SCI 발표논문
전체 4,588편
- 1782007
제1저자 구보경 · 교신저자 박경수
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Polymorphisms of KCNJ11 (Kir6.2 gene) are associated with Type 2 diabetes and hypertension in the Korean population.Diabet Med. 2007;24(2):178-86.
PubMed IF 3.3 내분비대사내과Abstract
AIMS Kir6.2 is found in the pancreatic B-cell, cardiac and skeletal muscle and non-vascular smooth muscle. KCNJ11, encoding Kir6.2, has been shown to be associated with both Type 2 diabetes mellitus and cardiovascular disease in several populations. In this study, we investigated whether polymorphisms in KCNJ11 are associated with Type 2 diabetes and other metabolic phenotypes in the Korean population.
METHODS We sequenced KCNJ11 to identify common polymorphisms using 24 Korean DNA samples. Of the 14 polymorphisms found in KCNJ11, six common ones [genomic sequence (g.)-1709A>T, g.-1525T>C, g.67G>A (E23K), g.570C>T (A190A), g.1009A>G (I337V), and g.1388C>T] were genotyped in 761 Type 2 diabetic patients and in 630 non-diabetic subjects.
RESULTS All the polymorphic loci in KCNJ11 are in strong linkage disequilibrium in the Korean population and act as one haplotype block. g.67G>A and g.1009A>G were associated with an increased risk of Type 2 diabetes [age, sex, and body mass index (BMI)-adjusted odds ratios (OR) = 1.376 (1.085-1.745), P = 0.008 and 1.411 (1.111-1.791), P = 0.005, respectively], as was one haplotype (A-T-A-C-G-C in the order of polymorphisms as shown above) containing g.67A and g.1009G [OR = 1.359 (1.080-1.709), P = 0.009]. The haplotype (A-T-A-C-G-C) was also strongly associated with hypertension [OR = 1.655 (1.288-2.126), P < 0.001].
CONCLUSIONS Polymorphisms in KCNJ11 are associated with Type 2 diabetes and also with hypertension in the Korean population.
- 1772007
제1저자 임수 · 교신저자 장학철
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Visceral fatness and insulin sensitivity in women with a previous history of gestational diabetes mellitus.Diabetes Care. 2007;30(2):348-53.
PubMed IF 22.6 내분비대사내과Abstract
OBJECTIVE The purpose of this study was to investigate the insulin sensitivity and visceral fatness in women with previous gestational diabetes mellitus (GDM), who are prone to develop type 2 diabetes.
RESEARCH DESIGN AND METHODS A 75-g oral glucose tolerance test (OGTT) performed 1 year postpartum identified 21 GAD(-) women with previous GDM and impaired glucose tolerance (GDM-IGT). Sixty age- and BMI-matched women with normal glucose tolerance (GDM-NGT) were selected by 1:3 matching to the GDM-IGT group. Another 18 women with normal glucose metabolism during a previous pregnancy and no family history of diabetes were recruited as the normal control group. Age and BMI matching was performed using a range of +/-1.0 years and +/-1.0 kg/m(2), respectively. Total body fat was measured by tetrapolar bioelectrical impedance, and visceral fat was determined using a single cut of a computed tomography scan. Insulin sensitivity was determined by the minimal model technique using the frequently sampled intravenous glucose tolerance test.
RESULTS One year postpartum, visceral fat was greater in the GDM-IGT group than in the age- and BMI-matched GDM-NGT or normal control groups. The insulin sensitivity index was lower in the GDM-IGT group than in the GDM-NGT or normal control groups. beta-Cell function, as measured by the acute insulin response to glucose, was also lower in GDM-IGT.
CONCLUSIONS High body fat content, especially visceral fat content, and a low insulin response to glucose seem to contribute simultaneously to the development of impaired glucose metabolism in Korean women with previous GDM.
- 1762007
제1저자 박흥우 · 교신저자 조상헌
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Outcomes in occupational asthma caused by reactive dye after long-term avoidance.Clin Exp Allergy. 2007;37(2):225-30.
PubMed IF 5 알레르기내과Abstract
BACKGROUND Reactive dye (RD) is known to be a causative agent of occupational asthma (OA). However, to date, no report has been issued concerning the long-term outcomes of RD-induced OA.
OBJECTIVES We sought to evaluate the long-term outcomes in cases of OA caused by RD.
METHODS A total of 11 OA patients confirmed by RD bronchial challenge were enrolled in this study. First and second follow-up examinations were conducted at 4.3+/-2.3 and 13.7+/-2.3 years (means+/-SD) after the initial examinations, respectively. Skin prick test with RD and 11 common inhalant allergens, pulmonary function test, methacholine bronchial provocation testing, symptom and medication scores were determined at each visit. In addition, inflammatory cells in induced sputum were measured at the second follow-up examinations.
RESULTS Reduced lung function at initial examinations did not recover at the first and second examinations despite cessation of exposure and proper pharmacological treatment. In addition, asthma severity (as determined by symptom and medication scores) and non-specific airway hyper-responsiveness to methacholine also did not improve. However, skin reactivity to RD almost disappeared at the second examinations. Interestingly, four of the six patients who showed negative skin responses to all 11 common inhalant allergens at initial examinations were found to be atopic at the second examinations. Moreover, in terms of airway inflammation, seven of the 11 patients showed eosinophilia in induced sputum (> or =3%) at the second examinations despite having been on high-dose inhaled corticosteroid medication.
CONCLUSION The present study demonstrates that reduced lung function and asthmatic symptoms persist in RD-induced OA even after long-term exposure avoidance.
- 1752007
제1저자 임춘수 · 교신저자 임춘수
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Association between the clara cell secretory protein (CC16) G38A polymorphism and the progression of IgA nephropathy.Clin Nephrol. 2007;67(2):73-80.
PubMed IF 0.8 신장내과Abstract
AIMS Clara cell secretory protein (CC16) is a protein with anti-inflammatory and immunomodulatory properties. Moreover, both CC16 gene knockout and antisense-transgenic mouse models developed glomerulonephritis resembling IgA nephropathy (IgAN). In the present study, we evaluated the influence of the G38A polymorphism in the CC16 gene exon 1 on the development and progression of IgAN.
METHODS Korean patients with biopsy-proven IgAN (n=267) with a minimal follow-up of 4 years (mean +/- SD 103.8 +/- 52.6 months) were recruited. Healthy normal subjects (n=315) were included as controls. The G38A polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism method.
RESULTS GG, GA and AA genotype frequencies were 36.3, 50.2 and 13.5% in IgAN patients, respectively, and 34.3, 50.2 and 15.5% in controls (chi2 = 0.596, p = 0.742). The G allele frequency was 0.614 in IgAN patients and 0.594 in controls (chi2 = 0.429, p = 0.512). Moreover, the GG genotype frequencies were 40.4% in patients showing stable disease course and 26.6% in those with progressive disease (chi2 = 4.029, p = 0.045). Patients with the GG genotype showed a better outcome by Kaplan-Meier analysis in terms of renal survival (p = 0.043). The CC16 polymorphism remained an independent risk factor for progression after multivariate analysis (Cox regression model, HR for CC16 AA genotype: 2.34, 95% CI 1.19-4.64, p = 0.014).
CONCLUSION Our results suggest that CC 16 gene G38A polymorphism is not associated with the development of IgAN, but that it is an important marker of progression in IgAN.
- 1742007
제1저자 이은봉 · 교신저자 송영욱
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Haplotype association of IL-8 gene with Behcet's disease.Tissue Antigens. 2007;69(2):128-32.
PubMed IF 2.75 류마티스내과Abstract
Interleukin-8 (IL-8), a CXC chemokine that recruits and activates inflammatory cells, plays a critical role in the pathogenesis of Behcet's disease (BD). To investigate the association of the genetic polymorphism of IL-8 and BD, we genotyped IL-8 -845 T/C, -738 T/A, -353 A/T, -251 A/T, +293 G/T, +678 T/C and receptors CXCR-1 +2607 G/C and CXCR-2 +785 C/T polymorphisms in 119 Korean patients with BD and 119 age- and sex-matched healthy blood donors. Then, single nucleotide polymorphisms (SNPs) and haplotypes were analyzed between patients and controls. There were no SNPs associated with BD. However, the frequency of haplotype TAT inferred from SNPs, IL-8 -353 A/T, -251 A/T and +678 T/C, was significantly higher in patients with BD than controls (5.9 vs 0.0%, P = 0.0001), as was haplotype ATC (6.7 vs 0.0%, P < 0.0001). The haplotype difference was still valid in human leukocyte antigen-B51-negative subjects. In conclusion, we found a significant difference in the distribution of IL-8 gene haplotypes between patients with BD and healthy controls. These results suggest that the genetic polymorphisms of proinflammatory chemokine IL-8 can contribute to the pathogenesis of BD.
- 1732007
제1저자 이종열 · 교신저자 김주성
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Simvastatin inhibits NF-kappaB signaling in intestinal epithelial cells and ameliorates acute murine colitis.Int Immunopharmacol. 2007;7(2):241-8.
PubMed IF 5.6 소화기내과Abstract
Statins, HMG-CoA reductase inhibitors exert pleiotropic anti-inflammatory properties in vitro and in vivo, and are associated with the risk reduction of colorectal cancer. It remains unknown, however, whether statin is effective for the treatment of inflammatory bowel disease (IBD). Therefore, we investigated anti-inflammatory effects of simvastatin on intestinal epithelial cells (IEC) and on an experimental murine colitis model, and elucidated its molecular mechanisms. Simvastatin (50 micro M) significantly inhibited TNF-alpha-induced IL-8 gene expression in COLO 205 cells. Simvastatin (50 micro M) blocked TNF-alpha-induced NF-kappaB transcriptional activity, IkappaB phosphorylation/degradation and DNA binding activity of NF-kappaB. Administration of simvastatin significantly reduced the severity of dextran sulfate sodium (DSS)-induced murine colitis as assessed by body weight, colon length, DAI, and histology in a dose-dependent manner. These results suggest that simvastatin inhibits proinflammatory gene expression by blocking NF-kappaB signaling in IEC, and attenuates DSS-induced acute murine colitis. Simvastatin could be a potential agent for the treatment of IBD.
- 1722007
제1저자 김희정 · 교신저자 임재준
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Lack of association between the microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene and bronchiectasis among Koreans.Respirology. 2007;12(1):49-53.
PubMed IF 7.2 호흡기내과Abstract
BACKGROUND AND OBJECTIVE The genetic factors for the development of bronchiectasis are not well understood in most patients. The aim of this study was to elucidate the possible association between bronchiectasis and guanine-thymine (GT) repeat polymorphism in intron 2 of the human Toll-like receptor 2 (TLR2), which has a crucial role in adaptive as well as innate immunity.
METHODS A total of 194 patients with bronchiectasis and the same number of age- and gender-matched healthy blood donors were prospectively enrolled. The numbers of GT repeats were determined by PCR and gene scans. For further analysis, the alleles were classified into three subclasses: 12-16 GT repeats, short alleles (S allele); 17-22 repeats, medium-length alleles (M allele); and 23-27 repeats, long alleles (L allele).
RESULTS The overall distribution of alleles was not different between patient and control groups (P = 0.71). In addition, the frequencies of genotypes including short alleles were not different between patient and control groups (P = 0.92). Extent of bronchiectasis (P = 0.92) and bacterial colonization (P = 0.48) were not associated with any subclass genotype.
CONCLUSIONS Alleles and genotype including the shorter GT repeats in intron 2 of the TLR2, were not associated with the development, extent and bacterial colonization of bronchiectasis in Koreans.
- 1712007
제1저자 김성한 · 교신저자 오명돈
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The persistence of humoral and cellular immunities more than three decades after smallpox vaccination.Clin Microbiol Infect. 2007;13(1):91-3.
PubMed IF 8.7 감염내과Abstract
This study assessed the persistence of humoral (neutralising antibody titre to vaccinia virus) and cellular (immediate vaccinia-specific interferon (IFN)-gamma-producing T-cell) immunities to smallpox in a Korean population. Individuals who were vaccinated 25-60 years previously had higher neutralising antibody titres (geometric mean titre (GMT) 13.7; 95% CI 11.0-17.2) than vaccinia-naive individuals (GMT 6.7; 95% CI 5.5-8.0; p <0.001). However, there was no significant difference in cellular immunity between individuals vaccinated previously and vaccinia-naive individuals, and only 15% of the individuals vaccinated previously displayed an immediate IFN-gamma-producing effector-memory response in ELISPOT assays.
- 1702007
제1저자 김재현 · 교신저자 박경수
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Influence of strain and age differences on the yields of porcine islet isolation: extremely high islet yields from SPF CMS miniature pigs.Xenotransplantation. 2007;14(1):60-6.
PubMed IF 3.8 내분비대사내과Abstract
BACKGROUND Porcine pancreas is a potential source of material for islet xenotransplantation. However, the difficulty in isolating islets, because of their fragility and the variability of isolation outcome in donor age and breed, represents a major obstacle to porcine islet xenotransplantation. In this study, we compared the islet isolation yield of specific pathogen-free (SPF) Chicago Medical School (CMS) miniature pigs with that of another miniature pig breed and market pigs from a local slaughterhouse.
METHODS Nine adult CMS miniature (ACM) pigs (>12 months), six young CMS miniature (YCM) pigs (6-7 months), four adult Prestige World Genetics (PWG) miniature (APM) pigs (>12 months), and 13 adult market (AM) pigs from a local slaughterhouse were used for islet isolation.
RESULTS The islet yield per gram of pancreas from ACM pigs (9589 +/- 2823 IEQ/g) was significantly higher than that from APM pigs (1752 +/- 874 IEQ/g, P < 0.05), AM pigs (1931 +/- 947 IEQ/g, P < 0.05), or YCM pigs (3460 +/- 1985 IEQ/g, P < 0.05). Isolated islets from ACM pigs were significantly larger than those from AM pigs or YCM pigs. The in vitro and in vivo function of isolated islets showed no difference among experimental groups. The pancreases of ACM pigs contained higher mean islet volume density percentages and larger size of islets than those of AM or APM pigs.
CONCLUSIONS We isolated extremely high yields of well-functioning islets from ACM pigs bred under SPF conditions. SPF CMS miniature pigs should be one of the best porcine islet donors for clinical porcine islet xenotransplantation.
- 1692007
제1저자 김형관 · 교신저자 손대원
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Assessment of left ventricular rotation and torsion with two-dimensional speckle tracking echocardiography.J Am Soc Echocardiogr. 2007;20(1):45-53.
PubMed IF 8.3 순환기내과Abstract
BACKGROUND Speckle tracking echocardiography (STE) has a unique feature of angle independence and, thus, may provide a powerful means of assessing left ventricular (LV) torsion (LVtor). The aims of this study were to assess: (1) the feasibility of 2-dimensional STE in the measurement of LVtor; and (2) the relationship of LVtor with age and conventional echocardiographic parameters.
METHODS We consecutively recruited 160 healthy volunteers. After obtaining conventional echocardiographic parameters, apical and basal short-axis rotations were assessed with STE. LVtor was defined as the net difference between rotation angles in the two short-axis planes normalized for LV longitudinal length.
RESULTS Reliable LVtor measurement was possible only in 56 volunteers (35%). This low feasibility was largely a result of the failure to obtain reliable basal rotation values. In 56 volunteers who were finally enrolled in this study, a significant correlation was found between LV ejection fraction and LVtor (r = 0.56, P < .001) and this correlation was attributed to apical (r = 0.47, P < .001) but not basal (P = .14) rotation. There was no significant change in LVtor with aging. However, initial counterclockwise motion (r = -0.51, P = .001) and its interval (r = -0.44, P = .001) in the basal rotation gradually decreased with aging, and correlated with early transmitral inflow velocity (r = 0.44 and 0.49, respectively) and its deceleration time (r = -0.43 and -0.48, respectively) (all P < .001). In contrast, such correlations were not found for initial clockwise motion and its interval in the apical rotation.
CONCLUSIONS Currently, STE has limited feasibility in the measurement of LVtor. There was no significant age-related change in LVtor. In LV rotations, basal rotation was affected by the age-related changes in the LV early diastolic filling, whereas apical rotation was mainly related to LV systolic performance.
- 1682007
제1저자 조요한 · 교신저자 윤성수
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Pharmacokinetics and tolerability of intravenous busulfan in hematopoietic stem cell transplantation.Clin Transplant. 2007;21(3):417-22.
PubMed IF 1.8 혈액종양내과Abstract
Intravenous (IV) busulfan has been developed to overcome variable absorption of oral busulfan and tested in several trials. We tested its pharmacological properties and tolerability in 16 Korean stem cell transplantation (SCT) patients. IV busulfan was administered at 0.8 mg/kg every six h for a total of 16 doses (days -7 to -4), which was followed by cyclophosphamide administration at 60 mg/kg every 24 h for two d (days -3 and -2). The median AUC(inf) values (at the first dose) and AUC(ss) (at the steady state) were 1060.4 microM.min (range: 511.1-1812.7) and 1092.5 microM.min (range: 539.7-1560.8) respectively. All patients had an AUC(inf) of <1500 microM.min at the first dose, and 13 of the 16 (81.3%) maintained AUC(ss) levels between 800 and 1500 microM.min. Thirteen of 16 patients showed successful engraftments but four patients (25%) developed hepatic VOD (two of which were fatal), three of whom had advanced disease at the time of SCT. Overall, pharmacokinetics of IV busulfan in our SCT patients appeared comparable with those observed in other study. However, hepatic VOD was a major morbidity in patients with advanced disease.
- 1672007
제1저자 윤탁 · 교신저자 윤성수
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Non-myeloablative allogeneic stem cell transplantation for metastatic renal cell carcinoma.Clin Transplant. 2007;21(3):337-43.
PubMed IF 1.8 혈액종양내과Abstract
Between 1999 and 2004, 11 patients with metastatic renal cell carcinoma (RCC) underwent non-myeloablative stem cell transplantation (NST) with conditioning using fludarabine-based regimens in two institutions of Korea. Among 11 patients, only one patient showed partial response (response rate: 9%), three showed stable disease, and six progressive disease. Three patients developed acute graft-versus-host disease (GVHD), and among them, one developed grade III acute GVHD which caused early death at day 60 after transplantation, and this patient showed partial response at day 30. Six patients developed chronic GVHD, three limited, and three extensive GVHD, respectively. Survival after one yr was 18% in transplanted patients. Median overall survival for entire cohort was 4.3 months. Eight patients died from progressive disease and three (27%) from treatment-related mortality. Only one patient survived 51.2 months after NST with slowly progressive disease. This patient received donor lymphocyte infusion three times after NST and achieved complete donor chimerism. NST does not lead to durable response and prolonged overall survival in the majority of patients with RCC in our series.
- 1662007
제1저자 이효석 · 교신저자 이효석
Liver transplantation for hepatocellular carcinoma beyond the Milan criteria: the controversies continue.Dig Dis. 2007;25(4):296-8.
PubMed IF 2.4 소화기내과Abstract
Liver transplantation has now become a favored option for patients with early-stage hepatocellular carcinoma (HCC) with or without impaired hepatic function as a complication of underlying cirrhosis. To overcome the persistent donor organ shortage, the use of adult-to-adult living donor liver transplantation (LDLT) has recently increased, especially in Asian countries. In the use of LDLT, several controversies remain including the safety of living donation and expanding the current Milan criteria. Most physicians agree that criteria for transplanting patients with HCC should be expanded beyond the Milan criteria because the Milan criteria miss a number of patients who may benefit from LDLT; however, the expanded criteria proposed were different (the size and number of HCCs and the biologic markers) from one center to the other. When we consider LDLT as a treatment option for patients with HCC, donor safety should be kept in mind first, and the wishes of both patient and donor should be weighed against the potential (if small) risk for the donor. In contrast to deceased donor liver transplantation, the benefit of LDLT is better appreciated in terms of gain in life expectancy than in terms of survival when the wishes of both patient and donor outweigh the donor risk. Further research on the predictors of benefit of LDLT to HCC patients other than the size and number of HCC such as molecular profiling of HCC are necessary to finally reach a consensus.
- 1652007
제1저자 이윤종 · 교신저자 송영욱
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Serum galectin-3 and galectin-3 binding protein levels in Behçet's disease and their association with disease activity.Clin Exp Rheumatol. 2007;25(4 Suppl 45):S41-5.
PubMed IF 3.2 류마티스내과Abstract
OBJECTIVE To determine the serum levels of galectin-3 (Gal-3) and galectin-3 binding protein (G3BP) and to evaluate the associations between clinical features and these levels in patients with Behçet's disease (BD).
METHODS Fifty patients with BD (mean age 40.6 +/- SEM 1.4 years; 21 males, 29 females; 26 active and 24 inactive patients), 20 patients with rheumatoid arthritis (RA), and 20 patients with systemic lupus erythematosus (SLE) were enrolled. Clinical features of BD patients including BD activity and severity over the previous 4 weeks were reviewed and serum levels of Gal-3 and G3BP were determined using enzyme-linked immunosorbent assays (ELISA).
RESULTS Serum Gal-3 levels were significantly higher in total BD patients than in healthy controls (mean +/- SEM, 10.68 +/- 0.93 versus 7.59 +/- 0.48 ng/mL; p = 0.0042 by Student's t-test), and active BD patients had significantly higher levels of serum Gal-3 than inactive patients and controls (13.08 +/- 1.53 in active BD, 8.08 +/- 0.71 ng/mL in inactive BD; p = 0.000039 by one way ANOVA). Although mean G3BP serum levels were not different in total BD patients and controls, active BD patients (6806.63 +/- 468.58 ng/mL) had higher G3BP levels than controls (5421.05 +/- 286.02 ng/mL; p = 0.031 by one way ANOVA). Additionally, serum Gal-3 significantly increased in patients with RA (p = 0.019 by t-test) and SLE (p = 0.00069) and G3BP increased in patients with SLE (p = 0.000012), compared to those in healthy controls. When we analyzed for associations with clinical features over the previous 4 weeks, Gal-3 was associated with orogenital ulcers (p = 0.036 by t-test) and time elapsed from symptom onset (p = 0.032, Pearson's coefficient = 0.314). Serum concentrations of Gal-3 (p = 0.013) and G3BP (p = 0.032) were positively correlated with the BD severity score for the previous 4 weeks. Gal-3 levels were significantly correlated with TNF-alpha (p = 0.048, Pearson's coefficient = 0.281) and G3BP levels were correlated with levels of C-reactive protein (p = 0.021, Pearson's coefficient = 0.329) in total BD patients. In multivariate analysis of all cytokines levels, only Gal-3 was significantly related to BD activity or severity for the previous 4 weeks.
CONCLUSION These results suggest that serum levels of Gal-3 and G3BP are increased in active BD patients and Gal-3 can be a new biomarker indicating disease activity in BD although their increments are not disease-specific.
- 1642007
제1저자 이은봉 · 교신저자 송영욱
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Immunoglobulin GM and KM genotypes in Korean patients with systemic lupus erythematosus.Rheumatol Int. 2007;27(3):219-24.
PubMed IF 3.5 류마티스내과Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex deposition. We genotyped immunoglobulin allotypes of G1M (f,z), G2M (n+,n-), G3M (b,g) and KM (1,3) in 142 Korean patients with SLE and 200 healthy controls to investigate the role of the allotypes in SLE. The allele frequency of G1M (z) was significantly higher in patients with SLE as compared to the healthy controls (94.6% vs. 84.3%, corrected P = 0.0004, OR 3.30, 95% CI 1.71-6.88). The frequency of G2M (n-) allele was also higher in patients with SLE (95.3% vs. 88.3%, corrected P = 0.008, OR = 2.71, 95% CI 1.38-5.72). Distribution of the tested allele frequencies for G3M and KM were not different between the patients and controls. In the respect of antibody production, there was increased genotype frequency of G1M (z/z) in anti-Sm(-) SLE (P = 0.023 vs. control, P = 0.042 vs. anti-Sm (+) SLE). In conclusion, particular genotypes at G1M (f,z) and G2M (n+,n-) loci are significantly associated with SLE. These immunoglobulin genes may contribute to the etiology of SLE and production of autoantibodies.
- 1632007
제1저자 조재현 · 교신저자 김남중
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Bacteremia is a prognostic factor for poor outcome in spontaneous bacterial peritonitis.Scand J Infect Dis. 2007;39(8):697-702.
PubMed IF 1.56 감염내과Abstract
We performed a retrospective study to determine the influence of bacteremia on the mortality of patients with spontaneous bacterial peritonitis (SBP), a major complication of liver cirrhosis. Patients with SBP with identified pathogens from ascites and/or blood were analyzed by retrospective review of clinical and laboratory records in a university hospital in Korea for 3 y and classified into the bacteremic and non-bacteremic groups. The underlying liver function was determined by model for end-stage liver disease (MELD) score. Microbiological response rate, ascites polymorphonuclear leukocyte (PML) count reduction rate, and SBP-related mortality were compared between the 2 groups. To identify the independent risk factors of mortality, a multiple logistic regression model was used to control for the confounders. A total of 189 patients was enrolled in the study. Among 189 patients, 110 (58.2%) were bacteremic, and 79 (41.8%) non-bacteremic. Escherichia coli was the most common etiologic organism, followed by Klebsiella pneumoniae. MELD scores, microbiological response rate (82.6% vs 88.6%, p=0.295), and ascites PML count reduction rate (33.2% vs 44.8%, p=0.479) were not different between the bacteremic and non-bacteremic group. However, the SBP-related mortality rate of the bacteremic group was significantly higher than that of the non-bacteremic group (37.3% vs 12.7%, p<0.001). Bacteremia (OR=2.86: 95% CI 1.06-7.74, p=0.038), APACHE II score (OR=1.20: 95% CI 1.10-1.31, p<0.001), MELD score (OR=1.07: 95% CI 1.01-1.31, p=0.016) and microbiological no response (OR=5.51: 95% CI 1.82-16.72, p=0.003) were independent risk factors of SBP-related mortality.
- 1622007
제1저자 천재희 · 교신저자 김주성
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Risk factors for upper gastrointestinal rebleeding in critically ill patients.Hepatogastroenterology. 2007;54(75):766-9.
PubMed IF 0.76 소화기내과Abstract
BACKGROUND/AIMS To determine the risk factors for rebleeding after upper gastrointestinal bleeding in critically ill patients.
METHODOLOGY We retrospectively analyzed the medical records of consecutive 60 patients undergoing bedside esophagogastroduodenoscopy between January 2000 and December 2004 for upper gastrointestinal bleeding that developed while in the ICU.
RESULTS Eight of the 60 patients died within 7 days after initial bleeding and two of the eight died due to upper gastrointestinal bleeding. Seven-day rebleeding rate was 34.6% (18/52). An additional 7 patients died within 30 days, none of whom died of upper gastrointestinal bleeding. Thirty-day rebleeding rate was 51.1% (23/45). In multiple logistic regression using selected significant variables, anemia (Hb < 9.0g/dL), and hypoalbuminemia (albumin < 3.0g/dL) for 7-day rebleeding, and hypoxia (PaO2 < 80mmHg), anemia (Hb < 9.0g/dL), and units of blood transfused (> or = 3) for 30-day rebleeding were the significant independent risk factors in critically ill patients.
CONCLUSIONS The results of this study suggest that underlying patients' conditions or the severity of initial upper gastrointestinal bleeding affect rebleeding in the ICU setting. Adequate general ICU care including the prevention of initial bleeding and correction of hypoxia, anemia, and hypoalbuminemia after bleeding could reduce the rebleeding risk.
- 1612007
제1저자 곽금연 · 교신저자 이효석
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Lack of association between serum leptin levels and hepatic steatosis, fibrosis or response to antiviral therapy in Korean chronic hepatitis C patients.Hepatogastroenterology. 2007;54(75):844-8.
PubMed IF 0.76 소화기내과Abstract
BACKGROUND/AIMS Leptin has been recently implicated in the development of hepatic steatosis and fibrosis in chronic hepatitis C (CHC) infection. The serum levels of leptin are known to be strongly affected by anthropometric parameters such as body mass index (BMI) and total body fat, which show differences between races or ethnicities. In this study, we examined whether serum leptin levels are correlated with clinical, virological, and histological features, and with response to antiviral therapy in Korean CHC patients.
METHODOLOGY We evaluated correlations between serum leptin level and age, sex, BMI, fasting glucose, alanine aminotransferase, genotype, hepatitis C virus RNA titer, steatosis, fibrosis, and response to antiviral therapy after 24 weeks completing 24 weeks of interferon-alpha based therapy in 47 Korean CHC patients.
RESULTS Of the variables examined, only female sex and a BMI > 25kg/m2 were identified as independent variables related to a higher leptin level by multivariate analysis. Baseline leptin levels and leptin changes before/after antiviral therapy were not correlated with response to therapy.
CONCLUSIONS In Korean CHC patients, serum leptin levels were found to be correlated with anthropometric parameters, but not with virological or histological features. In addition, serum leptin levels did not predict response to antiviral therapy.
- 1602007
제1저자 오진영 · 교신저자 이춘택
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Clinical significance of a solitary ground-glass opacity (GGO) lesion of the lung detected by chest CT.Lung Cancer. 2007;55(1):67-73.
PubMed IF 5.3 호흡기내과Abstract
Ground-glass opacity (GGO) attracts attention because of the possibility of early lung cancer. However, some lesions are reduced in size or disappear at follow-up. This study was designed to explore the natural history of solitary GGO, to determine the prevalence of malignancy and to identify factors predictive of benignity or malignancy. Solitary and focal GGO lesions [pGGO (p=pure) and mGGO (m=mixed) based on the presence of a solid component] of less than 3 cm were included. Lesions of less than 1cm were followed up by chest HRCT 3 months later and lesions over 1cm were investigated by percutaneous needle biopsy (PCNB). One hundred and eighty-six patients (69 pGGO and 117 mGGO) were enrolled. Of the 69 pGGO lesions, 7 were diagnosed as pre-malignant or malignant lesions, 3 as benign lesions and 26 pGGO lesions (37.6%) were reduced or disappeared (transient lesions) at follow-up chest HRCT. The other 33 lesions showed no significant change during follow-up. Thus, the probability of malignancy in pGGO was 7/36 (19.4%). On the other hand, of the 117 mGGO lesions, 26 were found to be malignant, 3 were diagnosed as benign and 57 lesions (48.7%) were reduced or had disappeared at follow-up chest HRCT. The other 31 lesions showed no change during follow-up, and thus the probability of malignancy in mGGO was 26/86 (30.2%). A female sex and a spiculated mGGO border were found to be related with malignancy. However, a high blood eosinophil count was strongly associated with regressing or transient mGGO, suggesting that pulmonary infiltrate with eosinophilia (PIE) might have been responsible. We recommend short-term follow-up by chest HRCT be conducted for mGGO lesions in the presence of high eosinophilia--regardless of lesion size.
- 1592007
제1저자 김인호 · 교신저자 박선양
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Polymorphisms of the methylenetetrahydrofolate reductase gene and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation.Ann Hematol. 2007;86(1):41-8.
PubMed IF 2.3 혈액종양내과Abstract
To evaluate whether the C677T and A1298C polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) are related to the toxicity of methotrexate (MTX) used in allogeneic stem cell transplantation, we performed association analysis between these genetic polymorphisms and the clinical outcomes of patients treated using human leukocyte antigen-matched sibling stem cell transplantation. Patients (n=72) with hematological malignancy or aplastic anemia were given a short course of MTX as a graft-versus-host disease prophylaxis. Patients with the 677TT genotype showed higher total bilirubin levels (677TT vs 677CT vs 677CC, 14.5 vs 8.6 vs 3.8 mg/dl, respectively; p=0.07) and higher aspartic transaminase levels (677TT vs 677CT vs 677CC, 678.9 vs 156.6 vs 111.8 IU/l; p=0.04). Platelet recovery to 20,000/mul was slower for patients with the 677TT genotype than for patients with other genotypes (677TT, 59 days; 677CT, 26 days; 677CC, 26 days; p=0.0075). The influences of the C677T polymorphism on treatment-related mortality (TRM) were also analyzed. One-year cumulative TRMs for patients with the TT genotype and the other genotypes were 66 and 30% (p=0.04) and their respective 1-year overall survivals were 30 and 56% (p=0.11). No association was observed between the A1298C polymorphism and clinical outcome for any of the different genotypes. Therefore, patients at high risk of developing hepatic toxicity and with a poor likelihood of survival could be selected by genotyping MTHFR C677T before allogeneic stem cell transplantation.
- 1582006
제1저자 박병래 · 교신저자 이효석
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Association of common promoter polymorphisms of MCP1 with hepatitis B virus clearance.Exp Mol Med. 2006;38(6):694-702.
PubMed IF 17.5 소화기내과Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant cancers closely associated with chronic infection by the hepatitis B virus (HBV) or the hepatitis C virus (HCV) throughout the world. In this study, the genetic associations of 20 known polymorphisms in eight candidate genes, including angiotensinogen (AGT), cadherin 1 (CDH1), cyclooxygenase 2 (COX2), monocyte chemotactic protein-1 (MCP1), multidrug resistance 1 (MDR1), chemokine ligand 5 (RANTES), thrombospondin 2 (THBS2), and thrombospondin 4 (THBS4), were analyzed in a large chronic hepatitis B cohort (n=1,095) recruited from the Korean population. In addition, three polymorphisms in chemokine receptor 4 (CXCR4) and vimentin (VIM) identified in this study were also genotyped. Using logistic regression analysis controlling possible confounding factors, one common (freq.=0.367) promoter polymorphism of MCP1 (MCP1-2518G>A) among analyzed polymorphisms was significantly associated with clearance of HBV infection. The frequency of homozygotes for the MCP1-2518A allele (MCP1-2518A/A) among chronic hepatitis B virus (HBV) carrier patients was significantly higher than that among spontaneously recovered (SR) subjects (17.7% vs. 10.4%)(OR=1.78, P=0.004). Our findings imply a plausible explanation for the contribution of host genetic determinants to the variable outcome of HBV infection, which might provide valuable information for future genetic study in this area.
- 1572006
제1저자 최창민 · 교신저자 임재준
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The role of TST in the diagnosis of latent tuberculosis infection among military personnel in South Korea.Int J Tuberc Lung Dis. 2006;10(12):1342-6.
PubMed IF 3.6 호흡기내과Abstract
BACKGROUND The rapid and accurate diagnosis of latent tuberculosis infection (LTBI) is crucial in military settings because military personnel live in crowded circumstances and are of an age group with a high incidence of tuberculosis (TB). We tried to elucidate whether the tuberculin skin test (TST) accurately reflects the risk of TB infection among military personnel, in a setting of intermediate TB prevalence and where bacille Calmette-Guérin (BCG) vaccination is mandatory.
METHODS A multi-stage cluster survey was conducted among military personnel in South Korea. Participants were grouped according to their risk of TB infection: Group 1, no identifiable risk of TB; Groups 2 and 3, recent casual (Group 2) or close (Group 3) contact with smear-positive TB patients.
RESULTS Of 1045 participants, 857 (82.0%) had been BCG-vaccinated. The odds ratio (OR) of a positive TST (10 mm cut-off) for Group 2 (n = 184) and Group 3 (n = 83) compared with Group 1 (n = 778) were 0.95 (95%CI 0.67-1.38) and 1.7 (95%CI 1.06-2.70), respectively (P value for trend 0.16).
CONCLUSIONS The TST does not accurately reflect the risk of LTBI among young military personnel in a setting where there is intermediate TB prevalence and extensive BCG coverage.
- 1562006
제1저자 천재희 · 교신저자 김주성
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Plant sterol guggulsterone inhibits nuclear factor-kappaB signaling in intestinal epithelial cells by blocking IkappaB kinase and ameliorates acute murine colitis.Inflamm Bowel Dis. 2006;12(12):1152-61.
PubMed IF 5.5 소화기내과Abstract
BACKGROUND/AIMS The plant sterol guggulsterone has been shown to have anti-inflammatory properties. It remains unknown, however, whether guggulsterone is effective for the treatment of inflammatory bowel disease (IBD). Therefore, we investigated anti-inflammatory effects of guggulsterone on intestinal epithelial cells (IEC) and on experimental murine colitis models and elucidated its molecular mechanisms.
METHODS Human Caco-2 cells and rat non-transformed IEC-18 cells were stimulated with interleukin (IL)-1beta or lipopolysaccharide (LPS) with or without guggulsterone. The effects of guggulsterone on nuclear factor (NF)-kappaB signaling in IEC were examined by intercellular adhesion molecule (ICAM)-1 real-time reverse-transcription polymerase chain reaction, NF-kappaB transcriptional activity assay, Western blotting for IkappaB phosphorylation/degradation, electrophoretic mobility shift assay, and in vitro IkappaB kinase (IKK) assay. For in vivo study, dextran sulfate sodium (DSS)-treated mice were fed with or without guggulsterone. Colitis was quantified by disease activity index and evaluation of macroscopic and microscopic findings. Phosphorylation of IkappaB and IKK in colon mucosa was assessed by Western blotting and immunohistochemistry.
RESULTS Guggulsterone significantly inhibited LPS- or IL-1beta-induced ICAM-1 gene expression, NF-kappaB transcriptional activity, IkappaB phosphorylation/degradation, and NF-kappaB DNA binding activity in IEC. Moreover, guggulsterone strongly blocked IKK activity. Administration of guggulsterone significantly reduced the severity of DSS-induced murine colitis as assessed by clinical disease activity score, colon length, and histology. Furthermore, tissue upregulation of IkappaB and IKK phosphorylation induced by DSS was attenuated in guggulsterone-treated mice.
CONCLUSION Guggulsterone blocks NF-kappaB signaling pathway by targeting IKK complex in IEC and attenuates DSS-induced acute murine colitis, which suggests that guggulsterone could be an attractive therapeutic option in the treatment of IBD.
- 1552006
제1저자 곽금연 · 교신저자 윤정환
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Lysophosphatidylcholine suppresses apoptotic cell death by inducing cyclooxygenase-2 expression via a Raf-1 dependent mechanism in human cholangiocytes.J Cancer Res Clin Oncol. 2006;132(12):771-9.
PubMed IF 3.3 소화기내과Abstract
PURPOSE The high incidence of biliary tract carcinoma in patients with anomalous pancreaticobiliary ductal junction (APBDJ) implicates that a compositional alteration in bile may contribute to the genesis of this cancer. Lysophosphatidylcholine (LPC) is generated in the bile of these patients. Given the role of cyclooxygenase-2 (COX-2) in biliary tract carcinogenesis, we postulated that LPC induces COX-2 in cholangiocytes.
METHODS The effect of LPC on COX-2 expression in cholangiocytes was evaluated by immunoblot analysis, real-time PCR and reporter gene assay. Apoptosis was induced by TRAIL treatment, and quantified using DAPI staining.
RESULTS Lysophosphatidylcholine increased COX-2 protein expression in cholangiocytes in a concentration- and time-dependent manner. LPC-induced Raf-1 activation was responsible for this COX-2 induction. Accordingly, LPC increased COX-2 mRNA levels in a Raf-1 dependent manner by stabilizing COX-2 mRNA. Finally, LPC attenuated TRAIL-mediated apoptosis through a COX-2/PgE2 dependent mechanism.
CONCLUSIONS Collectively, these results implicate that LPC inhibits cholangiocyte apoptosis by inducing COX-2 expression via a Raf-1 dependent mechanism. This anti-apoptotic signaling may participate in biliary tract carcinogenesis in APBDJ patients, and therefore, its interruption may be a viable chemopreventative strategy.
- 1542006
제1저자 김연수 · 교신저자 김연수
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Distinctive role of donor strain immature dendritic cells in the creation of allograft tolerance.Int Immunol. 2006;18(12):1771-7.
PubMed IF 3.4 신장내과Abstract
Dendritic cells (DCs) are pivotal antigen-presenting cells and serve a unique role in initiating immunity. To test the hypothesis that pre-immunization of recipient with certain DC subsets of donor origin can influence graft outcome, we have studied the effects of immunization with allogeneic CD4(+)CD8(-)CD11c(+) dendritic cell (CD4(+)DC) and CD4(-)CD8(+)CD11c(+) dendritic cell (CD8(+)DC) on the allograft response. Although both immature CD4(+)DC and CD8(+)DC subsets from DBA/2 were able to prime naive allogeneic C57BL/6 (B6) T cells in mixed lymphocyte reaction (MLR), CD8(+)DC exerted more vigorous alloimmune responses than CD4(+)DC did. Also, CD4(+)DC-driven allogeneic T cell response was attenuated more significantly by anti-CD154 mAb than CD8(+)DC-driven response. Consistent with the MLR results, combined pre-treatment with CD4(+)DC, but not CD8(+)DC, plus anti-CD154 mAb produced donor strain-specific long-term graft survival and induced tolerance while treatment with CD8(+)DC plus anti-CD154 mAb created minimal prolongation of allograft survival in a pancreas islet transplant model (DBA/2-->B6). The beneficial effects exerted by CD4(+)DC and anti-CD154 mAb pre-treatment were correlated with T(h)1 to T(h)2 immune deviation and with the amplified donor-specific suppressive capacity by recipient CD4(+)CD25(+) T cells. These findings highlight the capacity of CD4(+)DC to modulate alloimmune responses, and suggest therapeutic approaches for the induction of donor-specific tolerance.
- 1532006
제1저자 이세원 · 교신저자 임재준
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The prevalence and evolution of anemia associated with tuberculosis.J Korean Med Sci. 2006;21(6):1028-32.
PubMed IF 3.2 호흡기내과Abstract
Tuberculosis (TB) may produce abnormalities in the peripheral blood, including anemia. However, the evolution of TB-associated anemia with short-term combination anti-TB chemotherapy has not been well elucidated. The aim of this study was to characterize TB-associated anemia by clarifying its prevalence, characteristics, and evolution, through involving large numbers of patients with TB. The medical records of adult patients with TB diagnosed between June 2000 and May 2001 were reviewed. Among 880 patients with TB, 281 (31.9%) had anemia on diagnosis of TB, however, the hemoglobin concentration was less than 10 g/dL in only 45 patients (5.0%). Anemia was more frequently associated with the female and old age. Good treatment response, young age (< or =65 yr-old) and initial high hemoglobin were the predictive factor for resolution of anemia. In 202 patients with anemia (71.9%), anemia was normocytic and normochromic. During or after anti-TB treatment, anemia was resolved in 175 (64.6%) out of 271 patients without iron intake. The mean duration of resolution from the initiation of anti-TB treatment was 118.8+/-113.2 days. In conclusion, anemia is a common hematological abnormality in patients with TB and close observation is sufficient for patients with TB-associated anemia, because TB-associated anemia is usually mild and resolves with anti-TB treatment.
- 1522006
제1저자 이은영 · 교신저자 송영욱
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Tramadol 37.5-mg/acetaminophen 325-mg combination tablets added to regular therapy for rheumatoid arthritis pain: a 1-week, randomized, double-blind, placebo-controlled trial.Clin Ther. 2006;28(12):2052-60.
PubMed IF 3.7 류마티스내과Abstract
OBJECTIVE This study evaluated the efficacy and tolerability of tramadol 37.5-mg/acetaminophen 325-mg combination tablets (tramadoUAPAP) as add-on therapy in subjects with rheumatoid arthritis (RA) pain that was inadequately controlled by NSAIDs and disease-modifying antirheumatic drugs alone.
METHODS Subjects in this multicenter, double-blind trial were randomized in a 3:1 ratio to receive 1 tramadol/ APAP tablet TID or a matching placebo for 1 week. Stable doses of previous medications were continued during the study. The primary efficacy variable was the mean daily pain relief score over 1 week, measured on a 6-point scale (4 = complete; ' = a lot; 2 = some; 1 = a little; 0 = none; -1 = worse). Secondary outcomes included the mean daily pain intensity score, measured on a 100-mm visual analog scale (VAS) (from 0 mm = no pain to 100 mm = extreme pain); pain intensity and pain relief at day 7; subjects' and investigators' mean overall assessments of study drug, measured on a Likert scale (from 2 = very good to -2 = very poor); and subjects' assessments of 8 aspects of physical function (measured on the Health Assessment Questionnaire).
RESULTS Of 277 subjects randomized to treatment, 267 (201 tramadol/APAP, 66 placebo) were included in the intent-to-treat population. Mean (SD) daily pain relief scores at the end of 1 week were significantly greater in the tramadol/APAP group compared with the placebo group (1.04 [0.89] vs 0.78 [0.80], respectively; P = 0.037), and mean daily pain intensity scores at the end of 1 week were significantly lower (47.23 [19.96] vs 53.81 [16.59]; P = 0.018). Physical function at the end of 1 week did not differ significantly between tramadol/APAP and placebo. Two hundred seventy-two subjects (205 tramadol/APAP, 67 placebo) were evaluable for tolerability. One hundred thirty-three of these subjects had at least 1 adverse event. The incidence of adverse events was significantly higher in the tramadol/APAP group than in the placebo group (57.6% vs 22.4%; P < 0.001). Discontinuations due to adverse events occurred in 19.0% of the tramadol/APAP group and 3.0% of the placebo group (P = 0.001). Of 213 treatment-related adverse events in tramadol/APAP subjects, nausea (34.1%) was the most frequent, followed by dizziness (20.0%) and vomiting (15.6%). One serious adverse event--chest discomfort, nausea, and vomiting after taking study medication-occurred in a subject receiving tramadol/APAP The symptoms resolved 1 day after discontinuing tramadol/APAP.
CONCLUSIONS In this study, tramadol/APAP used as add-on therapy in subjects with symptomatic RA was associated with a significant improvement in pain relief and a significant reduction in pain intensity compared with placebo, with no improvement in physical function. Use of tramadol/APAP may be considered when analgesics are needed in addition to conventional NSAIDs and disease-modifying antirheumatic drugs in subjects with RA.
- 1512006
제1저자 이주희 · 교신저자 김태유
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Histone deacetylase inhibitor enhances 5-fluorouracil cytotoxicity by down-regulating thymidylate synthase in human cancer cells.Mol Cancer Ther. 2006;5(12):3085-95.
PubMed IF 6.9 혈액종양내과Abstract
Thymidylate synthase (TS) overexpression is a key determinant of 5-fluorouracil (5-FU) resistance in human cancer cells. TS is also acutely up-regulated with 5-FU treatment, and, thus, novel strategies targeting TS down-regulation seem to be promising in terms of modulating 5-FU resistance. Here, we report that histone deacetylase inhibitors can reverse 5-FU resistance by down-regulating TS. By using cDNA microarrays and validation experiments, we found that trichostatin A reduced the expression of both TS mRNA and TS protein. Cotreatment with trichostatin A and cycloheximide restored TS mRNA expression, suggesting that TS mRNA is repressed through new protein synthesis. On the other hand, TS protein expression was significantly reduced by lower doses of trichostatin A (50 nmol/L). Mechanistically, TS protein was found to interact with heat shock protein (Hsp) complex, and trichostatin A treatment induced chaperonic Hsp90 acetylation and subsequently enhanced Hsp70 binding to TS, which led to the proteasomal degradation of TS protein. Of note, combined treatment with low-dose trichostatin A and 5-FU enhanced 5-FU-mediated cytotoxicity in 5-FU-resistant cancer cells in accordance with TS protein down-regulation. We conclude that a combinatorial approach using histone deacetylase inhibitors may be useful at overcoming 5-FU resistance.
- 1502006
제1저자 강해연 · 교신저자 김나영
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Progression of atrophic gastritis and intestinal metaplasia drives Helicobacter pylori out of the gastric mucosa.Dig Dis Sci. 2006;51(12):2310-5.
PubMed IF 2.8 소화기내과Abstract
This study was performed to evaluate the implication of anti-H. pylori IgG positivity when CLOtest, histological test, and culture in the antrum and body are all negative, and to find out the specific disease category that is more affected by the hostile relationship of atrophic gastritis and intestinal metaplasia (IM) with H. pylori. Four hundred thirty-six patients (84 controls, 69 with duodenal ulcer, 96 with benign gastric ulcer, 43 with dysplasia, 144 with gastric cancer), who had not received any eradication therapy, were divided into three groups according to H. pylori test: CLOtest or histological H. pylori-positive group (group A; 294 cases), only anti-H. pylori IgG-positive group (group B; 62 cases), and anti-H. pylori IgG-negative group (group C; 80 cases). The grade of neutrophil and monocyte infiltration, atrophic gastritis, and IM was compared according to the updated Sydney system classification. Neutrophil and monocyte infiltrations were significantly severe in the group A. In contrast, the grade of atrophic gastritis and IM in the antrum was significantly higher in group B than the other two groups, A or C. When patients were divided according to the disease outcome in each group, the grade of IM in the body was statistically higher only in the patients with cancer or dysplasia in group B. These results suggest that anti-H. pylori IgG positivity with all negative invasive H. pylori tests represents past infection with H. pylori rather than a false negative, especially in the case of dysplasia and gastric cancer.
- 1492006
제1저자 이재정 · 교신저자 허대석
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Enhanced specificity of the p53 family proteins-based adenoviral gene therapy in uterine cervical cancer cells with E2F1-responsive promoters.Cancer Biol Ther. 2006;5(11):1502-10.
PubMed IF 5.7 혈액종양내과Abstract
p63 and p73, the p53 family proteins, are similar to p53 in many aspects: structural homology, transactivation of p53-downstream genes, and induction of apoptosis. Interestingly, they also differ from p53; in particular, they are not inhibited by viral oncoproteins such as HPV E6. This feature would be an advantage over p53 in HPV-associated cancers and therefore, we evaluated the therapeutic potentials of various p53 family proteins (p73alpha, p73beta, p63alpha and p63gamma) against HPV-infected cervical cancers. In clonogenic assay, exogenous expression of p73alpha, p73beta and p63gamma inhibited the colony formation of HPV-positive cervical cancer cells under G418- selection while p53 could not. Recombinant adenoviruses Ad/CMVp73alpha, Ad/CMVp73beta and Ad/CMVp63gamma induced potent apoptosis in all infected cervical cancers (CasKi, SiHa, HeLa, C33A, SNU682, SNU17, SNU1005, SNU703), irrespective of their HPV-infection status. Unfortunately however, Ad/CMVp73alpha, Ad/CMVp73beta, and Ad/CMVp63gamma inhibited also normal cells such as endothelial cells, fibroblasts, and keratinocytes thus, tumorspecific promoter was indispensable to the p53 family proteins-based therapy. Here we report a stringent tumor killing by p73beta in combination with ESM6, a synthetic promoter targeting the DNA tumor virusassociated cancers. Recombinant adenoviruses encoding p73beta by ESM6 (Ad/ESM6p73beta and Ad/ESM6p73bENH) expressed p73beta and induced apoptosis only in the cancer cells but not in normal cells. Collectively, we suggest that the p53 family proteins are potent therapeutic agents for HPV-associated uterine cervical cancers and ESM6 mediated expression of the p53 family proteins would be a safe and strong tumor targeting strategy.
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