analysis showed that BD patients had significantly less -607A/-137G haplotype (27.3% vs 44.2%, OR = 0.469, 95% CI = 0.268-0.820, p(c) = 0.032) and -607A/-137G haplotype homozygote (5.8% vs 20.4%, OR = 0.242, 95% CI = 0.096-0.612, p(c) = 0.014) than control subjects. In addition, the frequency of -607C/-137G haplotype homozygote was significantly higher in BD patients than control subjects (48.5% vs 20.4%, OR = 3.684, 95% CI = 1.997-6.791, p(c) = 0.0014). Although there were no associations between the polymorphisms and clinical manifestations or severity, patients with the -607 CC genotype or -607C/-137G haplotype homozygote showed significantly earlier symptom development (p = 0.034 by ANOVA; p = 0.009 by t-test, respectively) than those with other genotypes or diplotypes. These results suggest that the IL-18 promoter gene is a candidate susceptibility gene in BD patients.
- 1362006
제1저자 진호준 · 교신저자 채동완
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The clinical significances of simple renal cyst: Is it related to hypertension or renal dysfunction?Kidney Int. 2006;70(8):1468-73.
PubMed IF 21.8 신장내과Abstract
Simple renal cyst has controversy related to hypertension and renal dysfunction. We analyzed the impacts of cyst on hypertension and renal dysfunction, focusing on elimination of the confounding factors. We grouped 436 patients and 436 controls by characteristics of cyst and stratified with clinical parameters among 6603 patients who had routine health check-up in Seoul National University Bundang Hospital, Seongnam, Korea. The presence of cyst was related to hypertension but not to renal dysfunction. The number and the size of cyst were independent risk factors to the prevalence of hypertension. The presence of multiple renal cysts was related to hypertension in males, in persons over the age of 60 years, in persons with glomerular filtration rate (GFR) more than 60 ml/min/1.73 m2, or in persons without proteinuria. The effect of the large cyst and the peripheral cyst on the prevalence of hypertension was similar to that of the multiple cyst. The blood pressure of the multiple-cyst group, the large-cyst group, or the peripheral-cyst group was higher than that of the single-cyst group, the small-cyst group, or the perihilar-cyst group, respectively, regardless of antihypertensive medications. In conclusion, the presence of cysts or characteristics of cyst were not related to the decreased GFR. In conclusion, the presence of simple renal cyst was related to hypertension but not to renal dysfunction. The effect of simple cyst on hypertension was evident in males, aged persons, and persons without the evidence of renal disease. The number, size, and location were important characteristics of cyst related to hypertension.
- 1352006
제1저자 정성수 · 교신저자 박경수
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Sp1 mediates repression of the resistin gene by PPARgamma agonists in 3T3-L1 adipocytes.Biochem Biophys Res Commun. 2006;348(1):253-8.
PubMed IF 2.5 내분비대사내과Abstract
Resistin is an adipokine related to obesity and insulin resistance. Expression of the resistin gene is repressed by the treatment of peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, thiazolidinediones (TZDs). In this study, we investigated the mechanism by which TZDs inhibit the resistin gene expression. Resistin gene expression was decreased by TZD in fully differentiated 3T3-L1 adipocytes, which was abolished after treatment of cycloheximide (a protein synthesis inhibitor). TZD could not repress the expression of the resistin gene in the presence of mithramycin A (an Sp1 binding inhibitor). Sp1 binding site of the resistin promoter (-122/-114bp) was necessary for the repression. Further investigation of the effect of TZDs on the modification of Sp1 showed that the level of O-glycosylation of Sp1 was decreased in this process. These results suggest that PPARgamma activation represses the expression of the resistin gene by modulating Sp1 activity.
- 1342006
제1저자 조상호,연태진 · 교신저자 김효수
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Renal toxicity evaluation and comparison between visipaque (iodixanol) and hexabrix (ioxaglate) in patients with renal insufficiency undergoing coronary angiography: the RECOVER study: a randomized controlled trial.J Am Coll Cardiol. 2006;48(5):924-30.
PubMed IF 22.3 순환기내과Abstract
OBJECTIVES This study sought to compare the nephrotoxicity of iodixanol and ioxaglate in patients with renal impairment undergoing coronary angiography.
BACKGROUND Iodixanol, a nonionic, dimeric, iso-osmolar contrast medium (IOCM), may be less nephrotoxic than low-osmolar contrast media (LOCM) in high-risk patients.
METHODS In a prospective, randomized trial in 300 adults with creatinine clearance (CrCl) < or =60 ml/min, patients received either iodixanol or ioxaglate and underwent coronary angiography with or without percutaneous coronary intervention. The primary end point was the incidence of contrast-induced nephropathy (CIN) (an increase in serum creatinine [SCr] > or =25% or > or =0.5 mg/dl [> or =44.2 mumol/l]). The incidence of CIN in patients with severe renal impairment at baseline (CrCl <30 ml/min) or diabetes and in those receiving large doses (> or =140 ml) of contrast medium was also determined.
RESULTS The incidence of CIN was significantly lower with iodixanol (7.9%) than with ioxaglate (17.0%; p = 0.021), corresponding to an odds ratio (OR) of CIN of 0.415 (95% confidence interval [CI] 0.194 to 0.889) for iodixanol. The incidence of CIN was also significantly lower with iodixanol in patients with severe renal impairment (p = 0.023) or concomitant diabetes (p = 0.041), or in patients given > or =140 ml of contrast media (p = 0.038). Multivariate analysis identified use of ioxaglate (OR 2.65, 95% CI 1.11 to 6.33, p = 0.028), baseline SCr, mg/dl (OR 2.0, 95% CI 1.04 to 3.85, p = 0.038), and left ventricular ejection fraction, % (OR 0.97, 95% CI 0.94 to 0.99, p = 0.019) as independent risk factors for CIN.
CONCLUSIONS The IOCM iodixanol was significantly less nephrotoxic than ioxaglate, an ionic, dimeric LOCM. (The RECOVER Trial; http://clinicaltrials.gov; NCT00247325).
- 1332006
제1저자 김진 · 교신저자 정숙향
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Elevated plasma osteopontin levels in patients with hepatocellular carcinoma.Am J Gastroenterol. 2006;101(9):2051-9.
PubMed IF 7.6 소화기내과Abstract
OBJECTIVES Osteopontin (OPN) is a secreted glycoprotein, frequently associated with various tumors. We investigated the usefulness of plasma OPN level as a biomarker for hepatocellular carcinoma (HCC).
METHODS We determined plasma levels of OPN, alpha-fetoprotein (AFP), and prothrombin induced by vitamin K absence II (PIVKA II) in a group of 62 HCC patients, in 60 patients with chronic liver diseases, and in 60 healthy control individuals using a standardized ELISA kit. To determine the source of elevated plasma level of OPN, immunohistochemical analysis of 285 HCC samples on tissue microarray was performed.
RESULTS Plasma OPN levels in the HCC patients (median 954 ng/mL, range 168-5,742) were significantly higher (p-value < 0.001) than those patients with chronic liver diseases (381 ng/mL, 29-1,688) or of a healthy control group (155 ng/mL, 10-766). Within the HCC patient group, plasma OPN level increased significantly with advancing degree of Child-Pugh class and of tumor stage. Diagnostic sensitivity and specificity of OPN for HCC was 87% and 82%, respectively (cut-off value: 617.6 ng/mL). OPN had a greater area under curve value (0.898) than AFP (0.745) or PIVKA II (0.578), suggesting superior diagnostic accuracy of OPN. Immunohistochemistry of 285 samples of HCC showed that OPN was expressed in 92 of 285 tumors (32.3%). OPN expression was found in the malignant hepatocytes and cancer-infiltrating macrophages, not in the noncancerous hepatocytes or Kupffer cells.
CONCLUSIONS These data propose elevated plasma OPN levels as a potential biomarker for HCC.
- 1322006
제1저자 김덕겸 · 교신저자 임재준
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Microarray analysis of gene expression associated with extrapulmonary dissemination of tuberculosis.Respirology. 2006;11(5):557-65.
PubMed IF 7.2 호흡기내과Abstract
OBJECTIVE Although extrapulmonary organs are involved in 20% of patients with tuberculosis, the host genetic factors associated with the extrapulmonary dissemination of tuberculosis are not yet known. The aim of this study was to identify the host genetic factors associated with the extrapulmonary dissemination of tuberculosis by comparing gene expression profiles of patients who had recovered from extrapulmonary tuberculosis and those who had recovered from pulmonary tuberculosis.
METHODS Five patients from each group were enrolled. Total RNA was extracted from peripheral blood mononuclear cells that had been incubated for 48 h with whole lysate of Mycobacterium tuberculosis (H37Rv, 0.5 microg/mL). Gene expression profiles were acquired using the GeneChip array and its applied systems. Gene expression profiles from five patients with previous extrapulmonary tuberculosis and one pooled control sample from five patients with previous pulmonary tuberculosis were analysed and compared. Genes that were expressed concordantly in more than 80% of arrays and that showed more than twofold changes in at least one array among samples from patients who had recovered from extrapulmonary tuberculosis were identified.
RESULTS Compared with the control sample, the expression of 16 genes, including those for tumour necrosis factor (TNF)-alpha and cathepsin W, was increased, and the expression of 45 genes including that for TNF-receptor superfamily member 7 (TNFRSF7), was decreased in the extrapulmonary tuberculosis patients. The altered expression of the TNF-alpha, cathepsin W and TNFRSF7 genes was confirmed by quantitative RT-PCR.
CONCLUSIONS Altered expression of the genes for TNF-alpha, cathepsin W and TNFRSF7 may be risk factors for the extrapulmonary dissemination of tuberculosis in humans.
- 1312006
제1저자 예병덕 · 교신저자 정현채
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Omeprazole may be superior to famotidine in the management of iatrogenic ulcer after endoscopic mucosal resection: a prospective randomized controlled trial.Aliment Pharmacol Ther. 2006;24(5):837-43.
PubMed IF 6.8 소화기내과Abstract
BACKGROUND Acid suppressing agents are widely used to treat the iatrogenic ulcers following endoscopic mucosal resection for gastric neoplasms. However, the relative merits of proton pump inhibitor or histamine(2)-receptor antagonist for endoscopic mucosal resection-induced ulcers are not known.
AIM To prospectively compare omeprazole and famotidine for the healing of endoscopic mucosal resection-induced ulcers and for bleeding control.
METHODS After endoscopic mucosal resection, patients were randomly assigned to omeprazole (20 mg/day) or to famotidine (40 mg/day) group for a 28-day treatment period. The ulcer sizes and stages, bleeding rates and ulcer-related symptoms were compared.
RESULTS A total of 100 patients were randomized equally to each group. Forty-one patients in each group were finally compared. The two groups were comparable in terms of baseline characteristics. Twenty-eight days after treatment, the two groups were not different with respect to ulcer stage (P = 0.137) or ulcer reduction ratio (P = 0.380). No difference was observed with respect to ulcer-related symptoms (P = 0.437) and no bleeding episode occurred in any of the 82 patients. In subgroup that underwent endoscopic submucosal dissection, fewer patients in the omeprazole group showed active ulcers than those in the famotidine group (P = 0.035).
CONCLUSION Our results demonstrate that omeprazole may be superior to famotidine for iatrogenic ulcers following endoscopic mucosal resection, especially for large ulcers.
- 1302006
제1저자 김현지 · 교신저자 임재준
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Prognostic factors for surgical resection in patients with multidrug-resistant tuberculosis.Eur Respir J. 2006;28(3):576-80.
PubMed IF 23.8 호흡기내과Abstract
Although surgical lung resection could improve prognosis in some patients with multidrug-resistant tuberculosis (MDR-TB), there are no reports on the optimal candidates for this surgery. The aim of the present study was to elucidate the prognostic factors for surgery in patients with MDR-TB. Patients who underwent lung resection for the treatment of MDR-TB between March 1993 and December 2004 were included in the present study. Treatment failure was defined as greater than or equal to two of the five cultures recorded in the final 12 months of treatment being positive, any one of the final three cultures being positive, or the patient having died during treatment. The variables that affected treatment outcomes were identified through univariate and multivariate logistic regression analysis. In total, 79 patients with MDR-TB were included in the present study. The treatment outcomes of 22 (27.8%) patients were classified as failure. A body mass index <18.5 kg x m(-2), primary resistance, resistance to ofloxacin and the presence of a cavitary lesion beyond the range of the surgical resection were associated with treatment failure. Low body mass index, primary resistance, resistance to ofloxacin and cavitary lesions beyond the range of resection are possible poor prognostic factors for surgical lung resection in multidrug-resistant tuberculosis patients.
- 1292006
제1저자 김나영 · 교신저자 정현채
, , , , , , ,
Institutional difference of antibiotic resistance of Helicobacter pylori strains in Korea.J Clin Gastroenterol. 2006;40(8):683-7.
PubMed IF 2.7 소화기내과Abstract
GOALS This study was performed to evaluate whether the prevalence rates of primary antibiotic resistance in Helicobacter pylori isolates could be different between 2 institutions, which are located in the different areas in Korea, and to evaluate the effect of antibiotic resistance on the eradication rate of H. pylori.
STUDY H. pylori were isolated from gastric mucosal biopsy specimens obtained from 113 Koreans, who did not have any eradication history. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and moxifloxacin were examined according to the agar dilution method by 1 technician.
RESULTS All of these patients were treated with the same regimen, proton pump inhibitor-amoxicillin-clarithromycin triple therapy. There was a statistical difference in resistance to metronidazole, levofloxacin, and moxifloxacin among 6 antibiotics between 2 institutions located in Seoul and Gyeonggi province. The rates of eradication were 94.2% for the clarithromycin and amoxicillin-susceptible strains, and 42.8% for the amoxicillin-susceptible and clarithromycin-resistant strains. In contrast, eradication rate was 100% for the amoxicillin-resistant strains.
CONCLUSIONS These results show that there is institutional difference of antibiotic resistance of H. pylori, explaining the institutional difference of eradication rate of H. pylori. The resistance to clarithromycin seems to be an important determinant for the eradication by proton pump inhibitor triple therapy but resistance to amoxicillin does not have any effect.
- 1282006
제1저자 임재준 · 교신저자 Steven M Holland
, , ,
Evolution of an intronic microsatellite polymorphism in Toll-like receptor 2 among primates.Immunogenetics. 2006;58(9):740-5.
PubMed IF 2.1 호흡기내과Abstract
Nonhuman primates express varying responses to Mycobacterium tuberculosis: New World monkeys appear to be resistant to tuberculosis (TB) while Old World monkeys seem to be particularly susceptible. The aim of this study was to elucidate the presence of the regulatory guanine-thymine (GT) repeat polymorphisms in intron 2 of Toll-like receptor 2 (TLR2) associated with the development of TB in humans and to determine any variations in these microsatellite polymorphisms in primates. We sequenced the region encompassing the regulatory GT repeat microsatellites in intron 2 of TLR2 in 12 different nonhuman primates using polymerase chain reaction amplification, TA cloning, and automatic sequencing. The nonhuman primates included for this study were as follows: chimpanzee (Pan troglodytes), bonobo (Pan paniscus), gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus), Celebes ape (Macaca nigra), rhesus monkey (Macaca mulatta), pigtail macaque (Macaca nemestrina), patas monkey (Erythrocebus patas), spider monkey (Ateles geoffroyi), Woolly monkey (Lagothrix lagotricha), tamarin (Saguinus labiatus), and ring-tailed lemur (Lemur catta). Nucleotide sequences encompassing the regulatory GT repeat region are similar across species and are completely conserved in great apes. However, Old World monkeys lack GT repeats altogether, while New World monkeys and ring-tailed lemurs have much more complex structures around the position of the repeats. In conclusion, the genetic structures encompassing the regulatory GT repeats in intron 2 of human TLR2 are similar among nonhuman primates. The sequence is most conserved in New World monkeys and less in Old World monkeys.
- 1272006
제1저자 오세일 · 교신저자 최윤식
, , ,
Atypical atrioventricular nodal reentrant tachycardia in a patient with fasciculoventricular pathway.Heart Rhythm. 2006;3(9):1085-7.
- 1262006
제1저자 권동아 · 교신저자 손대원
, , , , , , , , ,
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.
- 1252006
제1저자 김성한 · 교신저자 오명돈
, , , , , , , , ,
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.
- 1242006
제1저자 김강모 · 교신저자 윤정환
, , , , , , ,
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.
- 1232006
제1저자 김태유 · 교신저자 K. Robertson
, , , ,
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.
- 1222006
제1저자 장혜련 · 교신저자 한진석
, , , , , , , ,
From bench to bedside: diagnosis of Gitelman's syndrome -- defect of sodium-chloride cotransporter in renal tissue.Kidney Int. 2006;70(4):813-7.
- 1212006
제1저자 김윤준 · 교신저자 이효석
, , , , , ,
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.
- 1202006
제1저자 조현재 · 교신저자 김효수
, , , , , , , , , ,
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.
- 1192006
제1저자 이경훈 · 교신저자 허대석
, , , , , , , , ,
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.
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